Revision as of 17:20, 30 January 2020

Section editor
	J.C. Villasboas Bisneto, MD Mayo Clinic Rochester, MN

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108 regimens on this page 164 variants on this page

Guidelines

ESMO

2015: Tilly et al. Diffuse large B-cell lymphoma (DLBCL): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Older

2013: Ghielmini et al. ESMO Guidelines consensus conference on malignant lymphoma 2011 part 1: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL) PubMed

NCCN

NCCN Guidelines - B-cell Lymphomas

Untreated, pre-phase

Vincristine & Prednisone

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Regimen variant #1, PO vincristine

Study	Evidence
Peyrade et al. 2016 (LYSA LNH09-7B)	Phase II

Chemotherapy

Vincristine (Oncovin) 1 mg PO once on day -7
Prednisone (Sterapred) 60 mg PO once per day on days -7 to -4

7-day course

Subsequent treatment

O-miniCHOP

Regimen variant #2, IV vincristine

Study	Evidence
Pfreundschuh et al. 2004 (NHL-B1)	Non-randomized portion of RCT
Pfreundschuh et al. 2004 (NHL-B2)	Non-randomized portion of RCT
Pfreundschuh et al. 2008 (RICOVER-60)	Non-randomized portion of RCT
Pfreundschuh et al. 2014 (SMARTE-R-CHOP-14)	Phase II

Recommended in NHL-B1 and NHL-B2 "to improve the performance status of patients and to ameliorate side-effects of the first chemotherapy cycle." Mandated in RICOVER-60 and SMARTE-R-CHOP-14. Note: NHL-B1 gave the option of a 5 to 7 day course of prednisone.

Chemotherapy

Vincristine (Oncovin) 1 mg IV once (day not specified)
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 7

7-day course

Subsequent treatment

NHL-B1 and NHL-B2: CHOP versus CHOP-14 versus CHOEP-14 versus CHOEP-21
RICOVER-60: CHOP-14 versus R-CHOP-14
SMARTE-R-CHOP-14: R-CHOP-14

References

NHL-B1: Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rudolph C, Reiser M, Hossfeld DK, Metzner B, Hasenclever D, Schmitz N, Glass B, Rübe C, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):626-33. Epub 2004 Feb 24. link to original article contains verified protocol PubMed
NHL-B2: Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rübe C, Rudolph C, Reiser M, Hossfeld DK, Eimermacher H, Hasenclever D, Schmitz N, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):634-41. Epub 2004 Mar 11. link to original article contains verified protocol PubMed
RICOVER-60: Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, Reiser M, Nickenig C, Clemens M, Peter N, Bokemeyer C, Eimermacher H, Ho A, Hoffmann M, Mertelsmann R, Trümper L, Balleisen L, Liersch R, Metzner B, Hartmann F, Glass B, Poeschel V, Schmitz N, Ruebe C, Feller AC, Loeffler M; German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 2008 Feb;9(2):105-16. link to original article contains verified protocol PubMed
SMARTE-R-CHOP-14: Pfreundschuh M, Poeschel V, Zeynalova S, Hänel M, Held G, Schmitz N, Viardot A, Dreyling MH, Hallek M, Mueller C, Wiesen MH, Witzens-Harig M, Truemper L, Keller U, Rixecker T, Zwick C, Murawski N. Optimization of rituximab for the treatment of diffuse large B-cell lymphoma (II): extended rituximab exposure time in the SMARTE-R-CHOP-14 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group. J Clin Oncol. 2014 Dec 20;32(36):4127-33. Epub 2014 Nov 17. Erratum in: J Clin Oncol. 2015 Jun 10;33(17):1991. link to original article contains verified protocol PubMed
LYSA LNH09-7B: Peyrade F, Bologna S, Delwail V, Emile JF, Pascal L, Fermé C, Schiano JM, Coiffier B, Corront B, Farhat H, Fruchart C, Ghesquieres H, Macro M, Tilly H, Choufi B, Delarue R, Fitoussi O, Gabarre J, Haioun C, Jardin F. Combination of ofatumumab and reduced-dose CHOP for diffuse large B-cell lymphomas in patients aged 80 years or older: an open-label, multicentre, single-arm, phase 2 trial from the LYSA group. Lancet Haematol. 2017 Jan;4(1):e46-e55. link to original article contains protocol PubMed

Untreated, randomized data

ACVBP-R

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ACVBP-R: Adriamycin (Doxorubicin), Cyclophosphamide, Vindesine, Bleomycin, Prednisone, Rituximab
R-ACVBP: Rituximab, Adriamycin (Doxorubicin), Cyclophosphamide, Vindesine, Bleomycin, Prednisone

Regimen

Study	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Récher et al. 2011 (LNH03-2B)	Phase III (E-esc)	R-CHOP	Superior OS	Increased toxicity
Ketterer et al. 2013 (LNH03-1B)	Phase III (E-esc)	ACVBP	Seems to have superior PFS	Similar toxicity

Chemotherapy

Doxorubicin (Adriamycin) 75 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 1200 mg/m² IV once on day 1
Vindesine (Eldisine) 2 mg/m² IV once per day on days 1 & 5
Bleomycin (Blenoxane) 10 units IV once per day on days 1 & 5
Prednisone (Sterapred) 60 mg/m² PO once per day on days 1 to 5
Rituximab (Rituxan) 375 mg/m² IV once on day 1

CNS prophylaxis

Methotrexate (MTX) 15 mg IT on day 1

Supportive medications

Filgrastim (Neupogen) 300 mcg (for patients less than 75 kg) or 480 mcg (for patients greater than or equal to 75 kg) SC once per day on days 6 to 13

14-day cycle for 4 cycles

Subsequent treatment

Methotrexate consolidation, in 4 weeks

References

LNH03-2B: Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, Thiéblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquières H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011 Nov 26;378(9806):1858-67. link to original article contains verified protocol PubMed
1. Subgroup analysis: Molina TJ, Canioni D, Copie-Bergman C, Recher C, Brière J, Haioun C, Berger F, Fermé C, Copin MC, Casasnovas O, Thieblemont C, Petrella T, Leroy K, Salles G, Fabiani B, Morschauser F, Mounier N, Coiffier B, Jardin F, Gaulard P, Jais JP, Tilly H. Young patients with non-germinal center B-cell-like diffuse large B-cell lymphoma benefit from intensified chemotherapy with ACVBP plus rituximab compared with CHOP plus rituximab: analysis of data from the Groupe d'Etudes des Lymphomes de l'Adulte/lymphoma study association phase III trial LNH 03-2B. J Clin Oncol. 2014 Dec 10;32(35):3996-4003. Epub 2014 Nov 10. link to original article PubMed
LNH03-1B: Ketterer N, Coiffier B, Thieblemont C, Fermé C, Brière J, Casasnovas O, Bologna S, Christian B, Connerotte T, Récher C, Bordessoule D, Fruchart C, Delarue R, Bonnet C, Morschhauser F, Anglaret B, Soussain C, Fabiani B, Tilly H, Haioun C. Phase III study of ACVBP versus ACVBP plus rituximab for patients with localized low-risk diffuse large B-cell lymphoma (LNH03-1B). Ann Oncol. 2013 Apr;24(4):1032-7. Epub 2012 Dec 12. link to original article PubMed

DA-R-EPOCH

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DA-R-EPOCH: Dose Adjusted Rituximab, Etoposide, Prednisone, Oncovin (Vincristine), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin)
DA-EPOCH-R

Regimen

Study	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
García-Suárez et al. 2007	Phase II
Wilson et al. 2008	Phase II
Wilson et al. 2011 (CALGB 50103)	Phase II
Purroy et al. 2014	Phase II
Bartlett et al. 2019 (CALGB 50303)	Phase III (E-esc)	R-CHOP	Did not meet primary endpoint of EFS	Increased toxicity

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once per cycle or day 1 before the start of EPOCH (depending on reference)
Etoposide (Vepesid) 50 mg/m²/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 200 mg/m²)
Prednisone (Sterapred) 60 mg/m² PO twice per day on days 1 to 5
Vincristine (Oncovin) 0.4 mg/m²/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg/m²)
Cyclophosphamide (Cytoxan) 750 mg/m² IV over 15 minutes once on day 5
Doxorubicin (Adriamycin) 10 mg/m²/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m²)

Supportive medications

Growth factor support with one of the following:
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 6 and continuing until ANC greater than 5000/uL past nadir
- Pegfilgrastim (Neulasta) 6 mg SC once on day 6 (option per Purroy et al. 2014)
PCP prophylaxis with any one of the following:
- Trimethoprim-Sulfamethoxazole (Bactrim DS) 160/800 mg PO twice per day 3 days per week
  - Alternative used only in García-Suárez et al. 2007: cotrimoxazole 480 mg PO twice per day 3 days per week
- Atovaquone (Mepron) 1500 mg PO once per day
- Pentamidine (Nebupent) 300 mg nebulized every 28 days
Only in García-Suárez et al. 2007: Darbepoetin alfa (Aranesp) 2.25 mcg/kg SC when hemoglobin concentration was less than or equal to 10 g/dL.

21-day cycle for 6 to 8 cycles

Dose modifications

Start cycle 1 as described above.
Obtain CBCs twice per week for nadir measurements.
If nadir ANC greater than 500/uL, increase etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
If nadir ANC less than 500/uL on 1 or 2 measurements, use same doses as last cycle.
If nadir ANC less than 500/uL on at least 3 measurements, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
And/or if nadir platelet count less than 25 × 10⁹/L on at least 1 measurement, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
Dose adjustments below the cycle 1 starting dose only applies to cyclophosphamide. The lowest etoposide and doxorubicin would be dosed at is the original cycle 1 dose.
Can start new cycle every 21 days if ANC greater than 1000/uL and platelets greater than 100 × 10⁹/L. If counts are below those levels, check daily CBC and continue growth factor support until counts are adequate and next cycle can start.

References

García-Suárez J, Bañas H, Arribas I, De Miguel D, Pascual T, Burgaleta C. Dose-adjusted EPOCH plus rituximab is an effective regimen in patients with poor-prognostic untreated diffuse large B-cell lymphoma: results from a prospective observational study. Br J Haematol. 2007 Jan;136(2):276-85. link to original article contains verified protocol PubMed
Wilson WH, Dunleavy K, Pittaluga S, Hegde U, Grant N, Steinberg SM, Raffeld M, Gutierrez M, Chabner BA, Staudt L, Jaffe ES, Janik JE. Phase II study of dose-adjusted EPOCH and rituximab in untreated diffuse large B-cell lymphoma with analysis of germinal center and post-germinal center biomarkers. J Clin Oncol. 2008 Jun 1;26(16):2717-24. link to original article link to PMC article PubMed
CALGB 50103: Wilson WH, Jung SH, Porcu P, Hurd D, Johnson J, Martin SE, Czuczman M, Lai R, Said J, Chadburn A, Jones D, Dunleavy K, Canellos G, Zelenetz AD, Cheson BD, Hsi ED; Cancer Leukemia Group B. A Cancer and Leukemia Group B multi-center study of DA-EPOCH-rituximab in untreated diffuse large B-cell lymphoma with analysis of outcome by molecular subtype. Haematologica. 2012 May;97(5):758-65. Epub 2011 Dec 1. link to original article link to PMC article PubMed
Purroy N, Bergua J, Gallur L, Prieto J, Lopez LA, Sancho JM, García-Marco JA, Castellví J, Montes-Moreno S, Batlle A, de Villambrosia SG, Carnicero F, Ferrando-Lamana L, Piris MA, Lopez A. Long-term follow-up of dose-adjusted EPOCH plus rituximab (DA-EPOCH-R) in untreated patients with poor prognosis large B-cell lymphoma: a phase II study conducted by the Spanish PETHEMA group. Br J Haematol. 2015 Apr;169(2):188-98. Epub 2014 Dec 18. link to original article contains protocol PubMed
Retrospective: Howlett C, Snedecor SJ, Landsburg DJ, Svoboda J, Chong EA, Schuster SJ, Nasta SD, Feldman T, Rago A, Walsh KM, Weber S, Goy A, Mato A. Front-line, dose-escalated immunochemotherapy is associated with a significant progression-free survival advantage in patients with double-hit lymphomas: a systematic review and meta-analysis. Br J Haematol. 2015 Aug;170(4):504-14. Epub 2015 Apr 24. link to original article PubMed
CALGB 50303: Bartlett NL, Wilson WH, Jung SH, Hsi ED, Maurer MJ, Pederson LD, Polley MC, Pitcher BN, Cheson BD, Kahl BS, Friedberg JW, Staudt LM, Wagner-Johnston ND, Blum KA, Abramson JS, Reddy NM, Winter JN, Chang JE, Gopal AK, Chadburn A, Mathew S, Fisher RI, Richards KL, Schöder H, Zelenetz AD, Leonard JP. Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303. J Clin Oncol. 2019 Jul 20;37(21):1790-1799. Epub 2019 Apr 2. link to original article link to PMC article PubMed

R-CHOEP-14

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R-CHOEP-14: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Etoposide, Prednisone, 14-day cycles

Regimen variant #1, flat-dose vincristine

Study	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Adde et al. 2006	Phase II
Schmitz et al. 2012 (DSHNHL 2002-1)	Phase III (C)	R-MegaCHOEP	Did not meet primary endpoint of EFS	Decreased toxicity

Note: to our knowledge, this regimen was not tested as an experimental arm in a RCT prior to becoming a standard comparator arm.

Chemotherapy

Rituximab (Rituxan) as follows:
- Cycles 1 to 4, 6, 8: 375 mg/m² IV once on day 0
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 2 mg IV once on day 1
Etoposide (Vepesid) 100 mg/m² IV once per day on days 1 to 3
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

14-day cycle for 8 cycles

Subsequent treatment

"Mandatory" for patients with bulky disease (any mass greater than 7.5cm in diameter, or extranodal involvement): RT x 36 Gy

Regimen variant #2, capped vincristine, with CNS prophylaxis

Study	Evidence
Holte et al. 2012 (NLG LBC-04)	Phase II

Note: Consolidative radiotherapy "given at the discretion of the individual centers (36 to 45 Gy). Indications for giving radiotherapy after the completion of chemotherapy included bulky disease (greater than or equal to 10 cm) at diagnosis, localized PET-positive residual lesions, and residual disease, not eligible for biopsy at a localized site, and potentially curable by radiotherapy."

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Etoposide (Vepesid) 100 mg/m² IV once per day on days 1 to 3
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

Supportive medications

ONE of the following:
- Filgrastim (Neupogen) 5 mcg/kg SC once per day from day 4
- Pegfilgrastim (Neulasta) 6 mg SC once on day 4

14-day cycle for 8 cycles

Subsequent treatment

CNS prophylaxis: HiDAC, then HD-MTX

References

Adde M, Enblad G, Hagberg H, Sundström C, Laurell A. Outcome for young high-risk aggressive B-cell lymphoma patients treated with CHOEP-14 and rituximab (R-CHOEP-14). Med Oncol. 2006;23(2):283-93. link to original article PubMed
DSHNHL 2002-1: Schmitz N, Nickelsen M, Ziepert M, Haenel M, Borchmann P, Schmidt C, Viardot A, Bentz M, Peter N, Ehninger G, Doelken G, Ruebe C, Truemper L, Rosenwald A, Pfreundschuh M, Loeffler M, Glass B; for the German High-Grade Lymphoma Study Group (DSHNHL). Conventional chemotherapy (CHOEP-14) with rituximab or high-dose chemotherapy (MegaCHOEP) with rituximab for young, high-risk patients with aggressive B-cell lymphoma: an open-label, randomised, phase 3 trial (DSHNHL 2002-1). Lancet Oncol. 2012 Dec;13(12):1250-1259. Epub 2012 Nov 16. link to original article PubMed
NLG LBC-04: Holte H, Leppä S, Björkholm M, Fluge O, Jyrkkiö S, Delabie J, Sundström C, Karjalainen-Lindsberg ML, Erlanson M, Kolstad A, Fosså A, Ostenstad B, Löfvenberg E, Nordström M, Janes R, Pedersen LM, Anderson H, Jerkeman M, Eriksson M. Dose-densified chemoimmunotherapy followed by systemic central nervous system prophylaxis for younger high-risk diffuse large B-cell/follicular grade 3 lymphoma patients: results of a phase II Nordic Lymphoma Group study. Ann Oncol. 2013 May;24(5):1385-92. Epub 2012 Dec 17. link to original article contains verified protocol PubMed

R-CHOP

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R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
R-CHOP-21: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone given every 21 days
CHOP-R: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone, Rituximab
RCHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
CHOPR: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone, Rituximab

Example orders

Example orders for R-CHOP in lymphoma

Note: most of the variation between regimen variants is in the dose of prednisone.

Regimen variant #1, prednisone 40 mg/m²

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Coiffier et al. 2002 (LNH 98-5)	1998-2000	Phase III (E-RT-esc)	CHOP	Superior OS
Delarue et al. 2013 (LNH03-6B)		Phase III (C)	R-CHOP-14	Did not meet primary endpoint of EFS

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 5

Supportive medications

Filgrastim (Neupogen) used for later cycles if patients developed grade 4 neutropenia or febrile neutropenia

21-day cycle for 8 cycles

CNS prophylaxis

As described in Delarue et al. 2013 (LNH03-6B):

Methotrexate (MTX) 15 mg IT once on day 1

21-day cycle for 4 cycles

Regimen variant #2, prednisone 60 mg/m²

Study	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Récher et al. 2011 (LNH03-2B)	Phase III (C)	ACVBP-R	Inferior OS	Decreased toxicity
Li et al. 2018 (CSWOG0001)	Phase III (C)	R-CHOP-14	Did not meet primary endpoint of DFS	Similar toxicities

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) 60 mg/m² PO once per day on days 1 to 5

21-day cycle for 8 cycles

Regimen variant #3, prednisone 100 mg, capped vincristine, 4 cycles

Study	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Poeschel et al. 2019 (FLYER)	Phase III (E-de-esc)	R-CHOP x 6	Non-inferior PFS36	Less toxic

Note: Patients in FLYER were 18 to 60 and had no risk factors according to age-adjusted IPI.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) as follows:
- Cycles 1 to 4: 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) as follows:
- Cycles 1 to 4: 50 mg/m² IV once on day 1
Vincristine (Oncovin) as follows:
- Cycles 1 to 4: 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) as follows:
- Cycles 1 to 4: 100 mg IV or PO once per day on days 1 to 5

21-day cycle for 6 cycles

Regimen variant #4, prednisone 100 mg, capped vincristine, 6 cycles

Study	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Vose et al. 2001	Phase II
Merli et al. 2012 (ANZINTER3)	Phase III (C)	R-miniCEOP	Did not meet primary endpoint of EFS
Herbrecht et al. 2013 (PIX203)	Phase III (C)	CPOP-R	Inconclusive whether non-inferior CR/CRu rate (*)
Oki et al. 2013 (MDACC 2005-0054)	Randomized Phase II (C)	R-Hyper-CVAD/R-MA	Seems to have inferior CRR
Seymour et al. 2014 (MAIN)	Phase III (C)	RA-CHOP-21	Did not meet secondary endpoint of PFS	Better cardiac safety
Vitolo et al. 2017 (GOYA)	Phase III (C)	G-CHOP	Did not meet primary endpoint of PFS
Leonard et al. 2017 (C05013)	Randomized Phase II (C)	VR-CHOP	Did not meet primary endpoint of PFS
Hara et al. 2018	Phase III (C)	R-THP-CHOP	Non-inferior CR rate
Younes et al. 2019 (PHOENIX)	Phase III (C)	IR-CHOP	Did not meet primary endpoint of EFS
Poeschel et al. 2019 (FLYER)	Phase III (C)	R-CHOP x 4	Non-inferior PFS36	More toxic

Note: patients in Vose et al. 2001 received rituximab 2 days before CHOP, i.e., all CHOP days are moved forward by 2 days. Patients in GOYA received 8 doses of rituximab, regardless of the number of chemotherapy cycles given. While the primary endpoing in PIX203 was inconclusive (non-inferiority by CR/CRu rate), this arm seemed to have superior OS. Hara et al. 2018 does not have dosing information available in the abstract. Patients in FLYER were 18 to 60 and had no risk factors according to age-adjusted IPI.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) 100 mg IV or PO once per day on days 1 to 5

Supportive medications

Varies per protocol
Prophylactic G-CSF used for persisting grade 4 neutropenia or febrile neutropenia.
Cotrimoxazole (dose/schedule not specified) prophylaxis.
Erythropoietin use was allowed for hemoglobin less than 11 g/dL.

21-day cycle for 6 to 8 cycles (see note)

Subsequent treatment

Some protocols: Radiation therapy was scheduled for sites of previous bulky disease or partially responding sites

Regimen variant #5, prednisone 100 mg, flat-dose vincristine

Study	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Pfreundschuh et al. 2006 (NCIC CTG LY.9)	Phase III (E-RT-esc)	1. CHOP 2. CHOEP-21 3. MACOP-B 4. PMitCEBO	Superior EFS	Similar toxicity

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 2 mg IV once on day 1
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

Supportive medications

G-CSF with one of the following:
- Filgrastim (Neupogen) used at physician discretion for neutropenia
- Lenograstim (Granocyte) used at physician discretion for neutropenia

21-day cycle for 6 cycles

Subsequent treatment

Radiation therapy 30 to 40 Gy given to sites of primary bulky disease; 30 to 40 Gy to primary extranodal disease at physician discretion

Regimen variant #6, prednisone 100 mg/m²

Study	Evidence	Comparator	Comparative Efficacy
Offner et al. 2015 (LYM-2034)	Randomized Phase II (C)	VR-CAP	Did not meet primary endpoint of CR rate

This regimen was used for non-germinal center B-cell (non-GCB) DLBCL.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) 100 mg/m² PO once per day on days 1 to 5

21-day cycle for 6 cycles

Regimen variant #7, rituximab lead-in

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Habermann et al. 2006 (ECOG E4494/CALGB 9793)	1998-2001	Phase III (E-RT-esc)	CHOP	Seems to have superior FFS

Note: an advantage for maintenance was only seen in the group receiving CHOP upfront, which is no longer standard of care.

Chemotherapy

Rituximab (Rituxan) as follows:
- Cycle 1: 375 mg/m² IV once per day on days -7 & -3
- Cycle 2 onwards: 375 mg/m² IV once on day -2
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) 100 mg/m² PO once per day on days 1 to 5

Supportive medications

Recommended: Filgrastim (Neupogen) "according to guidelines"

21-day cycle for 6 to 8 cycles

Subsequent treatment

Rituximab maintenance versus observation

Regimen variant #8, short-course for early stage DLBCL

Study	Evidence
Persky et al. 2008 (SWOG S0014)	Phase II
Yoon et al. 2017 (CISL 12-09)	Phase II

Note: CISL 12-09 does not have dosing details.

Preceding treatment

CISL 12-09: Surgical resection

Chemotherapy

Rituximab (Rituxan) as follows:
- Prephase: 375 mg/m² IV once on day -7
- Cycles 1 to 3: 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

21-day cycle for 3 cycles

Subsequent treatment

SWOG S0014: IFRT to begin 3 weeks after last cycle of R-CHOP

Regimen variant #9, primary testicular DLBCL

Study	Evidence
Vitolo et al. 2011 (IELSG-10)	Phase II

This regimen is for primary testicular lymphoma, and is a component of a sequential treatment protocol.

Preceding treatment

Diagnostic orchiectomy prior to starting chemotherapy

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 0 or 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

21-day cycle for 6 cycles (up to 8 cycles for stage II patients)

CNS prophylaxis

Methotrexate (MTX) 12 mg IT once per day on days 1, 8, 15, 22

4-week course

Subsequent treatent

RT

Regimen variant #10, 2 cycles with response adaptation

Study	Evidence
Witzig et al. 2015 (ECOG E3402)	Phase II

This regimen is intended for stage I-II DLBCL based on CT (not PET-CT) imaging.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) 100 mg/m² PO once per day on days 1 to 5

21-day cycle for 2 cycles

Subsequent treatment

CR based on CT scan: R-CHOP x 2 (4 cycles total), then ibritumomab tiuxetan consolidation
CRu or PR based on CT scan: R-CHOP x 4 (6 cycles total), then ibritumomab tiuxetan consolidation

References

Vose JM, Link BK, Grossbard ML, Czuczman M, Grillo-Lopez A, Gilman P, Lowe A, Kunkel LA, Fisher RI. Phase II study of rituximab in combination with CHOP chemotherapy in patients with previously untreated, aggressive non-Hodgkin's lymphoma. J Clin Oncol. 2001 Jan 15;19(2):389-97. link to original article contains verified protocol PubMed
LNH 98-5: Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jan 24;346(4):235-42. link to original article contains verified protocol PubMed
1. Update: Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Fermé C, Christian B, Lepage E, Tilly H, Morschhauser F, Gaulard P, Salles G, Bosly A, Gisselbrecht C, Reyes F, Coiffier B. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2005 Jun 20;23(18):4117-26. link to original article contains protocol PubMed
2. Update: Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S, Lefort S, Marit G, Macro M, Sebban C, Belhadj K, Bordessoule D, Fermé C, Tilly H. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte. Blood. 2010 Sep 23;116(12):2040-5. link to original article contains verified protocol link to PMC article PubMed content property of HemOnc.org
3. Update: Mounier N, Heutte N, Thieblemont C, Briere J, Gaulard P, Feugier P, Ghesquieres H, Van Den Neste E, Robu D, Tilly H, Bouabdallah R, Safar V, Coiffier B; Groupe d'Etude des Lymphomes de l'Adulte (GELA). Ten-year relative survival and causes of death in elderly patients treated with R-CHOP or CHOP in the GELA LNH-985 trial. Clin Lymphoma Myeloma Leuk. 2012 Jun;12(3):151-4. Epub 2012 Feb 1. link to original article PubMed
NCIC CTG LY.9: Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. link to original article contains verified protocol PubMed
1. Update: Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N; MabThera International Trial (MInT) Group. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011 Oct;12(11):1013-22. link to original article contains protocol PubMed
ECOG E4494/CALGB 9793: Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, Dakhil SR, Woda B, Fisher RI, Peterson BA, Horning SJ. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006 Jul 1;24(19):3121-7. Epub 2006 Jun 5. link to original article contains verified protocol PubMed
SWOG S0014: Persky DO, Unger JM, Spier CM, Stea B, LeBlanc M, McCarty MJ, Rimsza LM, Fisher RI, Miller TP; Southwest Oncology Group. Phase II study of rituximab plus three cycles of CHOP and involved-field radiotherapy for patients with limited-stage aggressive B-cell lymphoma: Southwest Oncology Group study 0014. J Clin Oncol. 2008 May 10;26(14):2258-63. Epub 2008 Apr 14. link to original article contains verified protocol PubMed
IELSG-10: Vitolo U, Chiappella A, Ferreri AJ, Martelli M, Baldi I, Balzarotti M, Bottelli C, Conconi A, Gomez H, Lopez-Guillermo A, Martinelli G, Merli F, Novero D, Orsucci L, Pavone V, Ricardi U, Storti S, Gospodarowicz MK, Cavalli F, Sarris AH, Zucca E. First-line treatment for primary testicular diffuse large B-cell lymphoma with rituximab-CHOP, CNS prophylaxis, and contralateral testis irradiation: final results of an international phase II trial. J Clin Oncol. 2011 Jul 10;29(20):2766-72. Epub 2011 Jun 6. link to original article contains verified protocol PubMed
ANZINTER3: Merli F, Luminari S, Rossi G, Mammi C, Marcheselli L, Tucci A, Ilariucci F, Chiappella A, Musso M, Di Rocco A, Stelitano C, Alvarez I, Baldini L, Mazza P, Salvi F, Arcari A, Fragasso A, Gobbi PG, Liberati AM, Federico M. Cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab versus epirubicin, cyclophosphamide, vinblastine, prednisone and rituximab for the initial treatment of elderly "fit" patients with diffuse large B-cell lymphoma: results from the ANZINTER3 trial of the Intergruppo Italiano Linfomi. Leuk Lymphoma. 2012 Apr;53(4):581-8. Epub 2011 Nov 15. link to original article contains verified protocol PubMed
LNH03-2B: Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, Thiéblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquières H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011 Nov 26;378(9806):1858-67. link to original article contains verified protocol PubMed
1. Subgroup analysis: Molina TJ, Canioni D, Copie-Bergman C, Recher C, Brière J, Haioun C, Berger F, Fermé C, Copin MC, Casasnovas O, Thieblemont C, Petrella T, Leroy K, Salles G, Fabiani B, Morschauser F, Mounier N, Coiffier B, Jardin F, Gaulard P, Jais JP, Tilly H. Young patients with non-germinal center B-cell-like diffuse large B-cell lymphoma benefit from intensified chemotherapy with ACVBP plus rituximab compared with CHOP plus rituximab: analysis of data from the Groupe d'Etudes des Lymphomes de l'Adulte/lymphoma study association phase III trial LNH 03-2B. J Clin Oncol. 2014 Dec 10;32(35):3996-4003. Epub 2014 Nov 10. link to original article PubMed
LNH03-6B: Delarue R, Tilly H, Mounier N, Petrella T, Salles G, Thieblemont C, Bologna S, Ghesquières H, Hacini M, Fruchart C, Ysebaert L, Fermé C, Casasnovas O, Van Hoof A, Thyss A, Delmer A, Fitoussi O, Molina TJ, Haioun C, Bosly A. Dose-dense rituximab-CHOP compared with standard rituximab-CHOP in elderly patients with diffuse large B-cell lymphoma (the LNH03-6B study): a randomised phase 3 trial. Lancet Oncol. 2013 May;14(6):525-33. Epub 2013 Apr 9. link to original article contains verified protocol PubMed
PIX203: Herbrecht R, Cernohous P, Engert A, Le Gouill S, Macdonald D, Machida C, Myint H, Saleh A, Singer J, Wilhelm M, van der Jagt R. Comparison of pixantrone-based regimen (CPOP-R) with doxorubicin-based therapy (CHOP-R) for treatment of diffuse large B-cell lymphoma. Ann Oncol. 2013 Oct;24(10):2618-23. Epub 2013 Aug 14. link to original article contains verified protocol in supplement PubMed
MDACC 2005-0054: Oki Y, Westin JR, Vega F, Chuang H, Fowler N, Neelapu S, Hagemeister FB, McLaughlin P, Kwak LW, Romaguera JE, Fanale M, Younes A, Rodriguez MA, Orlowski RZ, Wang M, Ouzounian ST, Samaniego F, Fayad L. Prospective phase II study of rituximab with alternating cycles of hyper-CVAD and high-dose methotrexate with cytarabine for young patients with high-risk diffuse large B-cell lymphoma. Br J Haematol. 2013 Dec;163(5):611-20. Epub 2013 Oct 1. link to original article contains verified protocol link to PMC article contains verified protocol PubMed
SWOG S9704: Stiff PJ, Unger JM, Cook JR, Constine LS, Couban S, Stewart DA, Shea TC, Porcu P, Winter JN, Kahl BS, Miller TP, Tubbs RR, Marcellus D, Friedberg JW, Barton KP, Mills GM, LeBlanc M, Rimsza LM, Forman SJ, Fisher RI. Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. N Engl J Med. 2013 Oct 31;369(18):1681-90. link to original article link to PMC article does not contain protocol PubMed
1. Subgroup analysis: Puvvada SD, Stiff PJ, Leblanc M, Cook JR, Couban S, Leonard JP, Kahl B, Marcellus D, Shea TC, Winter JN, Li H, Rimsza LM, Friedberg JW, Smith SM. Outcomes of MYC-associated lymphomas after R-CHOP with and without consolidative autologous stem cell transplant: subset analysis of randomized trial intergroup SWOG S9704. Br J Haematol. 2016 Sep;174(5):686-91. Epub 2016 Apr 13. link to original article link to PMC article PubMed
MAIN: Seymour JF, Pfreundschuh M, Trnený M, Sehn LH, Catalano J, Csinady E, Moore N, Coiffier B; MAIN Study Investigators. R-CHOP with or without bevacizumab in patients with previously untreated diffuse large B-cell lymphoma: final MAIN study outcomes. Haematologica. 2014 Aug;99(8):1343-9. Epub 2014 Jun 3. link to original article link to PMC article does not contain protocol PubMed
Retrospective: Howlett C, Snedecor SJ, Landsburg DJ, Svoboda J, Chong EA, Schuster SJ, Nasta SD, Feldman T, Rago A, Walsh KM, Weber S, Goy A, Mato A. Front-line, dose-escalated immunochemotherapy is associated with a significant progression-free survival advantage in patients with double-hit lymphomas: a systematic review and meta-analysis. Br J Haematol. 2015 Aug;170(4):504-14. Epub 2015 Apr 24. link to original article PubMed
ECOG E3402: Witzig TE, Hong F, Micallef IN, Gascoyne RD, Dogan A, Wagner H Jr, Kahl BS, Advani RH, Horning SJ. A phase II trial of RCHOP followed by radioimmunotherapy for early stage (stages I/II) diffuse large B-cell non-Hodgkin lymphoma: ECOG3402. Br J Haematol. 2015 Sep;170(5):679-86. Epub 2015 May 14. link to original article contains verified protocol link to PMC article PubMed
LYM-2034: Offner F, Samoilova O, Osmanov E, Eom HS, Topp MS, Raposo J, Pavlov V, Ricci D, Chaturvedi S, Zhu E, van de Velde H, Enny C, Rizo A, Ferhanoglu B. Frontline rituximab, cyclophosphamide, doxorubicin, and prednisone with bortezomib (VR-CAP) or vincristine (R-CHOP) for non-GCB DLBCL. Blood. 2015 Oct 15;126(16):1893-901. Epub 2015 Jul 31. link to original article contains verified protocol link to PMC article PubMed
CISL 12-09: Yoon DH, Sohn BS, Oh SY, Lee WS, Lee SM, Yang DH, Huh J, Suh C. Feasibility of abbreviated cycles of immunochemotherapy for completely resected limited-stage CD20+ diffuse large B-cell lymphoma (CISL 12-09). Oncotarget. 2017 Feb 21;8(8):13367-13374. link to original article link to PMC article does not contain protocol PubMed
MabEase: Lugtenburg P, Avivi I, Berenschot H, Ilhan O, Marolleau JP, Nagler A, Rueda A, Tani M, Turgut M, Osborne S, Smith R, Pfreundschuh M. Efficacy and safety of subcutaneous and intravenous rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in first-line diffuse large B-cell lymphoma: the randomized MabEase study. Haematologica. 2017 Nov;102(11):1913-1922. Epub 2017 Sep 21. link to original article contains partial protocol PubMed
GOYA: Vitolo U, Trněný M, Belada D, Burke JM, Carella AM, Chua N, Abrisqueta P, Demeter J, Flinn I, Hong X, Kim WS, Pinto A, Shi YK, Tatsumi Y, Oestergaard MZ, Wenger M, Fingerle-Rowson G, Catalani O, Nielsen T, Martelli M, Sehn LH. Obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in previously untreated diffuse large B-cell lymphoma. J Clin Oncol. 2017 Nov 1;35(31):3529-3537. Epub 2017 Aug 10. link to original article contains verified protocol PubMed
C05013: Leonard JP, Kolibaba KS, Reeves JA, Tulpule A, Flinn IW, Kolevska T, Robles R, Flowers CR, Collins R, DiBella NJ, Papish SW, Venugopal P, Horodner A, Tabatabai A, Hajdenberg J, Park J, Neuwirth R, Mulligan G, Suryanarayan K, Esseltine DL, de Vos S. Randomized phase II study of R-CHOP with or without bortezomib in previously untreated patients with non-germinal center B-cell-like diffuse large B-cell lymphoma. J Clin Oncol. 2017 Nov 1;35(31):3538-3546. Epub 2017 Sep 1. link to original article contains verified protocol PubMed
Hara T, Yoshikawa T, Goto H, Sawada M, Yamada T, Fukuno K, Kasahara S, Shibata Y, Matsumoto T, Mabuchi R, Nakamura N, Nakamura H, Ninomiya S, Kitagawa J, Kanemura N, Nannya Y, Katsumura N, Takahashi T, Kito Y, Takami T, Miyazaki T, Takeuchi T, Shimizu M, Tsurumi H. R-THP-COP versus R-CHOP in patients younger than 70 years with untreated diffuse large B cell lymphoma: A randomized, open-label, noninferiority phase 3 trial. Hematol Oncol. 2018 Oct;36(4):638-644. Epub 2018 Jun 8. link to original article PubMed
CSWOG0001: Li X, Huang H, Xu B, Guo H, Lin Y, Ye S, Yi J, Li W, Wu X, Wang W, Zhan H, Xie D, Peng J, Cao Y, Pu X, Guo C, Hong H, Wang Z, Fang X, Zhou Y, Lin S, Liu Q, Lin T. Dose-Dense Rituximab-CHOP versus Standard Rituximab-CHOP in Newly Diagnosed Chinese Patients with Diffuse Large B-Cell Lymphoma: A Randomized, Multicenter, Open-Label Phase 3 Trial. Cancer Res Treat. 2019 Jul;51(3):919-932. Epub 2018 Oct 2. link to original article link to PMC article contains verified protocol PubMed
PHOENIX: Younes A, Sehn LH, Johnson P, Zinzani PL, Hong X, Zhu J, Patti C, Belada D, Samoilova O, Suh C, Leppä S, Rai S, Turgut M, Jurczak W, Cheung MC, Gurion R, Yeh SP, Lopez-Hernandez A, Dührsen U, Thieblemont C, Chiattone CS, Balasubramanian S, Carey J, Liu G, Shreeve SM, Sun S, Zhuang SH, Vermeulen J, Staudt LM, Wilson W; PHOENIX investigators. Randomized phase III trial of ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in non-germinal center B-cell diffuse large B-cell lymphoma. J Clin Oncol. 2019 May 20;37(15):1285-1295. Epub 2019 Mar 22. link to original article link to PMC article PubMed
CALGB 50303: Bartlett NL, Wilson WH, Jung SH, Hsi ED, Maurer MJ, Pederson LD, Polley MC, Pitcher BN, Cheson BD, Kahl BS, Friedberg JW, Staudt LM, Wagner-Johnston ND, Blum KA, Abramson JS, Reddy NM, Winter JN, Chang JE, Gopal AK, Chadburn A, Mathew S, Fisher RI, Richards KL, Schöder H, Zelenetz AD, Leonard JP. Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303. J Clin Oncol. 2019 Jul 20;37(21):1790-1799. Epub 2019 Apr 2. link to original article link to PMC article PubMed
FLYER: Poeschel V, Held G, Ziepert M, Witzens-Harig M, Holte H, Thurner L, Borchmann P, Viardot A, Soekler M, Keller U, Schmidt C, Truemper L, Mahlberg R, Marks R, Hoeffkes HG, Metzner B, Dierlamm J, Frickhofen N, Haenel M, Neubauer A, Kneba M, Merli F, Tucci A, de Nully Brown P, Federico M, Lengfelder E, di Rocco A, Trappe R, Rosenwald A, Berdel C, Maisenhoelder M, Shpilberg O, Amam J, Christofyllakis K, Hartmann F, Murawski N, Stilgenbauer S, Nickelsen M, Wulf G, Glass B, Schmitz N, Altmann B, Loeffler M, Pfreundschuh M; FLYER Trial Investigators; German Lymphoma Alliance. Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER): a randomised, phase 3, non-inferiority trial. Lancet. 2019 Dec 21;394(10216):2271-2281. link to original article contains protocol PubMed

R-CHOP (Prednisolone)

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R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisolone

Example orders

Example orders for R-CHOP in lymphoma

Regimen variant #1, prednisolone 40 mg/m²

Study	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Cunningham et al. 2013 (UK NCRI R-CHOP14v21)	Phase III (C)	R-CHOP-14	Did not meet primary endpoint of OS
Fridrik et al. 2016 (AGMT NHL-14)	Phase III (C)	R-COMP	Did not meet secondary efficacy endpoints	Did not meet primary endpoint of reduced cardiotoxicity

Note: Cunningham et al. 2013 states that the regimen is based on LNH 98-5, but notably it uses prednisolone instead of prednisone. AGMT NHL-14 states that R-CHOP was "given in standard doses" per LNH 98-5, but this regimen uses prednisone, whereas the title and text of Fridrik et al. 2016 implies that prednisolone was used. The authors have confirmed that prednisolone was used, due to prednisone not being available in Austria.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisolone (Millipred) 40 mg/m² PO once per day on days 1 to 5

CNS prophylaxis

Per investigator discretion, but Cunningham et al. 2013 recommended that patients who had involvement of the "bone marrow, peripheral blood, nasal or paranasal sinuses, orbit, and testis" (they probably intended to say "or testis") receive:

Methotrexate (MTX) 12.5 mg IT "for the first three cycles of treatment, administered as per local guidelines." No other details given.

Supportive medications

Described in Cunningham et al. 2013
Lenograstim (Granocyte) (dose/route not specified) given on days 4 to 12 at physician discretion
Allopurinol (Zyloprim) 300 mg PO once per day during cycle 1
Co-trimoxazole 80/400 mg PO twice per day on 3 days per week, taken throughout therapy, ending 2 weeks after chemotherapy is completed

21-day cycle for 8 cycles

Regimen variant #2, prednisolone 100 mg, capped vincristine, 4 cycles

Study	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Poeschel et al. 2019 (FLYER)	Phase III (E-de-esc)	R-CHOP x 6	Non-inferior PFS36	Less toxic

Note: Patients in FLYER were 18 to 60 and had no risk factors according to age-adjusted IPI.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) as follows:
- Cycles 1 to 4: 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) as follows:
- Cycles 1 to 4: 50 mg/m² IV once on day 1
Vincristine (Oncovin) as follows:
- Cycles 1 to 4: 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisolone (Millipred) as follows:
- Cycles 1 to 4: 100 mg IV or PO once per day on days 1 to 5

21-day cycle for 6 cycles

Regimen variant #3, prednisolone 100 mg, 6 cycles

Study	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Davies et al. 2019 (REMoDL-B)	Phase III (C)	RB-CHOP	Did not meet primary endpoint of PFS30
Poeschel et al. 2019 (FLYER)	Phase III (C)	R-CHOP x 4	Non-inferior PFS36	More toxic

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisolone (Millipred) 100 mg PO once per day on days 1 to 5

21-day cycle for 6 cycles

Regimen variant #4, prednisolone 100 mg/m²

Study	Evidence	Comparator	Comparative Efficacy
Payandeh et al. 2016	Phase III (C)	R-CHOP-14	Inferior OS

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisolone (Millipred) 100 mg/m² PO once per day on days 1 to 5

21-day cycle for 6 to 8 cycles

References

UK NCRI R-CHOP14v21: Cunningham D, Hawkes EA, Jack A, Qian W, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford JA, McMillan A, Davies J, Turner D, Kruger A, Johnson P, Gambell J, Linch D. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet. 2013 May 25;381(9880):1817-26. Epub 2013 Apr 22. link to original article contains verified protocol PubMed
AGMT NHL-14: Fridrik MA, Jaeger U, Petzer A, Willenbacher W, Keil F, Lang A, Andel J, Burgstaller S, Krieger O, Oberaigner W, Sihorsch K, Greil R. Cardiotoxicity with rituximab, cyclophosphamide, non-pegylated liposomal doxorubicin, vincristine and prednisolone compared to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone in frontline treatment of patients with diffuse large B-cell lymphoma: A randomised phase-III study from the Austrian Cancer Drug Therapy Working Group [Arbeitsgemeinschaft Medikamentöse Tumortherapie AGMT](NHL-14). Eur J Cancer. 2016 May;58:112-21. Epub 2016 Mar 15. link to original article does not contain protocol PubMed
Payandeh M, Najafi S, Shojaiyan FZ, Sadeghi M. Phase III of study of R-CHOP-21 vs R-CHOP-14 for untreated stage III and IV B-cell non-Hodgkin's lymphoma: a report from Iran. Asian Pac J Cancer Prev. 2016;17(3):1513-7. link to original article contains verified protocol PubMed
REMoDL-B: Davies A, Cummin TE, Barrans S, Maishman T, Mamot C, Novak U, Caddy J, Stanton L, Kazmi-Stokes S, McMillan A, Fields P, Pocock C, Collins GP, Stephens R, Cucco F, Clipson A, Sha C, Tooze R, Care MA, Griffiths G, Du MQ, Westhead DR, Burton C, Johnson PWM. Gene-expression profiling of bortezomib added to standard chemoimmunotherapy for diffuse large B-cell lymphoma (REMoDL-B): an open-label, randomised, phase 3 trial. Lancet Oncol. 2019 May;20(5):649-662. Epub 2019 Apr 1. link to original article link to PMC article PubMed
FLYER: Poeschel V, Held G, Ziepert M, Witzens-Harig M, Holte H, Thurner L, Borchmann P, Viardot A, Soekler M, Keller U, Schmidt C, Truemper L, Mahlberg R, Marks R, Hoeffkes HG, Metzner B, Dierlamm J, Frickhofen N, Haenel M, Neubauer A, Kneba M, Merli F, Tucci A, de Nully Brown P, Federico M, Lengfelder E, di Rocco A, Trappe R, Rosenwald A, Berdel C, Maisenhoelder M, Shpilberg O, Amam J, Christofyllakis K, Hartmann F, Murawski N, Stilgenbauer S, Nickelsen M, Wulf G, Glass B, Schmitz N, Altmann B, Loeffler M, Pfreundschuh M; FLYER Trial Investigators; German Lymphoma Alliance. Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER): a randomised, phase 3, non-inferiority trial. Lancet. 2019 Dec 21;394(10216):2271-2281. link to original article contains protocol PubMed

R-CHOP (Rituximab Hycela)

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R-CHOP: Rituximab Hycela, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisolone

Example orders

Example orders for R-CHOP in lymphoma

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Lugtenburg et al. 2017 (MabEase)	2012-NR	Phase III (E-RT-switch-ic)	R-CHOP	Might have superior CR rate

Note: the details for CHOP are not available in the manuscript or supplement; we have reproduced common CHOP dosing, here. For patients achieving CR after cycle 4, the CHOP could be omitted after cycle 6.

Chemotherapy

Rituximab (Rituxan) as follows:
- Cycle 1: 375 mg/m² IV once on day 1
Rituximab and hyaluronidase human (Rituxan Hycela) as follows:
- Cycles 2 to 8: 1400 mg SC once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) 100 mg/m² PO once per day on days 1 to 5

21-day cycle for 6 to 8 cycles

References

MabEase: Lugtenburg P, Avivi I, Berenschot H, Ilhan O, Marolleau JP, Nagler A, Rueda A, Tani M, Turgut M, Osborne S, Smith R, Pfreundschuh M. Efficacy and safety of subcutaneous and intravenous rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in first-line diffuse large B-cell lymphoma: the randomized MabEase study. Haematologica. 2017 Nov;102(11):1913-1922. Epub 2017 Sep 21. link to original article contains partial protocol PubMed

R-CHOP-14

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R-CHOP-14: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone every 14 days

Synopsis

To be completed. Note that most of the variation below is in the steroid dose.

Regimen variant #1, prednisone 40 mg/m², 4 to 6 cycles

Study	Evidence
Lamy et al. 2017 (LYSA/GOELAMS 02-03)	Non-randomized portion of RCT

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 5

14-day cycle for 4 to 6 cycles

Subsequent treatment

Observation versus IFRT x 40 Gy

Regimen variant #2, prednisone 40 mg/m², 8 cycles

Study	Evidence	Comparator	Comparative Efficacy
Delarue et al. 2013 (LNH03-6B)	Phase III (E-esc)	R-CHOP21	Did not meet primary endpoint of EFS

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 5

Supportive medications

ONE of the following, "according to the treating doctor's decision, fulfilling existing guidelines and product labelling at that time."
- Granulocyte colony-stimulating factor
- Pegylated G-CSF

14-day cycle for 8 cycles

CNS prophylaxis

Methotrexate (MTX) 15 mg IT once on day 1

14-day cycle for 4 cycles

Regimen variant #3, prednisone 100 mg, BSA-based vincristine, standard-dose IV rituximab

Study	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Seymour et al. 2014 (MAIN)	Phase III (C)	RA-CHOP-14	Did not meet secondary endpoint of PFS	Better cardiac safety
Cortelazzo et al. 2016	Phase III (C)	R-HDS	Did not meet primary endpoint of EFS36
Chiappella et al. 2017 (DLCL04)	Phase III (C)	1. R-MegaCHOP-14	Not reported
Chiappella et al. 2017 (DLCL04)	Phase III (C)	2. R-CHOP-14, then R-MAD, then BEAM, then auto HSCT 3. R-MegaCHOP-14, then R-MAD, then BEAM, then auto HSCT	Did not meet primary endpoint of FFS24

Note: in MAIN, CHOP-14 was given for 6 cycles and rituximab for 8 cycles. In Cortelazzo et al. 2016, there is no cap on the vincristine dose, and there is also a discrepancy between the prednisone dose in the body of the manuscript and that in the appendix Figure A1; these discrepancies were clarified by the corresponding author in January 2017. In the abstract of DLCL04, there is no cap on vincristine.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

Supportive medications

ONE of the following:
- Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 7 to 11
- Pegfilgrastim (Neulasta)

14-day cycle for 6 to 8 cycles (see note)

Regimen variant #4, prednisone 100 mg, BSA-based vincristine, high-dose IV rituximab

Study	Evidence	Comparator	Comparative Efficacy
Pfreundschuh et al. 2014 (SEXIE-R-CHOP-14)	Randomized Phase II (E-esc)	See below	TBD

Note: two arms were assessed; results are pending from this comparison. These higher doses were for males, only.

Chemotherapy

Rituximab (Rituxan) by ONE of the following schedules:
- Cycles 1 to 8: 500 mg/m² IV once on day 1
- 500 mg/m² IV once per day on days -1, 0, 3, 7, 14, 21, 28, 42
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 2 mg IV once on day 1
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

14-day cycle for 6 cycles

Regimen variant #5, prednisone 100 mg, flat dose vincristine, 2 cycles, with response adaptation

Study	Evidence
Dührsen et al. 2018 (PETAL)	Non-randomized portion of RCT

Preceding treatment

Pre-phase vincristine & prednisone

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 2
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 2
Vincristine (Oncovin) 2 mg IV once on day 2
Prednisone (Sterapred) 100 mg PO once per day on days 2 to 6

14-day cycle for 2 cycles

Subsequent treatment

PET-negative: R-CHOP x 4 (6 cycles total) versus R-CHOP x 4, then rituximab x 2
PET-positive: R-CHOP x 6 (8 cycles total) versus intensive Burkitt lymphoma protocol

Regimen variant #6, prednisone 100 mg, flat dose vincristine, 6 cycles, extended rituximab exposure

Study	Evidence
Pfreundschuh et al. 2014 (SMARTE-R-CHOP-14)	Phase II

Preceding treatment

Pre-phase vincristine & prednisone

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once per day on days -4, 0, 10, 29, 57, 99, 155, 239 (independent of CHOP cycles)
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 2 mg IV once on day 1
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

Supportive medications

ONE of the following starting on day 4, to continue until count recovery:
- Filgrastim (Neupogen)
- Lenograstim (Granocyte)

14-day cycle for 6 cycles

Subsequent treatment

Patients with initial bulky disease ("lymphoma masses or conglomerates with a diameter greater than or equal to 7.5 cm) or extranodal involvement"): RT x 36 Gy

Regimen variant #7, prednisone 100 mg, flat dose vincristine, 6-8 cycles

Study	Evidence	Comparator	Comparative Efficacy
Pfreundschuh et al. 2008 (RICOVER-60)	Phase III (E-esc)	1. CHOP-14 x 6	Superior OS
		2. CHOP-14 x 8	Not reported
		3. R-CHOP-14 x 8	Not reported
Held et al. 2014 (RICOVER-noRTh)	Non-randomized portion of RCT

Preceding treatment

RICOVER-60: Pre-phase vincristine & prednisone

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 2 mg IV once on day 1
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

Supportive medications

ONE of the following starting on day 4, to continue until count recovery:
- Filgrastim (Neupogen)
- Lenograstim (Granocyte)

14-day cycle for 6 to 8 cycles (8 doses of rituximab regardless of total number of cycles)

Subsequent treatment

RICOVER-60: Patients with initial bulky disease ("lymphoma masses or conglomerates with a diameter greater than or equal to 7.5 cm) or extranodal involvement"): RT x 36 Gy
RICOVER-noRTh: RT x 36 Gy versus observation

References

RICOVER-60: Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, Reiser M, Nickenig C, Clemens M, Peter N, Bokemeyer C, Eimermacher H, Ho A, Hoffmann M, Mertelsmann R, Trümper L, Balleisen L, Liersch R, Metzner B, Hartmann F, Glass B, Poeschel V, Schmitz N, Ruebe C, Feller AC, Loeffler M; German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 2008 Feb;9(2):105-16. link to original article contains verified protocol PubMed
Abstract: S. Le Gouill, N. J. Milpied, T. Lamy, V. Delwail, R. Gressin, D. Guyotat, G. L. Damaj, C. Foussard, G. Cartron, H. Maisonneuve, E. Deconinck, F. Dreyfus, E. Gyan, L. Sutton, N. Morineau, M. Alexis, F. Perry, M. Sauvezie. First-line rituximab (R) high-dose therapy (R-HDT) versus R-CHOP14 for young adults with diffuse large B-cell lymphoma: Preliminary results of the GOELAMS 075 prospective multicenter randomized trial. Journal of Clinical Oncology 29, no. 15_suppl (May 2011) 8003-8003. link to abstract
LNH03-6B: Delarue R, Tilly H, Mounier N, Petrella T, Salles G, Thieblemont C, Bologna S, Ghesquières H, Hacini M, Fruchart C, Ysebaert L, Fermé C, Casasnovas O, Van Hoof A, Thyss A, Delmer A, Fitoussi O, Molina TJ, Haioun C, Bosly A. Dose-dense rituximab-CHOP compared with standard rituximab-CHOP in elderly patients with diffuse large B-cell lymphoma (the LNH03-6B study): a randomised phase 3 trial. Lancet Oncol. 2013 May;14(6):525-33. Epub 2013 Apr 9. link to original article contains verified protocol PubMed
RICOVER-noRTh: Held G, Murawski N, Ziepert M, Fleckenstein J, Pöschel V, Zwick C, Bittenbring J, Hänel M, Wilhelm S, Schubert J, Schmitz N, Löffler M, Rübe C, Pfreundschuh M. Role of radiotherapy to bulky disease in elderly patients with aggressive B-cell lymphoma. J Clin Oncol. 2014 Apr 10;32(11):1112-8. Epub 2014 Feb 3. link to original article PubMed
Abstract: Michael Pfreundschuh, Gerhard Held, Samira Zeynalova, Carsten Zwick, Mathias Haenel, Lorenz Truemper, Martin H. Dreyling, Judith Dierlamm, Markus Loeffler, Norbert Schmitz, Niels Murawski, German High-Grad Non-Hodgkin Lymphoma Study Group (DSHNHL). Increased rituximab (R) doses and effect on risk of elderly male patients with aggressive CD20+ B-cell lymphomas: Results from the SEXIE-R-CHOP-14 trial of the DSHNHL. J Clin Oncol 32:5s, 2014 (suppl; abstr 8501) link to original abstract
MAIN: Seymour JF, Pfreundschuh M, Trnený M, Sehn LH, Catalano J, Csinady E, Moore N, Coiffier B; MAIN Study Investigators. R-CHOP with or without bevacizumab in patients with previously untreated diffuse large B-cell lymphoma: final MAIN study outcomes. Haematologica. 2014 Aug;99(8):1343-9. Epub 2014 Jun 3. link to original article link to PMC article does not contain protocol PubMed
SMARTE-R-CHOP-14: Pfreundschuh M, Poeschel V, Zeynalova S, Hänel M, Held G, Schmitz N, Viardot A, Dreyling MH, Hallek M, Mueller C, Wiesen MH, Witzens-Harig M, Truemper L, Keller U, Rixecker T, Zwick C, Murawski N. Optimization of rituximab for the treatment of diffuse large B-cell lymphoma (II): extended rituximab exposure time in the SMARTE-R-CHOP-14 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group. J Clin Oncol. 2014 Dec 20;32(36):4127-33. Epub 2014 Nov 17. Erratum in: J Clin Oncol. 2015 Jun 10;33(17):1991. link to original article contains verified protocol PubMed
Cortelazzo S, Tarella C, Gianni AM, Ladetto M, Barbui AM, Rossi A, Gritti G, Corradini P, Di Nicola M, Patti C, Mulé A, Zanni M, Zoli V, Billio A, Piccin A, Negri G, Castellino C, Di Raimondo F, Ferreri AJ, Benedetti F, La Nasa G, Gini G, Trentin L, Frezzato M, Flenghi L, Falorio S, Chilosi M, Bruna R, Tabanelli V, Pileri S, Masciulli A, Delaini F, Boschini C, Rambaldi A. Randomized trial comparing R-CHOP versus high-dose sequential chemotherapy in high-risk patients with diffuse large B-cell lymphomas. J Clin Oncol. 2016 Nov 20;34(33):4015-4022. Epub 2016 Oct 31. link to original article contains verified protocol PubMed
DLCL04: Chiappella A, Martelli M, Angelucci E, Brusamolino E, Evangelista A, Carella AM, Stelitano C, Rossi G, Balzarotti M, Merli F, Gaidano G, Pavone V, Rigacci L, Zaja F, D'Arco A, Cascavilla N, Russo E, Castellino A, Gotti M, Congiu AG, Cabras MG, Tucci A, Agostinelli C, Ciccone G, Pileri SA, Vitolo U. Rituximab-dose-dense chemotherapy with or without high-dose chemotherapy plus autologous stem-cell transplantation in high-risk diffuse large B-cell lymphoma (DLCL04): final results of a multicentre, open-label, randomised, controlled, phase 3 study. Lancet Oncol. 2017 Aug;18(8):1076-1088. Epub 2017 Jun 28. link to original article contains protocol PubMed
MabEase: Lugtenburg P, Avivi I, Berenschot H, Ilhan O, Marolleau JP, Nagler A, Rueda A, Tani M, Turgut M, Osborne S, Smith R, Pfreundschuh M. Efficacy and safety of subcutaneous and intravenous rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in first-line diffuse large B-cell lymphoma: the randomized MabEase study. Haematologica. 2017 Nov;102(11):1913-1922. Epub 2017 Sep 21. link to original article contains partial protocol PubMed
Lamy T, Damaj G, Soubeyran P, Gyan E, Cartron G, Bouabdallah K, Gressin R, Cornillon J, Banos A, Le Du K, Benchalal M, Moles MP, Le Gouill S, Fleury J, Godmer P, Maisonneuve H, Deconinck E, Houot R, Laribi K, Marolleau JP, Tournilhac O, Branger B, Devillers A, Vuillez JP, Fest T, Colombat P, Costes V, Szablewski V, Béné MC, Delwail V; LYSA Group. R-CHOP 14 with or without radiotherapy in nonbulky limited-stage diffuse large B-cell lymphoma. Blood. 2018 Jan 11;131(2):174-181. Epub 2017 Oct 23. link to original article contains verified protocol PubMed
PETAL: Dührsen U, Müller S, Hertenstein B, Thomssen H, Kotzerke J, Mesters R, Berdel WE, Franzius C, Kroschinsky F, Weckesser M, Kofahl-Krause D, Bengel FM, Dürig J, Matschke J, Schmitz C, Pöppel T, Ose C, Brinkmann M, La Rosée P, Freesmeyer M, Hertel A, Höffkes HG, Behringer D, Prange-Krex G, Wilop S, Krohn T, Holzinger J, Griesshammer M, Giagounidis A, Raghavachar A, Maschmeyer G, Brink I, Bernhard H, Haberkorn U, Gaska T, Kurch L, van Assema DME, Klapper W, Hoelzer D, Geworski L, Jöckel KH, Scherag A, Bockisch A, Rekowski J, Hüttmann A; PETAL Trial Investigators. Positron emission tomography-guided therapy of aggressive non-Hodgkin lymphomas (PETAL): a multicenter, randomized phase III trial. J Clin Oncol. 2018 Jul 10;36(20):2024-2034. Epub 2018 May 11. link to original article contains verified protocol in supplement PubMed

R-CHOP-14 (Prednisolone)

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R-CHOP-14: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisolone every 14 days

Regimen

Study	Evidence	Comparator	Comparative Efficacy
Cunningham et al. 2013 (UK NCRI R-CHOP14v21)	Phase III (E-esc)	R-CHOP-21	Did not meet primary endpoint of OS

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) as follows:
- Cycles 1 to 6: 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) as follows:
- Cycles 1 to 6: 50 mg/m² IV once on day 1
Vincristine (Oncovin) as follows:
- Cycles 1 to 6: 2 mg IV once on day 1
Prednisolone (Millipred) as follows:
- Cycles 1 to 6: 100 mg PO once per day on days 1 to 5

CNS prophylaxis

Per investigator discretion, but Cunningham et al. 2013 recommended that patients who had involvement of the "bone marrow, peripheral blood, nasal or paranasal sinuses, orbit, and testis" (they probably intended to say "or testis") receive:

Methotrexate (MTX) 12.5 mg IT "for the first three cycles of treatment, administered as per local guidelines." No other details given.

Supportive medications

Lenograstim (Granocyte) (dose/route not specified) given on days 4 to 12
Allopurinol (Zyloprim) 300 mg PO once per day during cycle 1
Co-trimoxazole 480 mg (route not specified) twice per day on 3 days per week, taken throughout therapy, ending 2 weeks after treatment is completed

14-day cycle for 8 cycles

References

UK NCRI R-CHOP14v21: Cunningham D, Hawkes EA, Jack A, Qian W, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford JA, McMillan A, Davies J, Turner D, Kruger A, Johnson P, Gambell J, Linch D. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet. 2013 May 25;381(9880):1817-26. Epub 2013 Apr 22. link to original article contains verified protocol PubMed

R-CHOP-14 (Rituximab Hycela)

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R-CHOP-14: Rituximab hyaluronidaase, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone every 14 days

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Lugtenburg et al. 2017 (MabEase)	2012-NR	Phase III (E-RT-switch-ic)	R-CHOP-14	Might have superior CR rate

Note: the details for CHOP-14 are not available in the manuscript or supplement; we have reproduced common CHOP-14 dosing, here. For patients achieving CR after cycle 4, the CHOP-14 could be omitted after cycle 6.

Chemotherapy

Rituximab (Rituxan) as follows:
- Cycle 1: 375 mg/m² IV once on day 1
Rituximab and hyaluronidase human (Rituxan Hycela) as follows:
- Cycles 2 to 8: 1400 mg SC once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

Supportive medications

ONE of the following:
- Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 7 to 11
- Pegfilgrastim (Neulasta)

14-day cycle for 6 to 8 cycles

References

MabEase: Lugtenburg P, Avivi I, Berenschot H, Ilhan O, Marolleau JP, Nagler A, Rueda A, Tani M, Turgut M, Osborne S, Smith R, Pfreundschuh M. Efficacy and safety of subcutaneous and intravenous rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in first-line diffuse large B-cell lymphoma: the randomized MabEase study. Haematologica. 2017 Nov;102(11):1913-1922. Epub 2017 Sep 21. link to original article contains partial protocol PubMed

R-Hyper-CVAD/R-MA

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R-Hyper-CVAD/R-MA: Rituximab, Hyperfractionated Cyclophosphamide, Vincristine, Adriamycin (Doxorubicin), Dexamethasone alternating with Rituximab, Methotrexate, Ara-C (Cytarabine)

Protocol

Study	Evidence	Comparator	Comparative Efficacy
Oki et al. 2013 (MDACC 2005-0054)	Randomized Phase II (E-esc)	R-CHOP	Seems to have increased CRR

Intended for high-risk DLBCL (IPI greater than or equal to 3). The authors report "excellent outcome" in patients less than or equal to 45 years old, however patients greater than 45 years old had "unacceptable mortality."

Chemotherapy, part A (cycles 1, 3, 5)

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 300 mg/m² IV every 12 hours on days 1 to 3 (total dose per cycle: 1800 mg/m²)
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once per day on days 5 & 12
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 5
Dexamethasone (Decadron) 40 mg IV or PO once per day on days 2 to 5

Supportive medications

Mesna (Mesnex) 600 mg/m²/day IV continuous infusion over 72 hours, started on day 1 (total dose per cycle: 1800 mg/m²)
Filgrastim (Neupogen) or Pegfilgrastim (Neulasta) starting 24 to 48 hours after completion of chemotherapy
Ciprofloxacin (Cipro) 500 mg PO twice per day for 10 days after chemotherapy
Fluconazole (Diflucan) 100 mg PO once per day for 10 days after chemotherapy
Valacyclovir (Valtrex) 500 mg PO once per day for 10 days after chemotherapy

Dose modifications

Vincristine (Oncovin) reduced once by 50% for NCI common toxicity criteria Grade 2+ peripheral neuropathy, omitted if Grade 2+ peripheral neuropathy persists
Doxorubicin (Adriamycin) and Cyclophosphamide (Cytoxan) reduced by 20% in subsequent A cycles if neutropenic fever occurs, grade 3/4 non-hematological toxicity, or ANC less than 750/uL or platelet count less than 75 × 10⁹/L on day 21

Next cycle to start once ANC is greater than or equal to 1000/uL and platelet count is greater than or equal to 100 × 10⁹/L.

Although the protocol does not specify, it is assumed that if these thresholds are not met by day 21, the next cycle will start with the dose reductions as specified.

Chemotherapy, part B (cycles 2, 4, 6)

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Methotrexate (MTX) 200 mg/m² IV over 2 hours once on day 1, then 800 mg/m² IV over 22 hours (total dose per cycle: 1000 mg/m²)
Cytarabine (Ara-C) 3000 mg/m² IV over 2 hours every 12 hours on days 3 & 4 (total dose per cycle: 12,000 mg/m²)

Supportive medications

Folinic acid (Leucovorin) (dose/timing not specified) until serum methotrexate level less than 100 nmol/L
Sodium bicarbonate 1300 mg PO twice per day until methotrexate level less than 100 nmol/L
Filgrastim (Neupogen) or Pegfilgrastim (Neulasta) starting 24 to 48 hours after completion of chemotherapy
Ciprofloxacin (Cipro) 500 mg PO twice per day for 10 days after chemotherapy
Fluconazole (Diflucan) 100 mg PO once per day for 10 days after chemotherapy
Valacyclovir (Valtrex) 500 mg PO once per day for 10 days after chemotherapy

Dose modifications

Methotrexate (MTX) reduced by 25% in subsequent B cycles if neutropenic fever occurs, grade 3/4 non-hematological toxicity, or ANC less than 750/uL or platelet count less than 75 × 10⁹/L on day 21
Cytarabine (Ara-C) reduced by 33% in subsequent B cycles if neutropenic fever occurs, grade 3/4 non-hematological toxicity, or ANC less than 750/uL or platelet count less than 75 × 10⁹/L on day 21

21-day cycles

CNS prophylaxis

"Recommended in patients with paraspinal disease, paranasal sinus disease, testicular disease, bone marrow disease, diffuse osseous disease or greater than or equal to 2 sites of extranodal disease. Actual administration of prophylactic intrathecal chemotherapy was at the treating physician's discretion."

References

Oki Y, Westin JR, Vega F, Chuang H, Fowler N, Neelapu S, Hagemeister FB, McLaughlin P, Kwak LW, Romaguera JE, Fanale M, Younes A, Rodriguez MA, Orlowski RZ, Wang M, Ouzounian ST, Samaniego F, Fayad L. Prospective phase II study of rituximab with alternating cycles of hyper-CVAD and high-dose methotrexate with cytarabine for young patients with high-risk diffuse large B-cell lymphoma. Br J Haematol. 2013 Dec;163(5):611-20. Epub 2013 Oct 1. link to original article contains verified protocol link to PMC article PubMed
Retrospective: Howlett C, Snedecor SJ, Landsburg DJ, Svoboda J, Chong EA, Schuster SJ, Nasta SD, Feldman T, Rago A, Walsh KM, Weber S, Goy A, Mato A. Front-line, dose-escalated immunochemotherapy is associated with a significant progression-free survival advantage in patients with double-hit lymphomas: a systematic review and meta-analysis. Br J Haematol. 2015 Aug;170(4):504-14. Epub 2015 Apr 24. link to original article PubMed

R-MegaCHOP-14

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R-MegaCHOP-14: Rituximab, "Mega" (high-dose) Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne every 14 days

Regimen

Study	Evidence	Comparator	Comparative Efficacy
Chiappella et al. 2017 (DLCL04)	Phase III (E-esc)	1. R-CHOP-14	Not reported
Chiappella et al. 2017 (DLCL04)	Phase III (E-esc)	2. R-CHOP-14, then R-MAD, then BEAM, then auto HSCT 3. R-MegaCHOP-14, then R-MAD, then BEAM, then auto HSCT	Did not meet primary endpoint of FFS24

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 1200 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 70 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² IV once on day 1
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

14-day cycle for 6 cycles

References

Chiappella A, Martelli M, Angelucci E, Brusamolino E, Evangelista A, Carella AM, Stelitano C, Rossi G, Balzarotti M, Merli F, Gaidano G, Pavone V, Rigacci L, Zaja F, D'Arco A, Cascavilla N, Russo E, Castellino A, Gotti M, Congiu AG, Cabras MG, Tucci A, Agostinelli C, Ciccone G, Pileri SA, Vitolo U. Rituximab-dose-dense chemotherapy with or without high-dose chemotherapy plus autologous stem-cell transplantation in high-risk diffuse large B-cell lymphoma (DLCL04): final results of a multicentre, open-label, randomised, controlled, phase 3 study. Lancet Oncol. 2017 Aug;18(8):1076-1088. Epub 2017 Jun 28. link to original article contains protocol PubMed

R-miniCEOP

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R-miniCEOP: Rituximab, mini, Cyclophosphamide, Epirubicin, O?? (vinblastine), Prednisone

Regimen

Study	Evidence	Comparator	Comparative Efficacy
Merli et al. 2012 (ANZINTER3)	Phase III (E-de-esc)	R-CHOP	Did not meet primary endpoint of EFS

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Epirubicin (Ellence) 50 mg/m² IV once on day 1
Vinblastine (Velban) 5 mg/m² IV once on day 1
Prednisone (Sterapred) 50 mg/m² IV or PO once per day on days 1 to 5

Supportive medications

Prophylactic G-CSF used for persisting grade 4 neutropenia or febrile neutropenia.
Cotrimoxazole (dose/route/schedule not specified) prophylaxis.
Erythropoietin use was allowed for hemoglobin less than 11 g/dL.

21-day cycle for 6 cycles

Subsequent treatment

Patients with initial bulky disease and/or partially responding sites received radiothearpy

References

ANZINTER3: Merli F, Luminari S, Rossi G, Mammi C, Marcheselli L, Tucci A, Ilariucci F, Chiappella A, Musso M, Di Rocco A, Stelitano C, Alvarez I, Baldini L, Mazza P, Salvi F, Arcari A, Fragasso A, Gobbi PG, Liberati AM, Federico M. Cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab versus epirubicin, cyclophosphamide, vinblastine, prednisone and rituximab for the initial treatment of elderly "fit" patients with diffuse large B-cell lymphoma: results from the ANZINTER3 trial of the Intergruppo Italiano Linfomi. Leuk Lymphoma. 2012 Apr;53(4):581-8. Epub 2011 Nov 15. link to original article contains verified protocol PubMed

Untreated, non-randomized or retrospective data

BR

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BR: Bendamustine, Rituximab

Regimen variant #1, 90 mg/m²

Study	Evidence
Park et al. 2016 (LCCC 1011)	Phase II

Note: this dosing was intended for patients with ECOG PS = 3 at baseline.

Chemotherapy

Bendamustine 90 mg/m² IV once per day on days 1 & 2, given first on day 1
- Dose increased to 120 mg/m² if ECOG PS improved to less than or equal to 2 after 3 cycles
Rituximab (Rituxan) 375 mg/m² IV once on day 1, given second

21-day cycle for up to 8 cycles

Regimen variant #2, 120 mg/m²

Study	Evidence
Park et al. 2016 (LCCC 1011)	Phase II

Chemotherapy

Bendamustine 120 mg/m² IV once per day on days 1 & 2, given first on day 1
Rituximab (Rituxan) 375 mg/m² IV once on day 1, given second

21-day cycle for up to 8 cycles

References

LCCC 1011: Park SI, Grover NS, Olajide O, Asch AS, Wall JG, Richards KL, Sobol AL, Deal AM, Ivanova A, Foster MC, Muss HB, Shea TC. A phase II trial of bendamustine in combination with rituximab in older patients with previously untreated diffuse large B-cell lymphoma. Br J Haematol. 2016 Oct;175(2):281-289. link to original article contains verified protocol link to PMC article PubMed

Helicobacter pylori eradication therapy

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Regimen variant #1, before 1996

Study	Evidence
Kuo et al. 2012	Non-randomized

Note: This regimen is intended for the treatment of gastric DLBCL only; H. pylori eradication would not be an appropriate treatment for systemic DLBCL.

Antibiotic therapy

Amoxicillin 500 mg PO every 6 hours
Metronidazole (Flagyl) 250 mg PO every 6 hours
One of the following:
- Bismuth subcitrate 120 mg PO every 6 hours
- Omeprazole (Prilosec) 20 mg PO twice per day

28-day course

Regimen variant #2, after 1996

Study	Evidence
Kuo et al. 2012	Non-randomized

Note: This regimen is intended for the treatment of gastric DLBCL only; H. pylori eradication would not be an appropriate treatment for systemic DLBCL.

Antibiotic therapy

Amoxicillin 500 mg PO every 6 hours
Clarithromycin (Biaxin) 500 mg PO twice per day
Omeprazole (Prilosec) 20 mg PO twice per day

14-day course

References

Kuo SH, Yeh KH, Wu MS, Lin CW, Hsu PN, Wang HP, Chen LT, Cheng AL. Helicobacter pylori eradication therapy is effective in the treatment of early-stage H pylori-positive gastric diffuse large B-cell lymphomas. Blood. 2012 May 24;119(21):4838-44. Epub 2012 Mar 7. link to original article PubMed

O-miniCHOP

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O-miniCHOP: Ofatumumab, reduced-dose (mini) Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne

Regimen

Study	Evidence
Peyrade et al. 2017 (LYSA LNH09-7B)	Phase II

Preceding treatment

Pre-phase vincristine & prednisone

Chemotherapy

Ofatumumab (Arzerra) 1000 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 400 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 25 mg/m² IV once on day 1
Vincristine (Oncovin) 1 mg IV once on day 1
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 5

Supportive medications

Acetaminophen (Tylenol) 1000 mg PO once on day 1, prior to Ofatumumab (Arzerra)
Diphenhydramine (Benadryl) 50 mg (route not specified) once on day 1, prior to Ofatumumab (Arzerra)

21-day cycle for 6 cycles

References

Peyrade F, Bologna S, Delwail V, Emile JF, Pascal L, Fermé C, Schiano JM, Coiffier B, Corront B, Farhat H, Fruchart C, Ghesquieres H, Macro M, Tilly H, Choufi B, Delarue R, Fitoussi O, Gabarre J, Haioun C, Jardin F. Combination of ofatumumab and reduced-dose CHOP for diffuse large B-cell lymphomas in patients aged 80 years or older: an open-label, multicentre, single-arm, phase 2 trial from the LYSA group. Lancet Haematol. 2017 Jan;4(1):e46-e55. link to original article contains protocol PubMed

R-BL

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R-BL: Rituximab, Bendamustine, Lenalidomide

Regimen

Study	Evidence	Efficacy
Hitz et al. 2016 (SAKK 38/08)	Phase II, <20 pts in subgroup	ORR: 61% (95% CI 45-76%)

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Bendamustine 70 mg/m² IV once per day on days 1 & 2
Lenalidomide (Revlimid) 10 mg PO once per day on days 1 to 21

28-day cycle for 6 cycles

References

Hitz F, Zucca E, Pabst T, Fischer N, Cairoli A, Samaras P, Caspar CB, Mach N, Krasniqi F, Schmidt A, Rothermundt C, Enoiu M, Eckhardt K, Berardi Vilei S, Rondeau S, Mey U. Rituximab, bendamustine and lenalidomide in patients with aggressive B-cell lymphoma not eligible for anthracycline-based therapy or intensive salvage chemotherapy - SAKK 38/08. Br J Haematol. 2016 Jul;174(2):255-63. Epub 2016 Mar 28. link to original article contains protocol PubMed

R-CDOP

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R-CDOP: Rituximab, Cyclophosphamide, Doxil (Pegylated liposomal doxorubicin), Oncovin (Vincristine), Prednisone
DRCOP: Doxil (Pegylated liposomal doxorubicin), Rituximab, Cyclophosphamide, Oncovin (Vincristine), Prednisone

Regimen variant #1

Study	Evidence
Oki et al. 2014 (MDACC 2004-0305)	Phase II

Chemotherapy

Pegylated liposomal doxorubicin (Doxil) 40 mg/m² (maximum dose of 90 mg) IV over 60 minutes once on day 1
Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Vincristine (Oncovin) 2 mg IV once on day 1
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 5

Supportive medications

Filgrastim (Neupogen) 5 mcg/kg SC once per day from day 2 until ANC greater than 3000/μl

OR

Pegfilgrastim (Neulasta) 6 mg SC once on day 2

Dose modifications

Dose reduction level 1 (see paper for triggers):
- Pegylated liposomal doxorubicin (Doxil) reduced to 35 mg/m²
- Cyclophosphamide (Cytoxan) reduced to 600 mg/m²
Dose reduction level 2 (see paper for triggers):
- Pegylated liposomal doxorubicin (Doxil) reduced to 30 mg/m²
- Cyclophosphamide (Cytoxan) reduced to 450 mg/m²

21-day cycle for 6 to 8 cycles

Regimen variant #2

Study	Evidence
Zaja et al. 2006	Phase II

Only the dose of liposomal doxorubicin and number of cycles used was specified in the abstract. The doses of the other medications and schedule are provided based on the standard R-CHOP regimen, whose references can be found on this page.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Pegylated liposomal doxorubicin (Doxil) 30 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

21-day cycle for 6 cycles

References

Zaja F, Tomadini V, Zaccaria A, Lenoci M, Battista M, Molinari AL, Fabbri A, Battista R, Cabras MG, Gallamini A, Fanin R. CHOP-rituximab with pegylated liposomal doxorubicin for the treatment of elderly patients with diffuse large B-cell lymphoma. Leuk Lymphoma. 2006 Oct;47(10):2174-80. link to original article PubMed
MDACC 2004-0305: Oki Y, Ewer MS, Lenihan DJ, Fisch MJ, Hagemeister FB, Fanale M, Romaguera J, Pro B, Fowler N, Younes A, Astrow AB, Huang X, Kwak LW, Samaniego F, McLaughlin P, Neelapu SS, Wang M, Fayad LE, Durand JB, Rodriguez MA. Pegylated liposomal doxorubicin replacing conventional doxorubicin in standard R-CHOP chemotherapy for elderly patients with diffuse large B-cell lymphoma: an open label, single arm, phase II trial. Clin Lymphoma Myeloma Leuk. 2015 Mar;15(3):152-8. Epub 2014 Sep 28. link to original article contains verified protocol link to PMC article PubMed

R-CEOP90 (Epirubicin)

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R-CEOP90: Rituximab, Cyclophosphamide, Epirubicin (90 mg/m² dosing), Oncovin (Vincristine), Prednisone

Regimen variant #1, 4 cycles

Study	Evidence
Cai et al. 2014	Phase II

This regimen is intended to reduce cardiotoxicity and was not just for patients with contraindicated doxorubicin. Note that the cycle length is not explicitly defined in the paper but was reported as a median of 21 days (range 21 to 33 days).

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 2
Epirubicin (Ellence) 90 mg/m² IV once on day 2
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 2
Prednisolone (Millipred) 100 mg/day PO on days 2 to 6

21-day cycle for 4 cycles

Subsequent treatment

Patients with stage IA or IIA disease with bulky disease and extranodal and residual masses: IFRT, 30 to 45 Gy

Regimen variant #2, 6 cycles

Study	Evidence
Cai et al. 2014	Phase II

This regimen is intended to reduce cardiotoxicity and was not just for patients with contraindicated doxorubicin. Note that the cycle length is not explicitly defined in the paper but was reported as a median of 21 days (range 21 to 33 days).

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 2
Epirubicin (Ellence) 90 mg/m² IV once on day 2
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 2
Prednisolone (Millipred) 100 mg/day PO on days 2 to 6

'21-day cycle for 6 cycles

References

Cai QC, Gao Y, Wang XX, Cai QQ, Lin ZX, Bai B, Guo Y, Huang HQ. Long-term results of the R-CEOP90 in the treatment of young patients with chemotherapy-naïve diffuse large B cell lymphoma: a phase II study. Leuk Lymphoma. 2014 Oct;55(10):2387-8. link to original article contains verified protocol PubMed

R-CEOP (Etoposide)

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R-CEOP: Rituximab, Cyclophosphamide, Etoposide, Oncovin (Vincristine), Prednisone

Regimen

Study	Evidence
Moccia et al. 2009	Retrospective

This regimen is intended for patients with a contraindication to anthracyclines. Only the dose of etoposide and number of cycles used was specified in the abstract. The doses of the other medications and schedule are provided based on the standard R-CHOP regimen, whose references can be found on this page.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Etoposide (Vepesid) 50 mg/m² IV once on day 1, then 100 mg/m² PO once per day on days 2 & 3
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
- Alternate dosing used in the R-CHOP regimens described in Coiffier et al. 2002 & 2010; Feugier et al. 2005; Mounier et al. 2012 - LNH 98-5 is Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 5

21-day cycle for 3 to 4 cycles +/- radiation therapy for patients with limited stage disease; 6 cycles for patients with advanced stage disease

References

Retrospective: Abstract: Moccia, Alden A., Schaff, Kimberly, Hoskins, Paul, Klasa, Richard, Savage, Kerry J., Shenkier, Tamara, Gascoyne, Randy D., Connors, Joseph M., Sehn, Laurie H. R-CHOP with Etoposide Substituted for Doxorubicin (R-CEOP): Excellent Outcome in Diffuse Large B Cell Lymphoma for Patients with a Contraindication to Anthracyclines. ASH Annual Meeting Abstracts 2009 114: 408 link to abstract

R-CHMP

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R-CHMP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Marqibo (Vincristine liposomal), Prednisone

Regimen variant #1, 3 cycles

Study	Evidence
Hagemeister et al. 2013	Phase II

This regimen was intended for stage I patients with no LN greater than 5 cm.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Pegylated liposomal doxorubicin (Doxil) 50 mg/m² IV once on day 1
Vincristine liposomal (Marqibo) 2 mg/m² IV once on day 1
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

21-day cycle for 3 cycles

Subsequent treatment

RT

Regimen variant #2, 6 cycles

Study	Evidence
Hagemeister et al. 2013	Phase II

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Pegylated liposomal doxorubicin (Doxil) 50 mg/m² IV once on day 1
Vincristine liposomal (Marqibo) 2 mg/m² IV once on day 1
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

21-day cycle for 6 cycles

References

Hagemeister F, Rodriguez MA, Deitcher SR, Younes A, Fayad L, Goy A, Dang NH, Forman A, McLaughlin P, Medeiros LJ, Pro B, Romaguera J, Samaniego F, Silverman JA, Sarris A, Cabanillas F. Long term results of a phase 2 study of vincristine sulfate liposome injection (Marqibo(®) ) substituted for non-liposomal vincristine in cyclophosphamide, doxorubicin, vincristine, prednisone with or without rituximab for patients with untreated aggressive non-Hodgkin lymphomas. Br J Haematol. 2013 Sep;162(5):631-8. Epub 2013 Jun 27. link to original article contains verified protocol PubMed

R-GCVP

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R-GCVP: Rituximab, Gemcitabine, Cyclophosphamide, Vincristine, Prednisolone

Regimen

Study	Evidence
Fields et al. 2013 (UCL/05/154)	Phase II

Intended for use in patients unlikely to tolerate anthracyclines due to cardiac comorbidity.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Gemcitabine (Gemzar) as follows:
- Cycle 1: 750 mg/m² IV over 30 minutes once per day on days 1 & 8
- Cycle 2: 875 mg/m² IV over 30 minutes once per day on days 1 & 8
- Cycles 3 to 6: 1000 mg/m² IV over 30 minutes once per day on days 1 & 8
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisolone (Millipred) 100 mg PO once per day on days 1 to 5

Supportive medications

Acetaminophen (Tylenol) 1000 mg (route not specified) once on day 1, prior to Rituximab (Rituxan)
Chlorpheniramine (Chlor-Trimeton) 10 mg IV once on day 1, prior to Rituximab (Rituxan)
Pegfilgrastim (Neulasta) 6 mg SC once on day 9

CNS prophylaxis

Methotrexate (MTX) 12.5 mg IT x 3 cycles (timing not specified) for patients at high risk of CNS relapse

21-day cycle for 6 cycles

References

UCL/05/154: Fields PA, Townsend W, Webb A, Counsell N, Pocock C, Smith P, Jack A, El-Mehidi N, Johnson PW, Radford J, Linch DC, Cunningham D. De novo treatment of diffuse large B-cell lymphoma with rituximab, cyclophosphamide, vincristine, gemcitabine, and prednisolone in patients with cardiac comorbidity: a United kingdom national cancer research institute trial. J Clin Oncol. 2014 Feb 1;32(4):282-7. Epub 2013 Nov 12. link to original article contains verified protocol PubMed

R-MegaCHOP

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R-MegaCHOP: Rituximab, Mega, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne

Regimen

Study	Evidence
Pardal et al. 2014 (GELTAMO-2006)	Phase II

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 1500 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 65 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² IV once on day 1
Prednisone (Sterapred) 60 mg/m² PO once per day on days 1 to 5

Supportive medications

Pegfilgrastim (Neulasta) given after each cycle

21-day cycle for 3 cycles

Subsequent treatment

Negative PET-CT after 3 cycles: another 3 cycles of R-MegaCHOP for a total of 6 cycles
Positive PET-CT after 3 cycles: R-IFE

References

GELTAMO-2006: Pardal E, Coronado M, Martín A, Grande C, Marín-Niebla A, Panizo C, Bello JL, Conde E, Hernández MT, Arranz R, Bargay J, González-Barca E, Pérez-Ceballos E, Montes-Moreno S, Caballero MD. Intensification treatment based on early FDG-PET in patients with high-risk diffuse large B-cell lymphoma: a phase II GELTAMO trial. Br J Haematol. 2014 Nov;167(3):327-36. Epub 2014 Jul 28. link to original article contains verified protocol PubMed

R-miniCHOP

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R-miniCHOP: Rituximab, reduced-dose (mini) Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne

Regimen

Study	Evidence
Peyrade et al. 2011	Phase II

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 400 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 25 mg/m² IV once on day 1
Vincristine (Oncovin) 1 mg IV once on day 1
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 5
- No dose adjustments for hematologic toxicity. If needed, the subsequent R-miniCHOP cycle was postponed until ANC was greater than or equal to 1000/uL and platelet count was greater than or equal to 100 x 10⁹/L, with a maximum of 28 days between cycles. Treatment was stopped if patients' counts were not adequate within 28 days.

Supportive medications

"Prevention of tumour lysis syndrome by alkalinisation or hypouricaemic drugs was done if necessary."
Serotonin (5-HT3) antagonist given every cycle.
Prophylactic G-CSF or erythropoietin was left to treating physician's discretion.
- Patients with severe neutropenia or neutropenic fever received G-CSF (dose not specified) SC once per day on days 6 to 13 of the subsequent cycle until ANC is greater than or equal to 1000/uL.

21-day cycle for 6 cycles

References

Peyrade F, Jardin F, Thieblemont C, Thyss A, Emile JF, Castaigne S, Coiffier B, Haioun C, Bologna S, Fitoussi O, Lepeu G, Fruchart C, Bordessoule D, Blanc M, Delarue R, Janvier M, Salles B, André M, Fournier M, Gaulard P, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte (GELA) investigators. Attenuated immunochemotherapy regimen (R-miniCHOP) in elderly patients older than 80 years with diffuse large B-cell lymphoma: a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2011 May;12(5):460-8. link to original article contains verified protocol PubMed

R2CHOP

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R2CHOP: Rituximab, Revlimid (Lenalidomide), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne
LR-CHOP-21: Lenalidomide, Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne given every 21 days

Regimen variant #1, len 15 mg/day for 14 d/cycle

Study	Evidence	Efficacy
Vitolo et al. 2014 (REAL07)	Phase II	ORR: 92% (95% CI 81–97)

Note: CNS prophylaxis was offered to "at risk" patients.

Chemotherapy

Lenalidomide (Revlimid) 15 mg PO once per day on days 1 to 14
Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 5

CNS prophylaxis

Methotrexate (MTX) as follows:
- Cycles 1 to 4: 12 mg IT once on day 1

Supportive medications

Granulocyte colony-stimulating factors (dose/duration not specified)
Low-molecular-weight heparins (dose/duration not specified)
PCP prophylaxis with one of the following:
- Trimethoprim-Sulfamethoxazole (Bactrim DS) (dose/duration not specified)
- Pentamidine (Nebupent) (dose/duration not specified)
Carriers of hepatitis B virus: Lamivudine (Epivir) (dose/duration not specified)

21-day cycle for 6 cycles

Regimen variant #2, len 25 mg/day for 10 d/cycle

Study	Evidence	Efficacy
Nowakowski et al. 2014 (Mayo Clinic MC078E)	Phase II	ORR: 98%

Chemotherapy

Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 10
Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) 100 mg/m² PO once per day on days 1 to 5

Supportive medications

Pegfilgrastim (Neulasta) 6 mg SC once on day 2
Aspirin 81 mg PO once per day unless on therapeutic dose Warfarin (Coumadin) or low molecular weight heparin

21-day cycle for up to 6 cycles

References

REAL07: Vitolo U, Chiappella A, Franceschetti S, Carella AM, Baldi I, Inghirami G, Spina M, Pavone V, Ladetto M, Liberati AM, Molinari AL, Zinzani P, Salvi F, Fattori PP, Zaccaria A, Dreyling M, Botto B, Castellino A, Congiu A, Gaudiano M, Zanni M, Ciccone G, Gaidano G, Rossi G; Fondazione Italiana Linfomi. Lenalidomide plus R-CHOP21 in elderly patients with untreated diffuse large B-cell lymphoma: results of the REAL07 open-label, multicentre, phase 2 trial. Lancet Oncol. 2014 Jun;15(7):730-7. Epub 2014 May 12. link to original article contains verified protocol PubMed
Mayo Clinic MC078E: Nowakowski GS, LaPlant B, Macon WR, Reeder CB, Foran JM, Nelson GD, Thompson CA, Rivera CE, Inwards DJ, Micallef IN, Johnston PB, Porrata LF, Ansell SM, Gascoyne RD, Habermann TM, Witzig TE. Lenalidomide combined with R-CHOP overcomes negative prognostic impact of non-germinal center B-cell phenotype in newly diagnosed diffuse large B-cell lymphoma: a phase II study. J Clin Oncol. 2015 Jan 20;33(3):251-7. Epub 2014 Aug 18. link to original article contains verified protocol PubMed

Consolidation after upfront therapy

CBV, then auto HSCT

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Regimen

Study	Evidence	Comparator	Comparative Efficacy
Stiff et al. 2013 (SWOG S9704)	Phase III (E-esc)	R-CHOP x 8	Superior PFS

Preceding treatment

R-CHOP x 6

Autologous HSCT conditioning regimens

References

SWOG S9704: Stiff PJ, Unger JM, Cook JR, Constine LS, Couban S, Stewart DA, Shea TC, Porcu P, Winter JN, Kahl BS, Miller TP, Tubbs RR, Marcellus D, Friedberg JW, Barton KP, Mills GM, LeBlanc M, Rimsza LM, Forman SJ, Fisher RI. Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. N Engl J Med. 2013 Oct 31;369(18):1681-90. link to original article link to PMC article PubMed
1. Subgroup analysis: Puvvada SD, Stiff PJ, Leblanc M, Cook JR, Couban S, Leonard JP, Kahl B, Marcellus D, Shea TC, Winter JN, Li H, Rimsza LM, Friedberg JW, Smith SM. Outcomes of MYC-associated lymphomas after R-CHOP with and without consolidative autologous stem cell transplant: subset analysis of randomized trial intergroup SWOG S9704. Br J Haematol. 2016 Sep;174(5):686-91. Epub 2016 Apr 13. link to original article link to PMC article PubMed

CBVM, then auto HSCT

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Regimen

Study	Evidence
Haioun et al. 2009 (LNH 98-3)	Non-randomized portion of RCT

Preceding treatment

ACE versus ACVBP

Chemotherapy

Stem cells reinfused afterwards (unclear which day)

Subsequent treatment

Observation versus rituximab maintenance

References

LNH 98-3: Haioun C, Mounier N, Emile JF, Ranta D, Coiffier B, Tilly H, Récher C, Fermé C, Gabarre J, Herbrecht R, Morchhauser F, Gisselbrecht C. Rituximab versus observation after high-dose consolidative first-line chemotherapy with autologous stem-cell transplantation in patients with poor-risk diffuse large B-cell lymphoma. Ann Oncol. 2009 Dec;20(12):1985-92. Epub 2009 Jun 30. link to original article contains verified protocol PubMed

Cytarabine monotherapy

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Regimen

Study	Evidence
Récher et al. 2011 (LNH03-2B)	Non-randomized portion of RCT
Ketterer et al. 2013 (LNH03-1B)	Non-randomized portion of RCT

Preceding treatment

REI consolidation x 4

Chemotherapy

Cytarabine (Ara-C) 100 mg/m² SC once per day on days 1 to 4

14-day cycle for 2 cycles

References

LNH03-2B: Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, Thiéblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquières H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011 Nov 26;378(9806):1858-67. link to original article contains verified protocol PubMed
1. Subgroup analysis: Molina TJ, Canioni D, Copie-Bergman C, Recher C, Brière J, Haioun C, Berger F, Fermé C, Copin MC, Casasnovas O, Thieblemont C, Petrella T, Leroy K, Salles G, Fabiani B, Morschauser F, Mounier N, Coiffier B, Jardin F, Gaulard P, Jais JP, Tilly H. Young patients with non-germinal center B-cell-like diffuse large B-cell lymphoma benefit from intensified chemotherapy with ACVBP plus rituximab compared with CHOP plus rituximab: analysis of data from the Groupe d'Etudes des Lymphomes de l'Adulte/lymphoma study association phase III trial LNH 03-2B. J Clin Oncol. 2014 Dec 10;32(35):3996-4003. Epub 2014 Nov 10. link to original article PubMed
LNH03-1B: Ketterer N, Coiffier B, Thieblemont C, Fermé C, Brière J, Casasnovas O, Bologna S, Christian B, Connerotte T, Récher C, Bordessoule D, Fruchart C, Delarue R, Bonnet C, Morschhauser F, Anglaret B, Soussain C, Fabiani B, Tilly H, Haioun C. Phase III study of ACVBP versus ACVBP plus rituximab for patients with localized low-risk diffuse large B-cell lymphoma (LNH03-1B). Ann Oncol. 2013 Apr;24(4):1032-7. Epub 2012 Dec 12. link to original article PubMed

Ibritumomab tiuxetan monotherapy

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Regimen variant #1, no cap

Study	Evidence
Witzig et al. 2015 (ECOG E3402)	Phase II

Preceding treatment

R-CHOP x 4 to 6

Radioimmunotherapy

Rituximab (Rituxan) 250 mg/m² IV once per day on days 1 & 8
Ibritumomab tiuxetan & Yttrium-90 (Zevalin) 14.8 MBq/kg IV once on day 8

8-day course

Subsequent treatment

Patients with CT or PET positive disease 12 weeks after radioimmunotherapy: 30 Gy of IFRT

Regimen variant #2, capped dose

Study	Evidence
Persky et al. 2014 (SWOG S0313)	Phase II

Preceding treatment

CHOP x 3, then IFRT

Radioimmunotherapy

Rituximab (Rituxan) 250 mg/m² IV once per day on days 1 & 8 +/- 1 day, given first on day 7, 8, or 9
Ibritumomab tiuxetan & Yttrium-90 (Zevalin) 0.4 mCi/kg (maximum dose of 32 mCi) IV once on day 8 +/- 1 day, given second, within 4 hours of rituximab

References

SWOG S0313: Persky DO, Miller TP, Unger JM, Spier CM, Puvvada S, Stea BD, Press OW, Constine LS, Barton KP, Friedberg JW, LeBlanc M, Fisher RI. Ibritumomab consolidation after 3 cycles of CHOP plus radiotherapy in high-risk limited-stage aggressive B-cell lymphoma: SWOG S0313. Blood. 2015 Jan 8;125(2):236-41. Epub 2014 Nov 13. link to original article contains verified protocol link to PMC article PubMed
ECOG E3402: Witzig TE, Hong F, Micallef IN, Gascoyne RD, Dogan A, Wagner H Jr, Kahl BS, Advani RH, Horning SJ. A phase II trial of RCHOP followed by radioimmunotherapy for early stage (stages I/II) diffuse large B-cell non-Hodgkin lymphoma: ECOG3402. Br J Haematol. 2015 Sep;170(5):679-86. Epub 2015 May 14. link to original article contains verified protocol link to PMC article PubMed

Methotrexate monotherapy

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Regimen

Study	Evidence
Récher et al. 2011 (LNH03-2B)	Non-randomized portion of RCT
Ketterer et al. 2013 (LNH03-1B)	Non-randomized portion of RCT

Preceding treatment

ACVBP-R induction x 4

Chemotherapy

Methotrexate (MTX) 3000 mg/m² IV once on day 1

Supportive medications

Calcium folinate - Folinic acid (Leucovorin) rescue

14-day cycle for 2 cycles

Subsequent treatment

REI consolidation, in 2 weeks

References

LNH03-2B: Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, Thiéblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquières H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011 Nov 26;378(9806):1858-67. link to original article contains verified protocol PubMed
1. Subgroup analysis: Molina TJ, Canioni D, Copie-Bergman C, Recher C, Brière J, Haioun C, Berger F, Fermé C, Copin MC, Casasnovas O, Thieblemont C, Petrella T, Leroy K, Salles G, Fabiani B, Morschauser F, Mounier N, Coiffier B, Jardin F, Gaulard P, Jais JP, Tilly H. Young patients with non-germinal center B-cell-like diffuse large B-cell lymphoma benefit from intensified chemotherapy with ACVBP plus rituximab compared with CHOP plus rituximab: analysis of data from the Groupe d'Etudes des Lymphomes de l'Adulte/lymphoma study association phase III trial LNH 03-2B. J Clin Oncol. 2014 Dec 10;32(35):3996-4003. Epub 2014 Nov 10. link to original article PubMed
LNH03-1B: Ketterer N, Coiffier B, Thieblemont C, Fermé C, Brière J, Casasnovas O, Bologna S, Christian B, Connerotte T, Récher C, Bordessoule D, Fruchart C, Delarue R, Bonnet C, Morschhauser F, Anglaret B, Soussain C, Fabiani B, Tilly H, Haioun C. Phase III study of ACVBP versus ACVBP plus rituximab for patients with localized low-risk diffuse large B-cell lymphoma (LNH03-1B). Ann Oncol. 2013 Apr;24(4):1032-7. Epub 2012 Dec 12. link to original article PubMed

Observation

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Regimen

Study	Evidence	Comparator	Comparative Efficacy
Horning et al. 2004 (ECOG E1484)	Phase III (C)	IFRT	Seems to have inferior DFS
Habermann et al. 2006 (ECOG E4494/CALGB 9793)	Phase III (C)	Rituximab	Did not meet primary endpoint of FFS
Bonnet et al. 2007	Phase III (E-de-esc)	IFRT	Did not meet primary endpoint of EFS
Haioun et al. 2009 (LNH 98-3)	Phase III (C)	Rituximab	Might have inferior EFS
Jaeger et al. 2015 (NHL13)	Phase III (C)	Rituximab	Did not meet primary endpoint of EFS
Witzens-Harig et al. 2015 (HD2002)	Phase III (C)	Rituximab	Inferior OS in males
Lamy et al. 2017 (LYSA/GOELAMS 02-03)	Phase III (C)	IFRT	Non-inferior EFS

No further treatment, also variously termed "observation" and "watchful waiting". Note: in ECOG E4494/CALGB 9793, a statistically signficant disadvantage to observation was seen in the group receiving CHOP induction, which is no longer standard of care.

Preceding treatment

ECOG E1484: CHOP x 8, with CR
ECOG E4494/CALGB 9793: R-CHOP versus CHOP induction
Bonnet et al. 2007: CHOP x 4
LNH 98-3: CBVM, then auto HSCT consolidation
HD2002: "Standard treatment"
LYSA/GOELAMS 02-03: R-CHOP-14 x 4 to 6

References

ECOG E1484: Horning SJ, Weller E, Kim K, Earle JD, O'Connell MJ, Habermann TM, Glick JH. Chemotherapy with or without radiotherapy in limited-stage diffuse aggressive non-Hodgkin's lymphoma: Eastern Cooperative Oncology Group study 1484. J Clin Oncol. 2004 Aug 1;22(15):3032-8. Epub 2004 Jun 21. link to original article PubMed
ECOG E4494/CALGB 9793: Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, Dakhil SR, Woda B, Fisher RI, Peterson BA, Horning SJ. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006 Jul 1;24(19):3121-7. Epub 2006 Jun 5. link to original article contains verified protocol PubMed
Bonnet C, Fillet G, Mounier N, Ganem G, Molina TJ, Thiéblemont C, Fermé C, Quesnel B, Martin C, Gisselbrecht C, Tilly H, Reyes F; Groupe d'Etude des Lymphomes de l'Adulte. CHOP alone compared with CHOP plus radiotherapy for localized aggressive lymphoma in elderly patients: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2007 Mar 1;25(7):787-92. Epub 2007 Jan 16. link to original article contains verified protocol PubMed
LNH 98-3: Haioun C, Mounier N, Emile JF, Ranta D, Coiffier B, Tilly H, Récher C, Fermé C, Gabarre J, Herbrecht R, Morchhauser F, Gisselbrecht C. Rituximab versus observation after high-dose consolidative first-line chemotherapy with autologous stem-cell transplantation in patients with poor-risk diffuse large B-cell lymphoma. Ann Oncol. 2009 Dec;20(12):1985-92. Epub 2009 Jun 30. link to original article PubMed
NHL13: Jaeger U, Trneny M, Melzer H, Praxmarer M, Nawarawong W, Ben Yehuda D, Goldstein D, Mihaljevic B, Ilhan O, Ballova V, Hedenus M, Hsiao LT, Au WY, Burgstaller S, Weidinger G, Keil F, Dittrich C, Skrabs C, Klingler A, Chott A, Fridrik MA, Greil R. Rituximab maintenance for patients with aggressive B-cell lymphoma in first remission: results of the randomized NHL13 trial. Haematologica. 2015 Jul;100(7):955-63. Epub 2015 Apr 24. link to original article contains verified protocol link to PMC article PubMed
HD2002: Witzens-Harig M, Benner A, McClanahan F, Klemmer J, Brandt J, Brants E, Rieger M, Meissner J, Hensel M, Neben K, Dreger P, Lengfelder E, Schmidt-Wolf I, Krämer A, Ho AD. Rituximab maintenance improves survival in male patients with diffuse large B-cell lymphoma: results of the HD2002 prospective multicentre randomized phase III trial. Br J Haematol. 2015 Dec;171(5):710-9. Epub 2015 Oct 9. link to original article PubMed
LYSA/GOELAMS 02-03: Lamy T, Damaj G, Soubeyran P, Gyan E, Cartron G, Bouabdallah K, Gressin R, Cornillon J, Banos A, Le Du K, Benchalal M, Moles MP, Le Gouill S, Fleury J, Godmer P, Maisonneuve H, Deconinck E, Houot R, Laribi K, Marolleau JP, Tournilhac O, Branger B, Devillers A, Vuillez JP, Fest T, Colombat P, Costes V, Szablewski V, Béné MC, Delwail V; LYSA Group. R-CHOP 14 with or without radiotherapy in nonbulky limited-stage diffuse large B-cell lymphoma. Blood. 2018 Jan 11;131(2):174-181. Epub 2017 Oct 23. link to original article contains verified protocol PubMed

Placebo

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Regimen

Study	Evidence	Comparator	Comparative Efficacy
Crump et al. 2016 (PRELUDE)	Phase III (C)	Enzastaurin	Did not meet primary endpoint of DFS
Thieblemont et al. 2017 (REMARC)	Phase III (C)	Lenalidomide	Seems to have inferior PFS
Witzig et al. 2018 (PILLAR-2)	Phase III (C)	Everolimus	Did not meet primary endpoint of DFS

No further antineoplastic treatment.

Preceding treatment

PRELUDE: R-CHOP induction
REMARC: R-CHOP21 or R-CHOP-14 induction

References

PRELUDE: Crump M, Leppä S, Fayad L, Lee JJ, Di Rocco A, Ogura M, Hagberg H, Schnell F, Rifkin R, Mackensen A, Offner F, Pinter-Brown L, Smith S, Tobinai K, Yeh SP, Hsi ED, Nguyen T, Shi P, Hahka-Kemppinen M, Thornton D, Lin B, Kahl B, Schmitz N, Savage KJ, Habermann T. Randomized, double-blind, phase III trial of enzastaurin versus placebo in patients achieving remission after first-line therapy for high-risk diffuse large B-cell lymphoma. J Clin Oncol. 2016 Jul 20;34(21):2484-92. Epub 2016 May 23. link to original article PubMed
REMARC: Thieblemont C, Tilly H, Gomes da Silva M, Casasnovas RO, Fruchart C, Morschhauser F, Haioun C, Lazarovici J, Grosicka A, Perrot A, Trotman J, Sebban C, Caballero D, Greil R, van Eygen K, Cohen AM, Gonzalez H, Bouabdallah R, Oberic L, Corront B, Choufi B, Lopez-Guillermo A, Catalano J, Van Hoof A, Briere J, Cabeçadas J, Salles G, Gaulard P, Bosly A, Coiffier B. Lenalidomide maintenance compared with placebo in responding elderly patients with diffuse large B-cell lymphoma treated with first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol. 2017 Aug 1;35(22):2473-2481. Epub 2017 Apr 20. link to original article contains verified protocol PubMed
PILLAR-2: Witzig TE, Tobinai K, Rigacci L, Ikeda T, Vanazzi A, Hino M, Shi Y, Mayer J, Costa LJ, Bermudez Silva CD, Zhu J, Belada D, Bouabdallah K, Kattan JG, Kuruvilla J, Kim WS, Larouche JF, Ogura M, Ozcan M, Fayad L, Wu C, Fan J, Louveau AL, Voi M, Cavalli F. Adjuvant everolimus in high-risk diffuse large B-cell lymphoma: final results from the PILLAR-2 randomized phase III trial. Ann Oncol. 2018 Mar 1;29(3):707-714. link to original article PubMed

Radiation therapy

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Regimen variant #1, testicular irradiation

Study	Evidence
Vitolo et al. 2011 (IELSG-10)	Phase II

Preceding treatment

R-CHOP x 6 to 8 cycles

Radiotherapy

External beam radiotherapy 25 to 30 Gy to the contralateral testis. For patients with stage II disease, involved-field radiation therapy was added; see paper for details.

Regimen variant #2, IFRT x 30 Gy

Study	Evidence	Comparator	Comparative Efficacy
Horning et al. 2004 (ECOG E1484)	Phase III (E-esc)	Observation	Seems to have superior DFS

Preceding treatment

ECOG E1484: CHOP x 8, with CR

Radiotherapy

IFRT 30 Gy

Regimen variant #3, 36 Gy

Study	Evidence
Pfreundschuh et al. 2004 (NHL-B2)	Non-randomized portion of RCT
Pfreundschuh et al. 2008 (RICOVER-60)	Non-randomized portion of RCT
Schmitz et al. 2012 (DSHNHL 2002-1)	Non-randomized portion of RCT
Pfreundschuh et al. 2014 (SMARTE-R-CHOP-14)	Phase II

Preceding treatment

NHL-B2: CHOEP-14 x 6 versus CHOEP-21 x 6 versus CHOP-14 x 6 versus CHOP-21 x 6
RICOVER-60: CHOP-14 x 6 versus CHOP-14 x 8 versus R-CHOP-14 x 6 versus R-CHOP-14 x 8
DSHNHL 2002-1: R-CHOEP-14 x 8 versus R-MegaCHOEP
SMARTE-R-CHOP-14: R-CHOP-14 x 6

Radiotherapy

External beam radiotherapy 36 Gy in daily fractions

Regimen variant #4, IFRT x 40 Gy

Study	Evidence	Comparator	Comparative Efficacy
Horning et al. 2004 (ECOG E1484)	Non-randomized portion of RCT
Bonnet et al. 2007	Phase III (C)	Observation	Did not meet primary endpoint of EFS
Persky et al. 2014 (SWOG S0313)	Phase II
Lamy et al. 2017 (LYSA/GOELAMS 02-03)	Phase III (C)	Observation	Non-inferior EFS

Preceding treatment

ECOG E1484: CHOP x 8, with PR
SWOG S0313: CHOP x 3, with CR
Bonnet et al. 2007: CHOP x 4
LYSA/GOELAMS 02-03: R-CHOP-14 x 4 to 6

Radiotherapy

External beam radiotherapy 40 Gy in daily fractions of 1.80 to 2.00 Gy

Subsequent treatment

SWOG S0313: Ibritumomab tiuxetan consolidation

Regimen variant #5, IFRT x 40 to 55 Gy

Study	Evidence	Comparator	Comparative Efficacy
Miller et al. 1998 (SWOG S8736)	Phase III (E-switch-ooc)	See link	See link
Pfreundschuh et al. 2006 (NCIC CTG LY.9)	Non-randomized portion of RCT
Persky et al. 2008 (SWOG S0014)	Phase II
Persky et al. 2014 (SWOG S0313)	Phase II

Note: these studies did not specify an exact dose; see papers for details.

Preceding treatment

SWOG S8736 and SWOG S0014: CHOP x 3
NCIC CTG LY.9: CHOP-like therapy x 6 versus R-CHOP-like therapy x 6
SWOG S0313: CHOP x 3, with PR

Radiotherapy

External beam radiotherapy 46 to 50 Gy in daily fractions of 1.80 to 2.00 Gy

Subsequent treatment

SWOG S0313: Ibritumumoab tiuxetan consolidation

References

SWOG S8736: Miller TP, Dahlberg S, Cassady JR, Adelstein DJ, Spier CM, Grogan TM, LeBlanc M, Carlin S, Chase E, Fisher RI. Chemotherapy alone compared with chemotherapy plus radiotherapy for localized intermediate- and high-grade non-Hodgkin's lymphoma. N Engl J Med. 1998 Jul 2;339(1):21-6. link to original article contains verified protocol PubMed
1. Update: Stephens DM, Li H, LeBlanc ML, Puvvada SD, Persky D, Friedberg JW, Smith SM. Continued risk of relapse independent of treatment modality in limited-stage diffuse large B-cell lymphoma: Final and long-term analysis of Southwest Oncology Group study S8736. J Clin Oncol. 2016 Sep 1;34(25):2997-3004. Epub 2016 Jul 5. link to original article link to PMC article PubMed
NHL-B2: Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rübe C, Rudolph C, Reiser M, Hossfeld DK, Eimermacher H, Hasenclever D, Schmitz N, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):634-41. Epub 2004 Mar 11. link to original article contains verified protocol PubMed
ECOG E1484: Horning SJ, Weller E, Kim K, Earle JD, O'Connell MJ, Habermann TM, Glick JH. Chemotherapy with or without radiotherapy in limited-stage diffuse aggressive non-Hodgkin's lymphoma: Eastern Cooperative Oncology Group study 1484. J Clin Oncol. 2004 Aug 1;22(15):3032-8. Epub 2004 Jun 21. link to original article PubMed
LNH 93-01: Reyes F, Lepage E, Ganem G, Molina TJ, Brice P, Coiffier B, Morel P, Ferme C, Bosly A, Lederlin P, Laurent G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte (GELA). ACVBP versus CHOP plus radiotherapy for localized aggressive lymphoma. N Engl J Med. 2005 Mar 24;352(12):1197-205. link to original article PubMed
NCIC CTG LY.9: Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. link to original article PubMed
1. Update: Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N; MabThera International Trial (MInT) Group. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011 Oct;12(11):1013-22. link to original article PubMed
Bonnet C, Fillet G, Mounier N, Ganem G, Molina TJ, Thiéblemont C, Fermé C, Quesnel B, Martin C, Gisselbrecht C, Tilly H, Reyes F; Groupe d'Etude des Lymphomes de l'Adulte. CHOP alone compared with CHOP plus radiotherapy for localized aggressive lymphoma in elderly patients: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2007 Mar 1;25(7):787-92. Epub 2007 Jan 16. link to original article contains verified protocol PubMed
RICOVER-60: Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, Reiser M, Nickenig C, Clemens M, Peter N, Bokemeyer C, Eimermacher H, Ho A, Hoffmann M, Mertelsmann R, Trümper L, Balleisen L, Liersch R, Metzner B, Hartmann F, Glass B, Poeschel V, Schmitz N, Ruebe C, Feller AC, Loeffler M; German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 2008 Feb;9(2):105-16. link to original article contains verified protocol PubMed
SWOG S0014: Persky DO, Unger JM, Spier CM, Stea B, LeBlanc M, McCarty MJ, Rimsza LM, Fisher RI, Miller TP; Southwest Oncology Group. Phase II study of rituximab plus three cycles of CHOP and involved-field radiotherapy for patients with limited-stage aggressive B-cell lymphoma: Southwest Oncology Group study 0014. J Clin Oncol. 2008 May 10;26(14):2258-63. Epub 2008 Apr 14. link to original article does not contain protocol PubMed
IELSG-10: Vitolo U, Chiappella A, Ferreri AJ, Martelli M, Baldi I, Balzarotti M, Bottelli C, Conconi A, Gomez H, Lopez-Guillermo A, Martinelli G, Merli F, Novero D, Orsucci L, Pavone V, Ricardi U, Storti S, Gospodarowicz MK, Cavalli F, Sarris AH, Zucca E. First-line treatment for primary testicular diffuse large B-cell lymphoma with rituximab-CHOP, CNS prophylaxis, and contralateral testis irradiation: final results of an international phase II trial. J Clin Oncol. 2011 Jul 10;29(20):2766-72. Epub 2011 Jun 6. link to original article contains verified protocol PubMed
DSHNHL 2002-1: Schmitz N, Nickelsen M, Ziepert M, Haenel M, Borchmann P, Schmidt C, Viardot A, Bentz M, Peter N, Ehninger G, Doelken G, Ruebe C, Truemper L, Rosenwald A, Pfreundschuh M, Loeffler M, Glass B; for the German High-Grade Lymphoma Study Group (DSHNHL). Conventional chemotherapy (CHOEP-14) with rituximab or high-dose chemotherapy (MegaCHOEP) with rituximab for young, high-risk patients with aggressive B-cell lymphoma: an open-label, randomised, phase 3 trial (DSHNHL 2002-1). Lancet Oncol. 2012 Dec;13(12):1250-1259. Epub 2012 Nov 16. link to original article PubMed
SWOG S0313: Persky DO, Miller TP, Unger JM, Spier CM, Puvvada S, Stea BD, Press OW, Constine LS, Barton KP, Friedberg JW, LeBlanc M, Fisher RI. Ibritumomab consolidation after 3 cycles of CHOP plus radiotherapy in high-risk limited-stage aggressive B-cell lymphoma: SWOG S0313. Blood. 2015 Jan 8;125(2):236-41. Epub 2014 Nov 13. link to original article contains verified protocol link to PMC article PubMed
SMARTE-R-CHOP-14: Pfreundschuh M, Poeschel V, Zeynalova S, Hänel M, Held G, Schmitz N, Viardot A, Dreyling MH, Hallek M, Mueller C, Wiesen MH, Witzens-Harig M, Truemper L, Keller U, Rixecker T, Zwick C, Murawski N. Optimization of rituximab for the treatment of diffuse large B-cell lymphoma (II): extended rituximab exposure time in the SMARTE-R-CHOP-14 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group. J Clin Oncol. 2014 Dec 20;32(36):4127-33. Epub 2014 Nov 17. Erratum in: J Clin Oncol. 2015 Jun 10;33(17):1991. link to original article contains verified protocol PubMed
LYSA/GOELAMS 02-03: Lamy T, Damaj G, Soubeyran P, Gyan E, Cartron G, Bouabdallah K, Gressin R, Cornillon J, Banos A, Le Du K, Benchalal M, Moles MP, Le Gouill S, Fleury J, Godmer P, Maisonneuve H, Deconinck E, Houot R, Laribi K, Marolleau JP, Tournilhac O, Branger B, Devillers A, Vuillez JP, Fest T, Colombat P, Costes V, Szablewski V, Béné MC, Delwail V; LYSA Group. R-CHOP 14 with or without radiotherapy in nonbulky limited-stage diffuse large B-cell lymphoma. Blood. 2018 Jan 11;131(2):174-181. Epub 2017 Oct 23. link to original article contains verified protocol PubMed

R-IFE

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R-IFE: Rituximab, IFosfamide, Etoposide
REI: Rituximab, Etoposide, Ifosfamide

Regimen

Study	Evidence
Récher et al. 2011 (LNH03-2B)	Non-randomized portion of RCT
Ketterer et al. 2013 (LNH03-1B)	Non-randomized portion of RCT

Preceding treatment

Methotrexate consolidation x 2

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Etoposide (Vepesid) 300 mg/m² IV once on day 1
Ifosfamide (Ifex) 1500 mg/m² IV once on day 1

14-day cycle for 4 cycles

Subsequent treatment

Cytarabine consolidation, in 2 weeks

References

LNH03-2B: Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, Thiéblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquières H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011 Nov 26;378(9806):1858-67. link to original article contains verified protocol PubMed
1. Subgroup analysis: Molina TJ, Canioni D, Copie-Bergman C, Recher C, Brière J, Haioun C, Berger F, Fermé C, Copin MC, Casasnovas O, Thieblemont C, Petrella T, Leroy K, Salles G, Fabiani B, Morschauser F, Mounier N, Coiffier B, Jardin F, Gaulard P, Jais JP, Tilly H. Young patients with non-germinal center B-cell-like diffuse large B-cell lymphoma benefit from intensified chemotherapy with ACVBP plus rituximab compared with CHOP plus rituximab: analysis of data from the Groupe d'Etudes des Lymphomes de l'Adulte/lymphoma study association phase III trial LNH 03-2B. J Clin Oncol. 2014 Dec 10;32(35):3996-4003. Epub 2014 Nov 10. link to original article PubMed
LNH03-1B: Ketterer N, Coiffier B, Thieblemont C, Fermé C, Brière J, Casasnovas O, Bologna S, Christian B, Connerotte T, Récher C, Bordessoule D, Fruchart C, Delarue R, Bonnet C, Morschhauser F, Anglaret B, Soussain C, Fabiani B, Tilly H, Haioun C. Phase III study of ACVBP versus ACVBP plus rituximab for patients with localized low-risk diffuse large B-cell lymphoma (LNH03-1B). Ann Oncol. 2013 Apr;24(4):1032-7. Epub 2012 Dec 12. link to original article PubMed

TBI, then auto HSCT

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Regimen

Study	Evidence	Comparator	Comparative Efficacy
Stiff et al. 2013 (SWOG S9704)	Phase III (E-esc)	R-CHOP x 8	Superior PFS

Preceding treatment

R-CHOP x 6

Autologous HSCT conditioning regimens Stem cells reinfused on day 0

References

SWOG S9704: Stiff PJ, Unger JM, Cook JR, Constine LS, Couban S, Stewart DA, Shea TC, Porcu P, Winter JN, Kahl BS, Miller TP, Tubbs RR, Marcellus D, Friedberg JW, Barton KP, Mills GM, LeBlanc M, Rimsza LM, Forman SJ, Fisher RI. Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. N Engl J Med. 2013 Oct 31;369(18):1681-90. link to original article link to PMC article PubMed
1. Subgroup analysis: Puvvada SD, Stiff PJ, Leblanc M, Cook JR, Couban S, Leonard JP, Kahl B, Marcellus D, Shea TC, Winter JN, Li H, Rimsza LM, Friedberg JW, Smith SM. Outcomes of MYC-associated lymphomas after R-CHOP with and without consolidative autologous stem cell transplant: subset analysis of randomized trial intergroup SWOG S9704. Br J Haematol. 2016 Sep;174(5):686-91. Epub 2016 Apr 13. link to original article link to PMC article PubMed

Z-BEAM, then auto HSCT

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Z-BEAM: Zevalin (Ibritumomab tiuxetan), BiCNU (Carmustine), Etoposide, Ara-C (Cytarabine), Melphalan

Regimen variant #1

Study	Evidence	Comparator	Comparative Efficacy
Shimoni et al. 2012 (SHEBA-07-4466-AN-CTIL)	Randomized Phase II (E-esc)	BEAM	Seems to have superior OS
Briones et al. 2013 (GELTAMO Z-BEAM LDCGB)	Phase II

Targeted therapy

Rituximab (Rituxan) 250 mg/m² IV once on day -14, given first

Radioconjugate therapy

Ibritumomab tiuxetan & Yttrium-90 (Zevalin) 0.4 mCi/kg (maximum dose of 32 mCi) IV once on day -14, given second

Chemotherapy

Carmustine (BCNU) 300 mg/m² IV once on day -6
Etoposide (Vepesid) 200 mg/m² IV once per day on days -5 to -2
Cytarabine (Ara-C) 200 mg/m² IV every 12 hours on days -5 to -2
Melphalan (Alkeran) 140 mg/m² IV once on day -1

Supportive therapy

Autologous stem cells re-infused on day 0
Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day +4 (Shimoni et al. 2012) or day +7 (GELTAMO Z-BEAM LDCGB) until engraftment
Valacyclovir (Valtrex) (dose not specified) for one month (Shimoni et al. 2012)
Acyclovir (Zovirax) (dose not specified) for one month (Briones et al. 2013)
Trimethoprim-Sulfamethoxazole (Bactrim DS) (dose/frequency not specified) for six months (3 months in GELTAMO Z-BEAM LDCGB)

One course

Regimen variant #2

Study	Evidence
Fruchart et al. 2014 (ZBEAM2)	Phase II

Preceding treatment

R-ACVBP or R-CHOP

Targeted therapy

Rituximab (Rituxan) 250 mg/m² IV once per day on days -21 & -14, given first on day -14

Radioconjugate therapy

Ibritumomab tiuxetan & Yttrium-90 (Zevalin) by the following laboratory-based criteria:
- Platelet count 150 x 10⁹/L or more: 0.4 mCi/kg (maximum dose of 32 mCi) IV once on day -14, given second
- Platelet count 100 up to 150 x 10⁹/L: 0.3 mCi/kg (maximum dose of 32 mCi) IV once on day -14, given second

Chemotherapy

Carmustine (BCNU) 300 mg/m² IV once on day -7
Etoposide (Vepesid) 100 mg/m² IV once per day on days -6 to -3
Cytarabine (Ara-C) 200 mg/m² IV every 12 hours on days -6 to -3
Melphalan (Alkeran) 140 mg/m² IV once on day -2

Supportive therapy

Autologous stem cells re-infused on day 0
"According to standard use"

One course

References

Shimoni A, Zwas ST, Oksman Y, Hardan I, Shem-Tov N, Yerushalmi R, Avigdor A, Ben-Bassat I, Nagler A. Yttrium-90-ibritumomab tiuxetan (Zevalin) combined with high-dose BEAM chemotherapy and autologous stem cell transplantation for chemo-refractory aggressive non-Hodgkin's lymphoma. Exp Hematol. 2007 Apr;35(4):534-40. link to original article PubMed
SHEBA-07-4466-AN-CTIL: Shimoni A, Avivi I, Rowe JM, Yeshurun M, Levi I, Or R, Patachenko P, Avigdor A, Zwas T, Nagler A. A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma. Cancer. 2012 Oct 1;118(19):4706-14. Epub 2012 Jan 17. link to original article contains verified protocol PubMed
GELTAMO Z-BEAM LDCGB: Briones J, Novelli S, García-Marco JA, Tomás JF, Bernal T, Grande C, Canales MA, Torres A, Moraleda JM, Panizo C, Jarque I, Palmero F, Hernández M, González-Barca E, López D, Caballero D. Autologous stem cell transplantation after conditioning with Yttrium-90 ibritumomab tiuxetan plus beam in refractory non-Hodgkin diffuse large B-cell lymphoma: results of a prospective, multicenter, phase II clinical trial. Haematologica. 2014 Mar;99(3):505-10. Epub 2013 Oct 25. link to original article contains verified protocol link to PMC article PubMed
ZBEAM2: Fruchart C, Tilly H, Morschhauser F, Ghesquières H, Bouteloup M, Fermé C, Van Den Neste E, Bordessoule D, Bouabdallah R, Delmer A, Casasnovas RO, Ysebaert L, Ciappuccini R, Briere J, Gisselbrecht C. Upfront consolidation combining yttrium-90 ibritumomab tiuxetan and high-dose therapy with stem cell transplantation in poor-risk patients with diffuse large B cell lymphoma. Biol Blood Marrow Transplant. 2014 Dec;20(12):1905-11. Epub 2014 Jul 26. link to original article contains verified protocol PubMed

Maintenance after upfront therapy

Lenalidomide monotherapy

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Regimen variant #1, 1 year

Study	Evidence	Comparator	Comparative Efficacy
Reddy et al. 2016 (VICC HEM 0835)	Randomized Phase II (E-de-esc)	Lenalidomide & Rituximab	Did not meet primary endpoint of RFS12

Preceding treatment

R-CHOP with or without radiation

Chemotherapy

Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21

28-day cycle for 12 cycles

Regimen variant #2, 2 years

Study	Evidence	Comparator	Comparative Efficacy
Thieblemont et al. 2017 (REMARC)	Phase III (E-esc)	Observation	Seems to have superior PFS

Preceding treatment

R-CHOP-21 or R-CHOP14

Chemotherapy

Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21

28-day cycle for up to 26 cycles (2 years)

References

VICC HEM 0835: Reddy NM, Greer JP, Morgan DS, Chen H, Park SI, Richards KL. A phase II randomized study of lenalidomide or lenalidomide and rituximab as maintenance therapy following standard chemotherapy for patients with high/high-intermediate risk diffuse large B-cell lymphoma. Leukemia. 2017 Jan;31(1):241-244. Epub 2016 Sep 22. link to original article link to PMC article contains verified protocol PubMed
REMARC: Thieblemont C, Tilly H, Gomes da Silva M, Casasnovas RO, Fruchart C, Morschhauser F, Haioun C, Lazarovici J, Grosicka A, Perrot A, Trotman J, Sebban C, Caballero D, Greil R, van Eygen K, Cohen AM, Gonzalez H, Bouabdallah R, Oberic L, Corront B, Choufi B, Lopez-Guillermo A, Catalano J, Van Hoof A, Briere J, Cabeçadas J, Salles G, Gaulard P, Bosly A, Coiffier B. Lenalidomide maintenance compared with placebo in responding elderly patients with diffuse large B-cell lymphoma treated with first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol. 2017 Aug 1;35(22):2473-2481. Epub 2017 Apr 20. link to original article contains verified protocol PubMed

Rituximab monotherapy

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Regimen variant #1

Study	Evidence	Comparator	Comparative Efficacy
Jaeger et al. 2015 (NHL13)	Phase III (E-esc)	Observation	Did not meet primary endpoint of EFS

Patients required to be in CR or CRu prior to enrollment. The protocol was amended after the first 69 patients enrolled to increase length of treatment from 1 to 2 years.

Preceding treatment

Rituximab (375 mg/m²) x 8 and 4 to 8 cycles of CHOP-like chemotherapy

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1

2-month cycle for 6 to 12 cycles (1 to 2 years)

Regimen variant #2

Study	Evidence	Comparator	Comparative Efficacy
Witzens-Harig et al. 2015 (HD2002)	Phase III (E-esc)	Observation	Superior OS in males

Preceding treatment

"Standard treatment" which was not further described in the paper, beyond that a majority of patient received R-CHOP (see Tables)

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1

3-month cycle for 8 cycles (2 years)

Regimen variant #3

Study	Evidence	Comparator	Comparative Efficacy
Haioun et al. 2009 (LNH 98-3)	Phase III (E-esc)	Observation	Might have superior EFS

Preceding treatment

CBVM, then auto HSCT

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once per day on days 1, 8, 15, 22

4-week course

Regimen variant #4

Study	Evidence	Comparator	Comparative Efficacy
Habermann et al. 2006 (ECOG E4494/CALGB 9793)	Phase III (E-esc)	Observation	Did not meet primary endpoint of FFS

Note: in ECOG E4494/CALGB 9793, rituximab maintenance had superior FFS in the group receiving CHOP upfront, which is no longer standard of care.

Preceding treatment

R-CHOP versus CHOP

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once per day on days 1, 8, 15, 22

6-month cycle for 4 cycles (2 years)

References

ECOG E4494/CALGB 9793: Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, Dakhil SR, Woda B, Fisher RI, Peterson BA, Horning SJ. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006 Jul 1;24(19):3121-7. Epub 2006 Jun 5. link to original article contains verified protocol PubMed
LNH 98-3: Haioun C, Mounier N, Emile JF, Ranta D, Coiffier B, Tilly H, Récher C, Fermé C, Gabarre J, Herbrecht R, Morchhauser F, Gisselbrecht C. Rituximab versus observation after high-dose consolidative first-line chemotherapy with autologous stem-cell transplantation in patients with poor-risk diffuse large B-cell lymphoma. Ann Oncol. 2009 Dec;20(12):1985-92. Epub 2009 Jun 30. link to original article contains verified protocol PubMed
NHL13: Jaeger U, Trneny M, Melzer H, Praxmarer M, Nawarawong W, Ben Yehuda D, Goldstein D, Mihaljevic B, Ilhan O, Ballova V, Hedenus M, Hsiao LT, Au WY, Burgstaller S, Weidinger G, Keil F, Dittrich C, Skrabs C, Klingler A, Chott A, Fridrik MA, Greil R. Rituximab maintenance for patients with aggressive B-cell lymphoma in first remission: results of the randomized NHL13 trial. Haematologica. 2015 Jul;100(7):955-63. Epub 2015 Apr 24. link to original article contains verified protocol link to PMC article PubMed
HD2002: Witzens-Harig M, Benner A, McClanahan F, Klemmer J, Brandt J, Brants E, Rieger M, Meissner J, Hensel M, Neben K, Dreger P, Lengfelder E, Schmidt-Wolf I, Krämer A, Ho AD. Rituximab maintenance improves survival in male patients with diffuse large B-cell lymphoma: results of the HD2002 prospective multicentre randomized phase III trial. Br J Haematol. 2015 Dec;171(5):710-9. Epub 2015 Oct 9. link to original article contains verified protocol PubMed

Relapsed or refractory, salvage therapy

O-DHAP

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O-DHAP: Ofatumumab, Dexamethasone, High-dose Ara-C (Cytarabine), Platinol (Cisplatin)

Regimen

Study	Evidence	Comparator	Comparative Efficacy
Matasar et al. 2013 (GSK 110927)	Phase II
van Imhoff et al. 2016 (ORCHARRD)	Phase III (E-switch-ic)	R-DHAP	Did not meet primary endpoint of PFS

Chemotherapy

Ofatumumab (Arzerra) as follows:
- Cycle 1: 1000 mg IV once per day on days 1 & 8
- Cycles 2 & 3: 1000 mg IV once on day 1
Dexamethasone (Decadron) 40 mg IV or PO once per day on days 1 to 4
Cytarabine (Ara-C) 2000 mg/m² IV every 12 hours on day 2 (total dose per cycle: 4000 mg/m²)
Cisplatin (Platinol) 100 mg/m² IV continuous infusion over 24 hours, started on day 1

Supportive medications

GSK 110927 recommended: Filgrastim (Neupogen) or Pegfilgrastim (Neulasta)

21-day cycle for 3 cycles

Subsequent treatment

GSK 110927, responders: Stem-cell mobilization and autologous hematopoietic stem cell transplant (regimen not specified)
ORCHARRD, responders: BEAM with autologous hematopoietic stem cell transplant except those in Japan who received LEED with autologous hematopoietic stem cell transplant

References

GSK 110927: Matasar MJ, Czuczman MS, Rodriguez MA, Fennessy M, Shea TC, Spitzer G, Lossos IS, Kharfan-Dabaja MA, Joyce R, Fayad L, Henkel K, Liao Q, Edvardsen K, Jewell RC, Fecteau D, Singh RP, Lisby S, Moskowitz CH. Ofatumumab in combination with ICE or DHAP chemotherapy in relapsed or refractory intermediate grade B-cell lymphoma. Blood. 2013 Jul 25;122(4):499-506. Epub 2013 May 21. link to original article contains verified protocol link to PMC article PubMed
ORCHARRD: van Imhoff GW, McMillan A, Matasar MJ, Radford J, Ardeshna KM, Kuliczkowski K, Kim W, Hong X, Goerloev JS, Davies A, Barrigón MD, Ogura M, Leppä S, Fennessy M, Liao Q, van der Holt B, Lisby S, Hagenbeek A. Ofatumumab versus rituximab salvage chemoimmunotherapy in relapsed or refractory diffuse large B-cell lymphoma: The ORCHARRD study. J Clin Oncol. 2017 Feb 10;35(5):544-51. Epub 2016 Dec 28. link to original article link to data supplement verified protocol in supplement PubMed

O-ICE

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O-ICE: Ofatumumab, Ifosfamide, Carboplatin, Etoposide

Regimen

Study	Evidence
Matasar et al. 2013 (GSK 110927)	Phase II

Note: Subsequent consolidation therapy was not specified.

Chemotherapy

Ofatumumab (Arzerra) as follows:
- Cycle 1: 1000 mg IV once per day on days 1 & 8
- Cycles 2 & 3: 1000 mg IV once on day 1
Ifosfamide (Ifex) 5000 mg/m² IV continuous infusion over 24 hours, started on day 2, mixed with Mesna (Mesnex)
Carboplatin (Paraplatin) AUC 5 (maximum dose of 800 mg) IV once on either day 1 or 2
- Carboplatin AUC calculated based on a 12-hour creatinine clearance
Etoposide (Vepesid) 100 mg/m² IV once per day on days 1 to 3

Supportive medications

Mesna (Mesnex) 5000 mg/m² IV continuous infusion over 24 hours, started on day 2, mixed with Ifosfamide (Ifex)
Recommended: Filgrastim (Neupogen) or Pegfilgrastim (Neulasta)

21-day cycle for 3 cycles

References

GSK 110927: Matasar MJ, Czuczman MS, Rodriguez MA, Fennessy M, Shea TC, Spitzer G, Lossos IS, Kharfan-Dabaja MA, Joyce R, Fayad L, Henkel K, Liao Q, Edvardsen K, Jewell RC, Fecteau D, Singh RP, Lisby S, Moskowitz CH. Ofatumumab in combination with ICE or DHAP chemotherapy in relapsed or refractory intermediate grade B-cell lymphoma. Blood. 2013 Jul 25;122(4):499-506. Epub 2013 May 21. link to original article contains verified protocol link to PMC article PubMed

R-DexaBEAM

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R-DexaBEAM: Rituximab, Dexamethasone, BiCNU (Carmustine), Etoposide, Ara-C (Cytarabine), Melphalan

Regimen

Study	Evidence
Kirschey et al. 2014 (Mz-135)	Phase II

Note: the dosing in the manuscript is different than below. The below are the correct doses as verified by the authors.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once per day on days 1 & 8
Dexamethasone (Decadron) 8 mg PO three times per day on days 1 to 10
Carmustine (BCNU) 60 mg/m² IV once on day 3
Etoposide (Vepesid) 75 mg/m² IV once per day on days 4 to 7
Cytarabine (Ara-C) 100 mg/m² IV twice per day on days 4 to 7
Melphalan (Alkeran) 20 mg/m² IV once on day 2

3- to 4-week cycle for 2 cycles

Subsequent treatment

R-BEAM with autologous hematopoietic stem cell transplant or R-TBI/Cy with autologous hematopoietic stem cell transplant

References

Mz-135: Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. link to original article contains verified protocol PubMed

R-DHAOx

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R-DHAOx: Rituximab, Dexamethasone, High-dose Ara-C (Cytarabine), Oxaliplatin
ROAD: Rituximab, Oxaliplatin, Ara-C (Cytarabine), Dexamethasone

Regimen

Study	Evidence	Efficacy
Witzig et al. 2017 (MCCRC MC0485)	Phase II	ORR: 71% (95% CI, 56–84)

Chemotherapy

Rituximab (Rituxan) as follows:
- Cycle 1 only: 375 mg/m² IV once per day on days 1, 8, 15, 22
Dexamethasone (Decadron) 40 mg IV or PO once per day on days 2 to 5
Cytarabine (Ara-C) 2000 mg/m² IV over 3 hours once per day on days 2 & 3
- Second dose to be given no sooner than 12 hours and no later than 24 hours after end of first dose
Oxaliplatin (Eloxatin) 130 mg/m² IV over 2 hours once on day 2

Supportive medications

Pegfilgrastim (Neulasta) 6 mg SC once on day 4

21-day cycles

Subsequent treatment

Most responders proceeded to high-dose chemotherapy with autologous hematopoietic stem cell transplant after 2 cycles, although this was not mandated in the protocol

References

MCCRC MC0485: Witzig TE, Johnston PB, LaPlant BR, Kurtin PJ, Pederson LD, Moore DF Jr, Nabbout NH, Nikcevich DA, Rowland KM, Grothey A. Long-term follow-up of chemoimmunotherapy with rituximab, oxaliplatin, cytosine arabinoside, dexamethasone (ROAD) in patients with relapsed CD20+ B-cell non-Hodgkin lymphoma: Results of a study of the Mayo Clinic Cancer Center Research Consortium (MCCRC) MC0485 now known as academic and community cancer research united (ACCRU). Am J Hematol. 2017 Oct;92(10):1004-1010. Epub 2017 Aug 17. link to original article contains verified protocol PubMed

R-DHAP

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R-DHAP: Rituximab, Dexamethasone, High-dose Ara-C (Cytarabine), Platinol (Cisplatin)

Regimen variant #1

Study	Evidence	Comparator	Comparative Efficacy
Gisselbrecht et al. 2010 (CORAL)	Phase III (E-switch-ic)	R-ICE	Did not meet primary endpoint of mobilization-adjusted response rate after 3 cycles
van Imhoff et al. 2016 (ORCHARRD)	Phase III (C)	O-DHAP	Did not meet primary endpoint of PFS

Note: CORAL makes reference to Velasquez et al. 1988 to describe this regimen, although this reference is for DHAP, not R-DHAP. The paper also contains the following regimen information:

Chemotherapy

Rituximab (Rituxan) as follows, given first:
- Cycle 1: 375 mg/m² IV once per day on days -1 & 1 (CORAL) or days 1 & 8 (ORCHARRD)
- Cycle 2: 375 mg/m² IV once on day 1
Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
Cytarabine (Ara-C) 2000 mg/m² IV over 3 hours every 12 hours on day 2 (total dose per cycle: 4000 mg/m²)
Cisplatin (Platinol) 100 mg/m² IV continuous infusion over 24 hours, started on day 1

Supportive medications

CORAL: G-CSF "depending on site policy, with R-DHAP, but always after the third cycle until the end of leukaphereses"

21-day cycle for 3 cycles

Subsequent treatment

CORAL, responders: BEAM with autologous hematopoietic stem cell transplant
ORCHARRD, responders: BEAM with autologous hematopoietic stem cell transplant except those in Japan who received LEED with autologous hematopoietic stem cell transplant

Regimen variant #2

Study	Evidence	Comparator	Comparative Efficacy
Crump et al. 2014 (NCIC-CTG LY.12)	Phase III (C)	R-GDP	Non-inferior RR after 2 cycles

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
Cytarabine (Ara-C) 2000 mg/m² IV over 3 hours every 12 hours on day 2 (total dose per cycle: 4000 mg/m²)
Cisplatin (Platinol) 100 mg/m² IV continuous infusion over 24 hours, started on day 1

21-day cycle for up to 3 cycles

Subsequent treatment

Responders: Stem-cell mobilization and high-dose chemotherapy with autologous hematopoietic stem cell transplant (regimen not specified)

Regimen variant #3

Study	Evidence
Mey et al. 2006	Phase II

The doses here were used after a mid-protocol amendment pertaining to the first cycle.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Dexamethasone (Decadron) as follows:
- Cycle 1: 40 mg PO once per day on days 3 to 5
- Cycles 2 to 4: 40 mg PO once per day on days 3 to 6
Cytarabine (Ara-C) as follows:
- Cycle 1 as follows:
  - Younger than 60 years: 1000 mg/m² IV over 2 hours every 12 hours on day 4 (total dose per cycle: 2000 mg/m²)
  - Older than 60 years: 500 mg/m² IV over 2 hours every 12 hours on day 4 (total dose per cycle: 1000 mg/m²)
- Cycles 2 to 4 as follows:
  - Younger than 60 years: 2000 mg/m² IV over 2 hours every 12 hours on day 4 (total dose per cycle: 4000 mg/m²)
  - Older than 60 years: 1000 mg/m² IV over 2 hours every 12 hours on day 4 (total dose per cycle: 2000 mg/m²)
Cisplatin (Platinol) as follows:
- Cycle 1: 25 mg/m²/day IV continuous infusion over 72 hours, started on day 3 (total dose: 75 mg/m²)
- Cycles 2 to 4: 25 mg/m²/day IV continuous infusion over 96 hours, started on day 3 (total dose per cycle: 100 mg/m²)

21-day cycle for up to 4 cycles

Subsequent treatment

Patients with at least PR were allowed to undergo high-dose chemotherapy with autologous stem-cell transplant (regimen not specified)

References

Mey UJ, Orlopp KS, Flieger D, Strehl JW, Ho AD, Hensel M, Bopp C, Gorschlüter M, Wilhelm M, Birkmann J, Kaiser U, Neubauer A, Florschütz A, Rabe C, Hahn C, Glasmacher AG, Schmidt-Wolf IG. Dexamethasone, high-dose cytarabine, and cisplatin in combination with rituximab as salvage treatment for patients with relapsed or refractory aggressive non-Hodgkin's lymphoma. Cancer Invest. 2006 Oct;24(6):593-600. link to original article contains verified protocol PubMed
CORAL: Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Brière J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. Epub 2010 Jul 26. Erratum in: J Clin Oncol. 2012 May 20;30(15):1896. link to original article contains verified protocol link to PMC article PubMed
NCIC-CTG LY.12: Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. link to original article contains verified protocol PubMed
ORCHARRD: van Imhoff GW, McMillan A, Matasar MJ, Radford J, Ardeshna KM, Kuliczkowski K, Kim W, Hong X, Goerloev JS, Davies A, Barrigón MD, Ogura M, Leppä S, Fennessy M, Liao Q, van der Holt B, Lisby S, Hagenbeek A. Ofatumumab versus rituximab salvage chemoimmunotherapy in relapsed or refractory diffuse large B-cell lymphoma: the ORCHARRD study. J Clin Oncol. 2017 Feb 10;35(5):544-51. Epub 2016 Dec 28. link to original article link to data supplement verified protocol in supplement PubMed

R-DHAP/R-VIM

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R-DHAP/R-VIM: Rituximab, Dexamethasone, High-dose Ara-C (Cytarabine), Platinol (Cisplatin) alternating with Rituximab, VP-16 (Etoposide), Ifosfamide, Methotrexate

Protocol

Study	Evidence	Comparator	Comparative Efficacy
Vellenga et al. 2008 (HOVON-44)	Phase III (E-esc)	DHAP/VIM	Superior PFS

Note: per the paper, "in case patients were non-responsive to R-DHAP but responsive to R-VIM, it was allowed to repeat the R-VIM regimen as the third cycle of reinduction chemotherapy." No statement is made as to whether Mesna is used in the VIM protocol.

Chemotherapy, R-DHAP portion

Rituximab (Rituxan) 375 mg/m² IV once on day 5
Dexamethasone (Decadron) 40 mg IV or PO once per day on days 1 to 4
Cytarabine (Ara-C) 2000 mg/m² IV over 3 hours every 12 hours on day 2 (total dose per cycle: 4000 mg/m²)
Cisplatin (Platinol) 100 mg/m² IV continuous infusion over 24 hours, started on day 1

28-day cycle for 2 cycles, with VIM interposed

Chemotherapy, R-VIM portion

Rituximab (Rituxan) 375 mg/m² IV once on day 6
Etoposide (Vepesid) 90 mg/m² IV once per day on days 1, 3, 5
Ifosfamide (Ifex) 1200 mg/m² IV once per day on days 1 to 5
Methotrexate (MTX) 30 mg/m² IV once per day on days 1 & 5

28-day cycle for 1 cycle, given in-between R-DHAP cycles

Subsequent treatment

Responders: Stem-cell mobilization, then BEAM with autologous hematopoietic stem cell transplant

References

Vellenga E, van Putten WL, van 't Veer MB, Zijlstra JM, Fibbe WE, van Oers MH, Verdonck LF, Wijermans PW, van Imhoff GW, Lugtenburg PJ, Huijgens PC. Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20+ NHL: a prospective randomized HOVON trial. Blood. 2008 Jan 15;111(2):537-43. link to original article contains verified protocol PubMed

R-EPOCH

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R-EPOCH: Rituximab, Etoposide, Prednisone, Oncovin (Vincristine), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin)

Regimen

Study	Evidence
Jermann et al. 2004	Phase II

Note: this is not the dose-adjusted R-EPOCH regimen

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Etoposide (Vepesid) 65 mg/m²/day IV continuous infusion over 72 hours, started on day 2 (total dose per cycle: 195 mg/m²)
Prednisone (Sterapred) 60 mg/m²/day PO on days 1 to 14
Vincristine (Oncovin) 0.5 mg/m²/day IV continuous infusion over 72 hours, started on day 2 (total dose per cycle: 1.5 mg/m²)
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 5
Doxorubicin (Adriamycin) 15 mg/m²/day IV continuous infusion over 72 hours, started on day 2 (total dose per cycle: 45 mg/m²)

21-day cycle for 4 to 6 cycles

Subsequent treatment

Patients younger than 60 who achieved at least PR: High-dose chemotherapy with autologous hematopoietic stem-cell transplantation (regimen not specified)

References

Jermann M, Jost LM, Taverna Ch, Jacky E, Honegger HP, Betticher DC, Egli F, Kroner T, Stahel RA. Rituximab-EPOCH, an effective salvage therapy for relapsed, refractory or transformed B-cell lymphomas: results of a phase II study. Ann Oncol. 2004 Mar;15(3):511-6. link to original article contains verified protocol PubMed

R-ESHAP

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R-ESHAP: Rituximab, Etoposide, Solumedrol (Methylprednisolone) High-dose Ara-C (Cytarabine), Platinol (Cisplatin)

Regimen

Study	Evidence	Comparator	Comparative Efficacy
Martín et al. 2008	Retrospective
Avilés et al. 2010	Phase III (E-esc)	ESHAP	Did not meet efficacy endpoints

Regimen details are based on ESHAP paper from 1994. Per retrospective review (Martin et al. 2008), 90% of patients given R-ESHAP received rituximab on day 1, 10% on day 5.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1 (or day 5)
Etoposide (Vepesid) 40 mg/m² IV over 60 minutes once per day on days 1 to 4
Methylprednisolone (Solumedrol) 250 to 500 mg IV over 15 minutes once per day on days 1 to 5
- In Martín et al. 2008, could either be given on days 1 to 4 or days 1 to 5, with patients receiving total doses of anywhere from 1000 mg per cycle to 2500 mg per cycle
Cytarabine (Ara-C) 2000 mg/m² IV over 2 hours once on day 5
Cisplatin (Platinol) 25 mg/m²/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 100 mg/m²)

Supportive medications

At least 1 liter normal saline with 25 to 50 g Mannitol once per day throughout chemotherapy
Metoclopramide (Reglan) 0.5 to 1 mg/kg (route not specified) "given regularly"

21- to 28-day cycles for 6 to 8 cycles ("after recovery of the toxic effects")

References

Retrospective: Martín A, Conde E, Arnan M, Canales MA, Deben G, Sancho JM, Andreu R, Salar A, García-Sanchez P, Vázquez L, Nistal S, Requena MJ, Donato EM, González JA, León A, Ruiz C, Grande C, González-Barca E, Caballero MD; Grupo Español de Linfomas/Trasplante Autólogo de Médula Osea (GEL/TAMO Cooperative Group). R-ESHAP as salvage therapy for patients with relapsed or refractory diffuse large B-cell lymphoma: the influence of prior exposure to rituximab on outcome. A GEL/TAMO study. Haematologica. 2008 Dec;93(12):1829-36. Epub 2008 Oct 22. link to original article contains verified protocol PubMed
Avilés A, Neri N, Huerta-Guzmán J, de Jesús Nambo M. ESHAP versus rituximab-ESHAP in frail patients with refractory diffuse large B-cell lymphoma. Clin Lymphoma Myeloma Leuk. 2010 Apr;10(2):125-8. link to original article PubMed

R-GDP

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R-GDP: Rituximab, Gemcitabine, Dexamethasone, Platinol (Cisplatin)

Regimen variant #1, 1 day of cisplatin/cycle

Study	Evidence	Comparator	Comparative Efficacy
Crump et al. 2014 (NCIC-CTG LY.12)	Phase III (E-switch-ic)	R-DHAP	Non-inferior RR after 2 cycles

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Gemcitabine (Gemzar) 1000 mg/m² IV once per day on days 1 & 8
Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
Cisplatin (Platinol) 75 mg/m² IV once on day 1

21-day cycle for up to 3 cycles

Subsequent treatment

Responders: Stem-cell mobilization and high-dose chemotherapy with autologous hematopoietic stem cell transplant (regimen not specified)

Regimen variant #2, 3 days of cisplatin/cycle

Study	Evidence
Hou et al. 2012	Non-randomized

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Gemcitabine (Gemzar) 1000 mg/m² IV once per day on days 1 & 8
Dexamethasone (Decadron) 40 mg IV once per day on days 1 to 4
Cisplatin (Platinol) 25 mg/m² IV once per day on days 1 to 3

21-day cycle for up to 6 cycles

References

Hou Y, Wang HQ, Ba Y. Rituximab, gemcitabine, cisplatin, and dexamethasone in patients with refractory or relapsed aggressive B-cell lymphoma. Med Oncol. 2012 Dec;29(4):2409-16. Epub 2012 Apr 3. link to original article PubMed
NCIC-CTG LY.12: Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. link to original article contains verified protocol PubMed

R-ICE

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R-ICE: Rituximab, Ifosfamide, Carboplatin, Etoposide
ICE-R: Ifosfamide, Carboplatin, Etoposide, Rituximab

Regimen variant #1

Study	Evidence	Comparator	Comparative Efficacy
Gisselbrecht et al. 2010 (CORAL)	Phase III (E-switch-ic)	R-DHAP	Did not meet primary endpoint of mobilization-adjusted response rate after 3 cycles
Fayad et al. 2015 (SG040-0005)	Randomized Phase IIb (C)	R-ICE + Dacetuzumab	Did not meet primary endpoint of CR rate

Note: Gisselbrecht et al. 2010 refers to the non-randomized regimen described in variant #3 below, although it has slightly different day numbering. Doses are the same.

Chemotherapy

Rituximab (Rituxan) as follows (given first before other chemotherapy):
- Cycle 1: 375 mg/m² IV once per day on days -1 & 1
- Cycles 2 & 3: 375 mg/m² IV once on day 1
Ifosfamide (Ifex) 5000 mg/m² IV continuous infusion over 24 hours, started on day 2
Carboplatin (Paraplatin) AUC 5 (maximum dose of 800 mg) IV once on day 2
Etoposide (Vepesid) 100 mg/m² IV once per day on days 1 to 3

Supportive medications

Mesna (Mesnex) given with Ifosfamide (Ifex) (dose & schedule not specified)
" Granulocyte colony-stimulating factor was administered after R-ICE"

21-day cycle for 3 cycles

Subsequent treatment

CORAL with complete or partial response: BEAM with autologous hematopoietic stem cell transplant

Regimen variant #2

Study	Evidence	Efficacy
Guo et al. 2014	Phase II	ORR: 78%

Note: original article is in Chinese; this information is from the English abstract.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Ifosfamide (Ifex) 1600 mg/m² IV once per day on days 2 to 4
Carboplatin (Paraplatin) AUC 5 (maximum dose of 800 mg) IV once on day 3
Etoposide (Vepesid) 100 mg/m² IV once per day on days 2 to 4

3 cycles; duration of cycles not specified in the abstract

Regimen variant #3

Study	Evidence	Efficacy
Zelenetz et al. 2003	Phase II	ORR: 81% (*)
Kewalramani et al. 2004	Phase II	ORR: 78% (*)

Third cycle intended to be followed by peripheral blood hematopoietic stem cell collection. ORR reported in Zelenetz et al. 2003 is for the subset of DLBCL patients who received R-ICE; it is unclear if these patients were exposed to rituximab previously. None of the patients in Kewalaramani et al. 2004 had previously received rituximab.

Chemotherapy

Rituximab (Rituxan) as follows:
- Cycle 1: 375 mg/m² IV once per day on days -2 & 1
- Cycles 2 & 3: 375 mg/m² IV once on day 1
Ifosfamide (Ifex) 5000 mg/m² IV continuous infusion over 24 hours, started on day 4, mixed with Mesna (Mesnex)
Carboplatin (Paraplatin) AUC 5 (maximum dose of 800 mg) IV bolus once on day 4
- Carboplatin AUC calculated based on a 12-hour creatinine clearance
Etoposide (Vepesid) 100 mg/m² IV bolus once per day on days 3 to 5

Supportive medications

(as described by Kewalramani et al. 2004):
Mesna (Mesnex) 5000 mg/m² IV continuous infusion over 24 hours, started on day 4, mixed with Ifosfamide (Ifex)
Acetaminophen (Tylenol) 650 mg PO once as premedication for Rituximab (Rituxan)
Diphenhydramine (Benadryl) 50 mg IV once as premedication for Rituximab (Rituxan)
Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 7 to 14 (10 mcg/kg with cycle 3, given until collection of peripheral blood hematopoietic stem cells)

14-day cycle for 3 cycles

References

Zelenetz AD, Hamlin P, Kewalramani T, Yahalom J, Nimer S, Moskowitz CH. Ifosfamide, carboplatin, etoposide (ICE)-based second-line chemotherapy for the management of relapsed and refractory aggressive non-Hodgkin's lymphoma. Ann Oncol. 2003;14 Suppl 1:i5-10. link to original article contains verified protocol PubMed
Kewalramani T, Zelenetz AD, Nimer SD, Portlock C, Straus D, Noy A, O'Connor O, Filippa DA, Teruya-Feldstein J, Gencarelli A, Qin J, Waxman A, Yahalom J, Moskowitz CH. Rituximab and ICE as second-line therapy before autologous stem cell transplantation for relapsed or primary refractory diffuse large B-cell lymphoma. Blood. 2004 May 15;103(10):3684-8. Epub 2004 Jan 22. link to original article contains protocol PubMed
Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Brière J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. Epub 2010 Jul 26. Erratum in: J Clin Oncol. 2012 May 20;30(15):1896. link to original article contains verified protocol link to PMC article PubMed
Guo Y, Chen Y, Hong X, Yu L, Ma J, Shi Y, Liu T, Jiang W, Zhu J, Jin J, Zou P, Wu D, Shen Z. [A phase II multicenter study to investigate R-ICE as a salvage therapy for relapsed diffuse large B-cell lymphoma]. Zhonghua Xue Ye Xue Za Zhi. 2014 Apr;35(4):314-7. Chinese. link to original article contains protocol PubMed
SG040-0005: Fayad L, Ansell SM, Advani R, Coiffier B, Stuart R, Bartlett NL, Forero-Torres A, Kuliczkowski K, Belada D, Ng E, Drachman JG. Dacetuzumab plus rituximab, ifosfamide, carboplatin and etoposide as salvage therapy for patients with diffuse large B-cell lymphoma relapsing after rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone: a randomized, double-blind, placebo-controlled phase 2b trial. Leuk Lymphoma. 2015;56(9):2569-78. Epub 2015 Feb 26. link to original article PubMed

RICER

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RICER: Rituximab, Ifosfamide, Carboplatin, Etoposide, Revlimid (Lenalidomide)

Regimen

Study	Evidence
Feldman et al. 2014 (RV-DLBCL-PI-0463)	Phase II

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Ifosfamide (Ifex) 5000 mg/m² IV continuous infusion over 24 hours, started on day 2, mixed with Mesna (Mesnex)
Carboplatin (Paraplatin) AUC 5 (maximum dose of 800 mg) IV once on day 2
Etoposide (Vepesid) 100 mg/m² IV bolus once per day on days 2 to 4
Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 7

Supportive medications

Mesna (Mesnex) 5000 mg/m² IV continuous infusion over 24 hours, started on day 2, mixed with Ifosfamide (Ifex)
Aspirin 81 mg PO once per day from day 1 until platelets less than 50 × 10⁹/L
Low dose LMWH for patients intolerant of Aspirin
" Granulocyte colony-stimulating factor was administered after R-ICE"

14-day cycle for 2 cycles

Subsequent treatment

Responders received a 3rd cycle with hematopoietic stem cell collection 10 to 14 days afterwards, then BEAM with autologous hematopoietic stem cell transplant (details not described)

References

RV-DLBCL-PI-0463: Feldman T, Mato AR, Chow KF, Protomastro EA, Yannotti KM, Bhattacharyya P, Yang X, Donato ML, Rowley SD, Carini C, Valentinetti M, Smith J, Gadaleta G, Bejot C, Stives S, Timberg M, Kdiry S, Pecora AL, Beaven AW, Goy A. Addition of lenalidomide to rituximab, ifosfamide, carboplatin, etoposide (RICER) in first-relapse/primary refractory diffuse large B-cell lymphoma. Br J Haematol. 2014 Jul;166(1):77-83. Epub 2014 Mar 25. link to original article contains verified protocol link to PMC article PubMed

R-IFE

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R-IFE: Rituximab, IFosfamide, Etoposide

Regimen

Study	Evidence
Pardal et al. 2014 (GELTAMO-2006)	Phase II

These were patients with PET-positive disease at interim assessment.

Preceding treatment

R-MegaCHOP x 3

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Ifosfamide (Ifex) 3333 mg/m²/day IV continuous infusion over 72 hours, started on day 1 (total dose per cycle: 10,000 mg/m²)
Etoposide (Vepesid) 150 mg/m² IV over 12 hours once per day on days 1 to 3

Supportive medications

Mesna (Mesnex) given after R-IFE; details not supplied in manuscript
Pegfilgrastim (Neulasta) given after each cycle

2 cycles (duration not specified)

Subsequent treatment

Responders: BEAM with autologous hematopoietic stem cell transplant

References

GELTAMO-2006: Pardal E, Coronado M, Martín A, Grande C, Marín-Niebla A, Panizo C, Bello JL, Conde E, Hernández MT, Arranz R, Bargay J, González-Barca E, Pérez-Ceballos E, Montes-Moreno S, Caballero MD. Intensification treatment based on early FDG-PET in patients with high-risk diffuse large B-cell lymphoma: a phase II GELTAMO trial. Br J Haematol. 2014 Nov;167(3):327-36. Epub 2014 Jul 28. link to original article contains verified protocol PubMed

R-NIMP

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R-NIMP: Rituximab, Navelbine (Vinorelbine), Ifosfamide, Mitoxantrone, Prednisone

Regimen

Study	Evidence	Efficacy
Gyan et al. 2013	Phase II	68% (95%CI: 53–79)

BSA was capped at 2 for all dose calculations.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Vinorelbine (Navelbine) 25 mg/m² IV once per day on days 1 & 15
Ifosfamide (Ifex) 1000 mg/m²/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 5000 mg/m²)
Mitoxantrone (Novantrone) 10 mg/m² IV once on day 1
Prednisone (Sterapred) 1 mg/kg (route not specified) once per day on days 1 to 5

Supportive medications

Mesna (Mesnex) given with Ifosfamide (Ifex) "at the same dose"; schedule not specified in the paper
Recommended: Pegfilgrastim (Neulasta) 6 mg SC once on day 7
Recommended: Epoietin alpha support for hemoglobin less than 10 g/dL

28-day cycle for 3 cycles

Subsequent treatment

Responders were recommended to undergo 3 additional cycles of R-NIMP (if transplant ineligible) or high-dose chemotherapy with autologous hematopoietic stem cell transplant (regimen not specified).

References

Gyan E, Damotte D, Courby S, Sénécal D, Quittet P, Schmidt-Tanguy A, Banos A, Le Gouill S, Lamy T, Fontan J, Maisonneuve H, Alexis M, Dreyfus F, Tournilhac O, Laribi K, Solal-Céligny P, Arakelyan N, Cartron G, Gressin R; GOELAMS Group. High response rate and acceptable toxicity of a combination of rituximab, vinorelbine, ifosfamide, mitoxantrone and prednisone for the treatment of diffuse large B-cell lymphoma in first relapse: results of the R-NIMP GOELAMS study. Br J Haematol. 2013 Jul;162(2):240-9. Epub 2013 May 21. link to original article contains verified protocol PubMed

Consolidation after salvage therapy

BEAC, then auto HSCT

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BEAC: Rituximab, BiCNU (Carmustine), Etoposide, Ara-C (Cytarabine), Cyclophosphamide

Regimen

Study	Evidence	Comparator	Comparative Efficacy
Philip et al. 1991 (Parma)	Prospective pilot
Philip et al. 1995 (PARMA)	Phase III (E-esc)	DHAP x 4	Seems to have superior OS

Preceding treatment

DHAP x 2; radiation was also given to sites of bulky disease (>5cm) Autologous HSCT conditioning regimens

References

Philip T, Chauvin F, Armitage J, Bron D, Hagenbeek A, Biron P, Spitzer G, Velasquez W, Weisenburger DD, Fernandez-Ranada J, Somers R, Rizzoli V, Harousseau JL, Sotto JJ, Cahn JY, Guilhot F, Biggs J, Sonneveld P, Misset JL, Manna A, Jagannath S, Guglielmi C, Chevreau C, Delmer A, Santini G, Coiffier B. Parma international protocol: pilot study of DHAP followed by involved-field radiotherapy and BEAC with autologous bone marrow transplantation. Blood. 1991 Apr 1;77(7):1587-92. link to original article contains verified protocol PubMed
PARMA: Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, Coiffier B, Biron P, Mandelli F, Chauvin F. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med. 1995 Dec 7;333(23):1540-5. link to original article PubMed

BEAM, then allo HSCT

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BEAM: BiCNU (Carmustine), Etoposide, Ara-C (Cytarabine), Melphalan

Regimen

Study	Evidence
Przepiorka et al. 1999	Phase II

Chemotherapy

Carmustine (BCNU) 300 mg/m² IV once on day -6
Etoposide (Vepesid) 200 mg/m² IV twice per day on days -5 to -2
Cytarabine (Ara-C) 200 mg/m² IV twice per day on days -5 to -2
Melphalan (Alkeran) 140 mg/m² IV once on day -1

Immunotherapy

Allogeneic stem cells transfused on day 0

GVHD prophylaxis

Supportive therapy

"Prophylactic antibiotics"
Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day +7 and continued until engraftment

One course

Immunotherapy

Allogeneic stem cells

Stem cells transfused on day 0

References

Przepiorka D, van Besien K, Khouri I, Hagemeister F, Samuels B, Folloder J, Ueno NT, Molldrem J, Mehra R, Körbling M, Giralt S, Gajewski J, Donato M, Cleary K, Claxton D, Braunschweig I, Andersson B, Anderlini P, Champlin R. Carmustine, etoposide, cytarabine and melphalan as a preparative regimen for allogeneic transplantation for high-risk malignant lymphoma. Ann Oncol. 1999 May;10(5):527-32. link to original article contains protocol PubMed

BEAM, then auto HSCT

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BEAM: Rituximab, BiCNU (Carmustine), Etoposide, Ara-C (Cytarabine), Melphalan

Regimen variant #1

Study	Evidence	Comparator	Comparative Efficacy
Shimoni et al. 2012 (SHEBA-07-4466-AN-CTIL)	Randomized Phase II (C)	Z-BEAM	Seems to have inferior OS
Pardal et al. 2014 (GELTAMO-2006)	Phase II
van Imhoff et al. 2016 (ORCHARRD)	Non-randomized portion of RCT

Preceding treatment

GELTAMO-2006: R-MegaCHOP x 3, then R-IFE x 2
ORCHARRD: O-DHAP x 3 versus R-DHAP x 3

Chemotherapy

Carmustine (BCNU) 300 mg/m² IV once on day -6
Etoposide (Vepesid) 200 mg/m² IV once per day on days -5 to -2
Cytarabine (Ara-C) 200 mg/m² IV every 12 hours on days -5 to -2 (total dose: 1600 mg/m²)
Melphalan (Alkeran) 140 mg/m² IV once on day -1

Supportive therapy

Autologous stem cells re-infused on day 0
Variously described:
Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day +4 "until engraftment"
Valacyclovir (Valtrex) (dose not specified) for one month
Trimethoprim-Sulfamethoxazole (Bactrim DS) (dose/frequency not specified) for six months

One course

Stem cells reinfused on day 0

Regimen variant #2

Study	Evidence
Vellenga et al. 2008 (HOVON-44)	Non-randomized portion of RCT
Gisselbrecht et al. 2010 (CORAL)	Non-randomized portion of RCT

Preceding treatment

HOVON-44: DHAP/VIM versus R-DHAP/R-VIM
CORAL: R-ICE x 3 versus R-DHAP x 3

Chemotherapy

Carmustine (BCNU) 300 mg/m² IV once on day -6
Etoposide (Vepesid) 200 mg/m² IV once per day on days -5 to -2
Cytarabine (Ara-C) 200 mg/m² IV once per day on days -5 to -2
Melphalan (Alkeran) 140 mg/m² IV once on day -1

Supportive therapy

Autologous stem cells re-infused on day 0

One course

Stem cells reinfused on day 0

Subsequent treatment

CORAL: Rituximab maintenance versus observation

Regimen variant #3, 300/100q12/200/140

Study	Evidence
Philip et al. 1987	Non-randomized

Chemotherapy

Carmustine (BCNU) 300 mg/m² IV once on day 1
Etoposide (Vepesid) 100 mg/m² IV over 60 minutes every 12 hours on days 2 to 5 (total dose: 800 mg/m²)
Cytarabine (Ara-C) 200 mg/m² IV once per day on days 2 to 5
Melphalan (Alkeran) 140 mg/m² IV over 5 minutes once on day 6

Supportive therapy

Autologous stem cells re-infused on unspecified day

One course

References

Philip T, Armitage JO, Spitzer G, Chauvin F, Jagannath S, Cahn JY, Colombat P, Goldstone AH, Gorin NC, Flesh M, Laporte JP, Maraninchi D, Pico J, Bosly A, Anderson C, Schots R, Biron P, Cabanillas F, Dicke K. High-dose therapy and autologous bone marrow transplantation after failure of conventional chemotherapy in adults with intermediate-grade or high-grade non-Hodgkin's lymphoma. N Engl J Med. 1987 Jun 11;316(24):1493-8. link to original article contains verified protocol PubMed
HOVON-44: Vellenga E, van Putten WL, van 't Veer MB, Zijlstra JM, Fibbe WE, van Oers MH, Verdonck LF, Wijermans PW, van Imhoff GW, Lugtenburg PJ, Huijgens PC. Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20+ NHL: a prospective randomized HOVON trial. Blood. 2008 Jan 15;111(2):537-43. link to original article contains verified protocol PubMed
CORAL: Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Brière J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. Epub 2010 Jul 26. Erratum in: J Clin Oncol. 2012 May 20;30(15):1896. link to original article contains verified protocol link to PMC article PubMed
SHEBA-07-4466-AN-CTIL: Shimoni A, Avivi I, Rowe JM, Yeshurun M, Levi I, Or R, Patachenko P, Avigdor A, Zwas T, Nagler A. A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma. Cancer. 2012 Oct 1;118(19):4706-14. Epub 2012 Jan 17. link to original article contains verified protocol PubMed
GELTAMO-2006: Pardal E, Coronado M, Martín A, Grande C, Marín-Niebla A, Panizo C, Bello JL, Conde E, Hernández MT, Arranz R, Bargay J, González-Barca E, Pérez-Ceballos E, Montes-Moreno S, Caballero MD. Intensification treatment based on early FDG-PET in patients with high-risk diffuse large B-cell lymphoma: a phase II GELTAMO trial. Br J Haematol. 2014 Nov;167(3):327-36. Epub 2014 Jul 28. link to original article contains verified protocol PubMed
ORCHARRD: van Imhoff GW, McMillan A, Matasar MJ, Radford J, Ardeshna KM, Kuliczkowski K, Kim W, Hong X, Goerloev JS, Davies A, Barrigón MD, Ogura M, Leppä S, Fennessy M, Liao Q, van der Holt B, Lisby S, Hagenbeek A. Ofatumumab versus rituximab salvage chemoimmunotherapy in relapsed or refractory diffuse large B-cell lymphoma: the ORCHARRD study. J Clin Oncol. 2017 Feb 10;35(5):544-51. Epub 2016 Dec 28. link to original article link to data supplement verified protocol in supplement PubMed

BeEAM, then auto HSCT

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BeEAM: Bendamustine, Etoposide, Ara-C (Cytarabine), Melphalan

Regimen

Study	Evidence
Visani et al. 2011	Phase I/II, <20 pts in this subgroup

Chemotherapy

Bendamustine 200 mg/m² IV once per day on days -7 & -6
Etoposide (Vepesid) 200 mg/m² IV once per day on days -5 to -2
Cytarabine (Ara-C) 400 mg/m² IV once per day on days -5 to -2
Melphalan (Alkeran) 140 mg/m² IV once on day -1

Supportive therapy

Autologous stem cells re-infused on day 0

One course

References

Visani G, Malerba L, Stefani PM, Capria S, Galieni P, Gaudio F, Specchia G, Meloni G, Gherlinzoni F, Giardini C, Falcioni S, Cuberli F, Gobbi M, Sarina B, Santoro A, Ferrara F, Rocchi M, Ocio EM, Caballero MD, Isidori A. BeEAM (bendamustine, etoposide, cytarabine, melphalan) before autologous stem cell transplantation is safe and effective for resistant/relapsed lymphoma patients. Blood. 2011 Sep 22;118(12):3419-25. Epub 2011 Aug 3. link to original article contains verified protocol PubMed

CBV, then auto HSCT

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CBV: Cyclophosphamide, BiCNU (Carmustine), VP-16 (Etoposide)

Regimen

Study	Evidence
Stiff et al. 1998	Phase II

Chemotherapy

Cyclophosphamide (Cytoxan) 100 mg/kg IV over 2 hours once on day -2
Carmustine (BCNU) 15 mg/kg (maximum dose of 550 mg/m²) IV over 60 minutes once on day -6
Etoposide (Vepesid) 60 mg/kg IV over 4 hours once on day -4

Supportive therapy

Autologous stem cells re-infused on day 0
Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day +4, to continue until ANC greater than 5000/μL once or greater than 1500/μL twice
Levofloxacin (Levaquin) 500 mg PO once per day, starting on day +2, to continue until ANC at least 500/μL
Fluconazole (Diflucan) 200 mg PO once per day, starting on day +1, to continue until ANC at least 500/μL
Acyclovir (Zovirax) 200 mg PO three times per day, starting on day -2, to continue until 1 year after HSCT
Trimethoprim-Sulfamethoxazole (Bactrim DS) 160/800 mg PO twice per day on Saturday and Sunday, to continue until 3 months after HSCT

Additional considerations

If any patient appeared to be experiencing carmustine-induced pneumonitis:

Prednisone (Sterapred) 0.5 mg/kg PO twice per day x 2 weeks, then tapered over 4 weeks

One course

References

Stiff PJ, Dahlberg S, Forman SJ, McCall AR, Horning SJ, Nademanee AP, Blume KG, LeBlanc M, Fisher RI. Autologous bone marrow transplantation for patients with relapsed or refractory diffuse aggressive non-Hodgkin's lymphoma: value of augmented preparative regimens--a Southwest Oncology Group trial. J Clin Oncol. 1998 Jan;16(1):48-55. link to original article contains verified protocol PubMed

Cyclophosphamide & TBI, then auto HSCT

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Cy/TBI: Cyclophosphamide & Total Body Irradiation

Regimen

Study	Evidence
Phillips et al. 1984	Non-randomized

Chemotherapy

Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 & -2

Radiotherapy

Total body irradiation (TBI) 1200 cGy in fractions on days –6 to –4 (pulmonary dosage was limited to 800 cGy)

Supportive therapy

Autologous stem cells re-infused on day 0

One course

References

Phillips GL, Herzig RH, Lazarus HM, Fay JW, Wolff SN, Mill WB, Lin H, Thomas PR, Glasgow GP, Shina DC, Herzig GP. Treatment of resistant malignant lymphoma with cyclophosphamide, total body irradiation, and transplantation of cryopreserved autologous marrow. N Engl J Med. 1984 Jun 14;310(24):1557-61. link to original article PubMed

FEAM, then auto HSCT

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FEAM: Fotemustine, Etoposide, Ara-C (Cytarabine), Melphalan

Regimen

Study	Evidence
Musso et al. 2009	Phase II

Chemotherapy

Fotemustine (Muphoran) 150 mg/m² IV once per day on days -7 & -6 (total dose: 300 mg/m²)
Etoposide (Vepesid) 200 mg/m² IV once per day on days -5 to -2 (total dose: 800 mg/m²)
Cytarabine (Ara-C) 400 mg/m² IV once per day on days -5 to -2 (total dose: 1600 mg/m²)
Melphalan (Alkeran) 140 mg/m² IV once on day -1

Supportive therapy

Autologous stem cells re-infused on day 0

One course

References

Musso M, Scalone R, Marcacci G, Lanza F, Di Renzo N, Cascavilla N, Di Bartolomeo P, Crescimanno A, Perrone T, Pinto A. Fotemustine plus etoposide, cytarabine and melphalan (FEAM) as a new conditioning regimen for lymphoma patients undergoing auto-SCT: a multicenter feasibility study. Bone Marrow Transplant. 2010 Jul;45(7):1147-53. Epub 2009 Nov 9. link to original article PubMed

FluBuCy, then allo HSCT

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FluBuCy: Fludarabine, Busulfan, Cyclophosphamide

Regimen

Study	Evidence
Glass et al. 2014 (DSHNHL R3)	Phase II

Chemotherapy

Fludarabine (Fludara) 25 mg/m²/day IV on days -8 to -4
Busulfan (Myleran) 4 mg/kg/day PO on days -6 to -4
Cyclophosphamide (Cytoxan) 60 mg/kg/day IV on days -3 and -2

Immunotherapy

Allogeneic stem cells transfused on day 0

GVHD prophylaxis

Antithymocyte globulin, rabbit ATG (Thymoglobulin) 2 mg/kg IV from day -3 to -1 (unclear if this is a total dose or a daily dose)
- Option also to use ATG-Fresenius S at a higher dose of 10 mg/kg
Tacrolimus (Prograf) 8 to 12 mcg/L (route/frequency not specified) starting on day -1, tapered from day +100 in absence of GVHD
Mycophenolate mofetil (CellCept) 1000 mg (route not specified) twice per day from day +1 to +28

One course

Immunotherapy

Allogeneic stem cells

Stem cells transfused on day 0

References

DSHNHL R3: Glass B, Hasenkamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M, Silling G, Wilhelm C, Zeis M, Görlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N; German High-Grade Lymphoma Study Group. Rituximab after lymphoma-directed conditioning and allogeneic stem-cell transplantation for relapsed and refractory aggressive non-Hodgkin lymphoma (DSHNHL R3): an open-label, randomised, phase 2 trial. Lancet Oncol. 2014 Jun;15(7):757-66. Epub 2014 May 11. link to original article link to original protocol (in German) contains verified protocol PubMed

Fludarabine, Busulfan, ATG, Ibritumomab tiuxetan, then allo HSCT

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Regimen

Study	Evidence
Bouabdallah et al. 2015 (ZEVALLO)	Phase II

Chemotherapy

Fludarabine (Fludara) 30 mg/m² IV once per day on days -6 to -2
Busulfan (Myleran) 3.2 mg/kg/day (route not specified) on days -5 & -4

Targeted therapy

Rituximab (Rituxan) 250 mg/m² IV once per day on days -21 & -14

Radioconjugate therapy

Ibritumomab tiuxetan (Zevalin) 0.4 mCi/kg (maximum dose of 32 mCi) IV once on day -14

Immunotherapy

Allogeneic stem cells transfused on day 0

GVHD prophylaxis

Antithymocyte globulin, rabbit ATG (Thymoglobulin) 2.5 mg/kg IV once on day -1
Cyclosporine (dose not specified) until day +90 and tapered off by day +180 based on chimerism and GVHD
Methotrexate (MTX) by the following donor-based criteria:
- Unrelated donors with HLA mismatch: 15 mg/m² (route not specified) once on day +1, then 10 mg/m² (route not specified) once per day on days +3 & +6

One course

Immunotherapy

Allogeneic stem cells

Stem cells transfused on day 0

References

ZEVALLO: Bouabdallah K, Furst S, Asselineau J, Chevalier P, Tournilhac O, Ceballos P, Vigouroux S, Tabrizi R, Doussau A, Bouabdallah R, Mohty M, Le Gouill S, Blaise D, Milpied N. 90Y-ibritumomab tiuxetan, fludarabine, busulfan and antithymocyte globulin reduced-intensity allogeneic transplant conditioning for patients with advanced and high-risk B-cell lymphomas. Ann Oncol. 2015 Jan;26(1):193-8. Epub 2014 Oct 30. link to original article contains verified protocol PubMed

LEED, then auto HSCT

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LEED: L-PAM (Melphalan), Endoxan (Cyclophosphamide), Etoposide, Dexamethasone

Regimen

Study	Evidence
van Imhoff et al. 2016 (ORCHARRD)	Non-randomized portion of RCT

Preceding treatment

O-DHAP x 3 versus R-DHAP x 3

Autologous HSCT conditioning regimens Stem cells reinfused on day 0

References

ORCHARRD: van Imhoff GW, McMillan A, Matasar MJ, Radford J, Ardeshna KM, Kuliczkowski K, Kim W, Hong X, Goerloev JS, Davies A, Barrigón MD, Ogura M, Leppä S, Fennessy M, Liao Q, van der Holt B, Lisby S, Hagenbeek A. Ofatumumab versus rituximab salvage chemoimmunotherapy in relapsed or refractory diffuse large B-cell lymphoma: the ORCHARRD study. J Clin Oncol. 2017 Feb 10;35(5):544-51. Epub 2016 Dec 28. link to original article link to data supplement verified protocol in supplement PubMed

R-BEAM, then auto HSCT

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R-BEAM: Rituximab, BiCNU (Carmustine), Etoposide, Ara-C (Cytarabine), Melphalan

Regimen variant #1, 750/300/800/800/140

Study	Evidence	Comparator	Comparative Efficacy
Vose et al. 2013 (BMT CTN 0401)	Phase III (C)	B-BEAM	Did not meet primary endpoint of PFS24

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.

Targeted therapy

Rituximab (Rituxan) 375 mg/m² IV once per day on days -19 & -12

Chemotherapy

Carmustine (BCNU) 300 mg/m² IV once on day -6
Etoposide (Vepesid) 100 mg/m² IV twice per day on days -5 to -2
Cytarabine (Ara-C) 100 mg/m² IV twice per day on days -5 to -2
Melphalan (Alkeran) 140 mg/m² IV once on day -1

Supportive therapy

Autologous stem cells re-infused on day 0

One course

Regimen variant #2, 750/300/1600/3200/140

Study	Evidence
Kirschey et al. 2014 (Mz-135)	Phase II

A minimum number of 2 × 10⁶/kg bw CD34-positive cells were required to proceed.

Preceding treatment

R-DexaBEAM x 2

Autologous HSCT conditioning regimens

References

BMT CTN 0401: Vose JM, Carter S, Burns LJ, Ayala E, Press OW, Moskowitz CH, Stadtmauer EA, Mineshi S, Ambinder R, Fenske T, Horowitz M, Fisher R, Tomblyn M. Phase III randomized study of rituximab/carmustine, etoposide, cytarabine, and melphalan (BEAM) compared with iodine-131 tositumomab/BEAM with autologous hematopoietic cell transplantation for relapsed diffuse large B-cell lymphoma: results from the BMT CTN 0401 trial. J Clin Oncol. 2013 May 1;31(13):1662-8. Epub 2013 Mar 11. link to original article link to PMC article contains verified protocol PubMed
Mz-135: Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. link to original article contains verified protocol PubMed

R-TBI/Cy, then auto HSCT

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R-TBI/Cy: Rituximab, Total, Body, Irradiation, Cyclophosphamide

Regimen

Study	Evidence
Kirschey et al. 2014 (Mz-135)	Phase II

Preceding treatment

R-DexaBEAM x 2

Autologous HSCT conditioning regimens Stem cells reinfused on day 0

References

Mz-135: Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. link to original article contains verified protocol PubMed

Z-BEAM, then auto HSCT

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Z-BEAM: Zevalin (Ibritumomab tiuxetan), BiCNU (Carmustine), Etoposide, Ara-C (Cytarabine), Melphalan

Regimen

Study	Evidence	Comparator	Comparative Efficacy
Shimoni et al. 2007	Phase II
Shimoni et al. 2012 (SHEBA-07-4466-AN-CTIL)	Randomized Phase II (E-esc)	BEAM	Seems to have superior OS
Briones et al. 2013 (GELTAMO Z-BEAM LDCGB)	Phase II

Patients in SHEBA-07-4466-AN-CTIL had primary induction failure or were chemosensitive to salvage therapy. Patients in GELTAMO Z-BEAM LDCGB had primary induction failure or were refractory to salvage therapy.

Targeted therapy

Rituximab (Rituxan) 250 mg/m² IV once on day -14, given first

Radioconjugate therapy

Ibritumomab tiuxetan & Yttrium-90 (Zevalin) 0.4 mCi/kg (maximum dose of 32 mCi) IV once on day -14, given second

Chemotherapy

Carmustine (BCNU) 300 mg/m² IV once on day -6
Etoposide (Vepesid) 200 mg/m² IV once per day on days -5 to -2
Cytarabine (Ara-C) 200 mg/m² IV every 12 hours on days -5 to -2
Melphalan (Alkeran) 140 mg/m² IV once on day -1

Supportive therapy

Autologous stem cells re-infused on day 0
Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day +4 (Shimoni et al. 2012) or day +7 (GELTAMO Z-BEAM LDCGB) until engraftment
Valacyclovir (Valtrex) (dose not specified) for one month (Shimoni et al. 2012)
Acyclovir (Zovirax) (dose not specified) for one month (Briones et al. 2013)
Trimethoprim-Sulfamethoxazole (Bactrim DS) (dose/frequency not specified) for six months (3 months in GELTAMO Z-BEAM LDCGB)

One course

References

Shimoni A, Zwas ST, Oksman Y, Hardan I, Shem-Tov N, Yerushalmi R, Avigdor A, Ben-Bassat I, Nagler A. Yttrium-90-ibritumomab tiuxetan (Zevalin) combined with high-dose BEAM chemotherapy and autologous stem cell transplantation for chemo-refractory aggressive non-Hodgkin's lymphoma. Exp Hematol. 2007 Apr;35(4):534-40. link to original article PubMed
SHEBA-07-4466-AN-CTIL: Shimoni A, Avivi I, Rowe JM, Yeshurun M, Levi I, Or R, Patachenko P, Avigdor A, Zwas T, Nagler A. A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma. Cancer. 2012 Oct 1;118(19):4706-14. Epub 2012 Jan 17. link to original article contains verified protocol PubMed
GELTAMO Z-BEAM LDCGB: Briones J, Novelli S, García-Marco JA, Tomás JF, Bernal T, Grande C, Canales MA, Torres A, Moraleda JM, Panizo C, Jarque I, Palmero F, Hernsández M, González-Barca E, López D, Caballero D. Autologous stem cell transplantation after conditioning with Yttrium-90 ibritumomab tiuxetan plus beam in refractory non-Hodgkin diffuse large B-cell lymphoma: results of a prospective, multicenter, phase II clinical trial. Haematologica. 2014 Mar;99(3):505-10. Epub 2013 Oct 25. link to original article contains verified protocol link to PMC article PubMed

Maintenance after salvage therapy

Lenalidomide monotherapy

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Regimen variant #1, 25 mg 21/28, indefinite

Study	Evidence
Ferreri et al. 2017	Phase II

Preceding treatment

Rituximab-containing salvage chemotherapy

Chemotherapy

Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21

28-day cycles

Regimen variant #2, 25 mg 21/28 for 12 months

Study	Evidence
Feldman et al. 2014 (RV-DLBCL-PI-0463)	Phase II

Preceding treatment

BEAM with autologous hematopoietic stem cell transplant (details not described)

Chemotherapy

Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21

28-day cycle for up to 13 cycles (1 year)

References

RV-DLBCL-PI-0463: Feldman T, Mato AR, Chow KF, Protomastro EA, Yannotti KM, Bhattacharyya P, Yang X, Donato ML, Rowley SD, Carini C, Valentinetti M, Smith J, Gadaleta G, Bejot C, Stives S, Timberg M, Kdiry S, Pecora AL, Beaven AW, Goy A. Addition of lenalidomide to rituximab, ifosfamide, carboplatin, etoposide (RICER) in first-relapse/primary refractory diffuse large B-cell lymphoma. Br J Haematol. 2014 Jul;166(1):77-83. Epub 2014 Mar 25. link to original article contains verified protocol link to PMC article PubMed
Ferreri AJ, Sassone M, Zaja F, Re A, Spina M, di Rocco A, Fabbri A, Stelitano C, Frezzato M, Rusconi C, Zambello R, Couto S, Ren Y, Arcari A, Bertoldero G, Nonis A, Scarfò L, Calimeri T, Cecchetti C, Chiozzotto M, Govi S, Ponzoni M. Lenalidomide maintenance in patients with relapsed diffuse large B-cell lymphoma who are not eligible for autologous stem cell transplantation: an open label, single-arm, multicentre phase 2 trial. Lancet Haematol. 2017 Mar;4(3):e137-e146. Epub 2017 Feb 17. link to original article contains protocol PubMed

Observation

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Regimen

Study	Evidence	Comparator	Comparative Efficacy
Thompson et al. 2008 (SWOG 9438)	Phase III (C)	IL-2	Did not meet primary endpoints of PFS/OS
Furman et al. 2011 (CALGB 9254)	Phase III (C)	Anti-B4-bR	Did not meet primary endpoint of EFS
Gisselbrecht et al. 2010 (CORAL)	Phase III (C)	Rituximab	Did not meet primary endpoint of EFS (*)

No further treatment. Reported efficacy for CORAL is based on the 2012 update.

Preceding treatment

SWOG 9438: Cyclophosphamide, Etoposide, TBI with autologous hematopoietic stem cell transplant
CORAL: BEAM with autologous hematopoietic stem cell transplant

References

SWOG 9438: Thompson JA, Fisher RI, Leblanc M, Forman SJ, Press OW, Unger JM, Nademanee AP, Stiff PJ, Petersdorf SH, Fefer A. Total body irradiation, etoposide, cyclophosphamide, and autologous peripheral blood stem-cell transplantation followed by randomization to therapy with interleukin-2 versus observation for patients with non-Hodgkin lymphoma: results of a phase 3 randomized trial by the Southwest Oncology Group (SWOG 9438). Blood. 2008 Apr 15;111(8):4048-54. Epub 2008 Feb 6. link to original article link to PMC article PubMed
CALGB 9254: Furman RR, Grossbard ML, Johnson JL, Pecora AL, Cassileth PA, Jung SH, Peterson BA, Nadler LM, Freedman A, Bayer RL, Bartlett NL, Hurd DD, Cheson BD; Cancer Leukemia Group B; Eastern Cooperative Oncology Group. A phase III study of anti-B4-blocked ricin as adjuvant therapy post-autologous bone marrow transplant: CALGB 9254. Leuk Lymphoma. 2011 Apr;52(4):587-96. Epub 2011 Jan 28. link to original article link to PMC article PubMed
CORAL: Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Brière J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. Epub 2010 Jul 26. Erratum in: J Clin Oncol. 2012 May 20;30(15):1896. link to original article contains verified protocol link to PMC article PubMed
1. Update: Gisselbrecht C, Schmitz N, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Milpied NJ, Radford J, Ketterer N, Shpilberg O, Dührsen U, Hagberg H, Ma DD, Viardot A, Lowenthal R, Brière J, Salles G, Moskowitz CH, Glass B. Rituximab maintenance therapy after autologous stem-cell transplantation in patients with relapsed CD20(+) diffuse large B-cell lymphoma: final analysis of the collaborative trial in relapsed aggressive lymphoma. J Clin Oncol. 2012 Dec 20;30(36):4462-9. Epub 2012 Oct 22. link to original article contains verified protocol link to PMC article PubMed

Rituximab monotherapy

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Regimen

Study	Evidence	Comparator	Comparative Efficacy
Gisselbrecht et al. 2010 (CORAL)	Phase III (E-esc)	Observation	Did not meet primary endpoint of EFS (*)

Treatment begins on day +28. Reported efficacy is based on the 2012 update.

Preceding treatment

BEAM with autologous hematopoietic stem cell transplant

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1

8-week cycle for 6 cycles

References

CORAL: Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Brière J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. Epub 2010 Jul 26. Erratum in: J Clin Oncol. 2012 May 20;30(15):1896. link to original article contains verified protocol link to PMC article PubMed
1. Update: Gisselbrecht C, Schmitz N, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Milpied NJ, Radford J, Ketterer N, Shpilberg O, Dührsen U, Hagberg H, Ma DD, Viardot A, Lowenthal R, Brière J, Salles G, Moskowitz CH, Glass B. Rituximab maintenance therapy after autologous stem-cell transplantation in patients with relapsed CD20(+) diffuse large B-cell lymphoma: final analysis of the collaborative trial in relapsed aggressive lymphoma. J Clin Oncol. 2012 Dec 20;30(36):4462-9. Epub 2012 Oct 22. link to original article contains verified protocol link to PMC article PubMed

Relapsed or refractory, further lines of therapy

Note: these are regimens that are generally given with non-curative intent. However, some of these regimens, such as CAR-T therapy, can function as a bridge to consolidation with one of the salvage consolidation regimens, above.

Axicabtagene ciloleucel monotherapy

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Regimen

FDA-recommended dose

Study	Years of enrollment	Evidence	Efficacy
Locke et al. 2017 (ZUMA-1)		Phase 1
Nellapu et al. 2017 (ZUMA-1)	2015-2016	Phase II (RT)	ORR: 82%

Preceding treatment

Lymphodepletion with FC

Immunotherapy

Axicabtagene ciloleucel (Yescarta) target dose of 2 × 10⁶ CAR T cells/kg IV once on day 0

Supportive medications

Acetaminophen (Tylenol) 650 mg PO once on day 0, approximately 60 minutes prior to Axicabtagene ciloleucel (Yescarta)
Diphenhydramine (Benadryl) 12.5 mg IV or PO once on day 0, approximately 60 minutes prior to Axicabtagene ciloleucel (Yescarta)

One course; patients with initial response and disease progression at least 3 months later could be retreated

References

Phase 1: Locke FL, Neelapu SS, Bartlett NL, Siddiqi T, Chavez JC, Hosing CM, Ghobadi A, Budde LE, Bot A, Rossi JM, Jiang Y, Xue AX, Elias M, Aycock J, Wiezorek J, Go WY. Phase 1 results of ZUMA-1: A multicenter study of KTE-C19 anti-CD19 CAR T cell therapy in refractory aggressive lymphoma. Mol Ther. 2017 Jan 4;25(1):285-295. Epub 2017 Jan 4. link to original article link to PMC article PubMed
ZUMA-1: Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang D, Wiezorek J, Go WY. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017 Dec 28;377(26):2531-2544. Epub 2017 Dec 10. link to original article contains verified protocol link to PMC article PubMed

Bendamustine monotherapy

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Regimen

Study	Evidence	Efficacy
Weidmann et al. 2002	Phase II, <20 pts	44%

Chemotherapy

Bendamustine 120 mg/m² IV once per day on days 1 & 2

21-day cycle for up to 6 cycles

References

Weidmann E, Kim SZ, Rost A, Schuppert H, Seipelt G, Hoelzer D, Mitrou PS. Bendamustine is effective in relapsed or refractory aggressive non-Hodgkin's lymphoma. Ann Oncol. 2002 Aug;13(8):1285-9. link to original article contains verified protocol PubMed

Blinatumomab monotherapy

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Regimen

Study	Evidence
Viardot et al. 2016 (MT103-208)	Phase II

Two dosing schemas were evaluated; this is the preferred dosing regimen, per the authors.

Chemotherapy

Blinatumomab (Blincyto) as follows:
- 9 mcg/day IV continuous infusion during week 1, then
- 28 mcg/day IV continuous infusion during week 2, then
- 112 mcg/day IV continuous infusion for remainder of the 8-week course

Supportive medications

Dexamethasone (Decadron) 20 mg PO 6 to 12 hours before infusion start and dose increases, 20 mg PO 1 hour before infusion start and dose increases, and 8 mg PO three times per day for 2 days following infusion start and dose increases
- Patients with neurologic symptoms or cytokine release syndrome received 8 mg IV or PO every 8 hours for up to 3 days, with a subsequent taper over 4 days

8-week course

Responders could receive a 4-week consolidation cycle after a 4-week treatment-free period. Patients relapsing within 2 years of treatment could receive another 8-week course.

References

MT103-208: Viardot A, Goebeler ME, Hess G, Neumann S, Pfreundschuh M, Adrian N, Zettl F, Libicher M, Sayehli C, Stieglmaier J, Zhang A, Nagorsen D, Bargou RC. Phase 2 study of the bispecific T-cell engager (BiTE) antibody blinatumomab in relapsed/refractory diffuse large B-cell lymphoma. Blood. 2016 Mar 17;127(11):1410-6. Epub 2016 Jan 11. link to original article contains verified protocol link to PMC article PubMed

BR

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BR: Bendamustine & Rituximab R-B: Rituximab & Bendamustine

Regimen variant #1, 6 cycles

Study	Evidence
Ohmachi et al. 2013 (SymBio 2010001)	Phase II
Vacirca et al. 2013 (PI-08904)	Phase II

Note: Bendamustine was given on days 2 & 3 in SymBio 2010001 and on days 1 & 2 in PI-08904.

Chemotherapy

Bendamustine 120 mg/m² IV once per day on days 1 & 2 OR on days 2 & 3
Rituximab (Rituxan) 375 mg/m² IV once on day 1

Supportive medications

Recommended PCP prophylaxis: Trimethoprim-Sulfamethoxazole (Bactrim DS)
Recommended VZV prophylaxis: Acyclovir (Zovirax)

21-day cycle for up to 6 cycles

Regimen variant #2, indefinite

Study	Evidence	Comparator	Comparative Efficacy
Dang et al. 2017 (B1931008)	Phase III (C)	R-INO	Did not meet primary endpoint of OS

Chemotherapy

Bendamustine 120 mg/m² IV once per day on days 1 & 2
Rituximab (Rituxan) 375 mg/m² IV once on day 1

28-day cycles

References

SymBio 2010001: Ohmachi K, Niitsu N, Uchida T, Kim SJ, Ando K, Takahashi N, Takahashi N, Uike N, Eom HS, Chae YS, Terauchi T, Tateishi U, Tatsumi M, Kim WS, Tobinai K, Suh C, Ogura M. Multicenter phase II study of bendamustine plus rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol. 2013 Jun 10;31(17):2103-9. Epub 2013 May 6. link to original article contains verified protocol PubMed
PI-08904: Vacirca JL, Acs PI, Tabbara IA, Rosen PJ, Lee P, Lynam E. Bendamustine combined with rituximab for patients with relapsed or refractory diffuse large B cell lymphoma. Ann Hematol. 2014 Mar;93(3):403-9. Epub 2013 Aug 17. link to original article contains verified protocol link to PMC article PubMed
B1931008: Dang NH, Ogura M, Castaigne S, Fayad LE, Jerkeman M, Radford J, Pezzutto A, Bondarenko I, Stewart DA, Shnaidman M, Sullivan S, Vandendries E, Tobinai K, Ramchandren R, Hamlin PA, Giné E, Ando K. Randomized, phase 3 trial of inotuzumab ozogamicin plus rituximab versus chemotherapy plus rituximab for relapsed/refractory aggressive B-cell non-Hodgkin lymphoma. Br J Haematol. 2018 Aug;182(4):583-586. Epub 2017 Jul 5. link to original article link to PMC article contains protocol PubMed

BR & Polatuzumab vedotin

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BR & Polatuzumab vedotin: Bendamustine, Rituximab, Polatuzumab vedotin

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
GO29365	2014-2016	Randomized Phase II (E-RT-esc)	BR	Seems to have superior ORR

Chemotherapy

Bendamustine as follows:
- Cycle 1: 90 mg/m² IV once per day on days 2 & 3
- Cycles 2 to 6: 90 mg/m² IV once per day on days 1 & 2
Rituximab (Rituxan) 375 mg/m² IV once on day 1
Polatuzumab vedotin (Polivy) as follows:
- Cycle 1: 1.8 mg/kg IV over 90 minutes once on day 2
- Cycles 2 to 6: 1.8 mg/kg IV over 90 minutes once on day 1

References

GO29365: Sehn LH, Herrera AF, Flowers CR, Kamdar MK, McMillan A, Hertzberg M, Assouline S, Kim TM, Kim WS, Ozcan M, Hirata J, Penuel E, Paulson JN, Cheng J, Ku G, Matasar MJ. Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. J Clin Oncol. 2020 Jan 10; 38(2):155-165. Epub 2019 Nov 6. link to original article link to pubmed CT.gov

Brentuximab vedotin monotherapy

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Regimen

Study	Evidence
Jacobsen et al. 2015 (SGN35-012)	Phase II

Jacobsen et al. 2015 treated patients with CD30+ non-Hodgkin lymphoma, as determined by IHC; the 2016 update describes a subgroup with undetectable CD30.

Chemotherapy

Brentuximab vedotin (Adcetris) 1.8 mg/kg IV over 30 minutes once on day 1

21-day cycles

References

SGN35-012: Jacobsen ED, Sharman JP, Oki Y, Advani RH, Winter JN, Bello CM, Spitzer G, Palanca-Wessels MC, Kennedy DA, Levine P, Yang J, Bartlett NL. Brentuximab vedotin demonstrates objective responses in a phase 2 study of relapsed/refractory DLBCL with variable CD30 expression. Blood. 2015 Feb 26;125(9):1394-402. Epub 2015 Jan 8. link to original article contains verified protocol PubMed
1. Update: Bartlett NL, Smith MR, Siddiqi T, Advani RH, O'Connor OA, Sharman JP, Feldman T, Savage KJ, Shustov AR, Diefenbach CS, Oki Y, Palanca-Wessels MC, Uttarwar M, Li M, Yang J, Jacobsen ED. Brentuximab vedotin activity in diffuse large B-cell lymphoma with CD30 undetectable by visual assessment of conventional immunohistochemistry. Leuk Lymphoma. 2017 Jul;58(7):1607-1616. Epub 2016 Nov 20. link to original article PubMed

Etoposide monotherapy

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Regimen variant #1, IV (3 days/cycle)

Study	Evidence	Comparator	Comparative Efficacy
Czuczman et al. 2017 (DLC-001)	Phase II/III (C)	Lenalidomide	Might have inferior ORR

Chemotherapy

Etoposide (Vepesid) 100 mg/m² IV once per day on days 1 to 3

28-day cycle for up to 6 cycles

Regimen variant #2, IV (5 days/cycle)

Study	Evidence	Comparator	Comparative Efficacy
Pettengell et al. 2012 (PIX301)	Phase III, <20 pts in this arm (C)	Pixantrone	Seems to have inferior CR/CRu rate
Czuczman et al. 2017 (DLC-001)	Phase II/III (C)	Lenalidomide	Might have inferior ORR

Chemotherapy

Etoposide (Vepesid) 100 mg/m² IV once per day on days 1 to 5

28-day cycle for up to 6 cycles

Regimen variant #3, PO (10 days/cycle)

Study	Evidence	Comparator	Comparative Efficacy
Czuczman et al. 2017 (DLC-001)	Phase II/III (C)	Lenalidomide	Might have inferior ORR

Chemotherapy

Etoposide (Vepesid) 50 mg/m² PO once per day on days 1 to 10

28-day cycle for up to 6 cycles

Regimen variant #4, PO (14 days/cycle)

Study	Evidence	Comparator	Comparative Efficacy
Czuczman et al. 2017 (DLC-001)	Phase II/III (C)	Lenalidomide	Might have inferior ORR

Chemotherapy

Etoposide (Vepesid) 50 mg/m² PO once per day on days 1 to 14

28-day cycle for up to 6 cycles

Regimen variant #5, PO (21 days/cycle)

Study	Evidence	Comparator	Comparative Efficacy
Hainsworth et al. 1992	Phase II
Pettengell et al. 2012 (PIX301)	Phase III, <20 pts in this arm (C)	Pixantrone	Seems to have inferior CR/CRu rate
Czuczman et al. 2017 (DLC-001)	Phase II/III (C)	Lenalidomide	Might have inferior ORR

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.

Chemotherapy

Etoposide (Vepesid) 50 mg/m² PO once per day on days 1 to 21

28-day cycle for up to 6 cycles

References

Hainsworth JD, Johnson DH, Greco FA. Chronic etoposide schedules in the treatment of non-Hodgkin's lymphoma. Semin Oncol. 1992 Dec;19(6 Suppl 14):13-8. link to original article PubMed
PIX301: Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. link to original article contains verified protocol PubMed
DLC-001: Czuczman MS, Trněný M, Davies A, Rule S, Linton KM, Wagner-Johnston N, Gascoyne RD, Slack GW, Brousset P, Eberhard DA, Hernandez-Ilizaliturri FJ, Salles G, Witzig TE, Zinzani PL, Wright GW, Staudt LM, Yang Y, Williams PM, Lih CJ, Russo J, Thakurta A, Hagner P, Fustier P, Song D, Lewis ID. A phase 2/3 multicenter, randomized, open-label study to compare the efficacy and safety of lenalidomide versus investigator's choice in patients with relapsed or refractory diffuse large B-cell lymphoma. Clin Cancer Res. 2017 Aug 1;23(15):4127-4137. Epub 2017 Apr 5. link to original article contains verified protocol in supplement PubMed

Everolimus monotherapy

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Regimen

Study	Evidence
Witzig et al. 2011	Phase II

Chemotherapy

Everolimus (Afinitor) 10 mg PO once per day on an empty stomach

Supportive medications

"Patients could receive white blood cell growth factors, if neutropenia developed at physician's discretion. Erythropoietin treatment for anemia was permitted per standard guidelines."

28-day cycles

References

Witzig TE, Reeder CB, LaPlant BR, Gupta M, Johnston PB, Micallef IN, Porrata LF, Ansell SM, Colgan JP, Jacobsen ED, Ghobrial IM, Habermann TM. A phase II trial of the oral mTOR inhibitor everolimus in relapsed aggressive lymphoma. Leukemia. 2011 Feb;25(2):341-7. Epub 2010 Dec 7. link to original article contains verified protocol link to PMC article PubMed

Everolimus & Rituximab

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Regimen

Study	Evidence
Barnes et al. 2013 (MGH 09-002)	Phase II

Chemotherapy

Everolimus (Afinitor) as follows:
- Cycle 1: 5 mg PO once per day on days 1 to 14, then 10 mg PO once per day on days 15 to 28
- Cycles 2 to 6: 10 mg PO once per day
Rituximab (Rituxan) as follows:
- Cycle 1: 375 mg/m² IV once per day on days 1, 8, 15, 22
- Cycles 2 to 6: 375 mg/m² IV once on day 1

28-day cycle for 6 cycles

Subsequent treatment

Responders had the option of continuing everolimus alone for another 6 months

References

MGH 09-002: Barnes JA, Jacobsen E, Feng Y, Freedman A, Hochberg EP, LaCasce AS, Armand P, Joyce R, Sohani AR, Rodig SJ, Neuberg D, Fisher DC, Abramson JS. Everolimus in combination with rituximab induces complete responses in heavily pretreated diffuse large B-cell lymphoma. Haematologica. 2013 Apr;98(4):615-9. Epub 2012 Nov 9. link to original article contains verified protocol link to PMC article PubMed

Gemcitabine monotherapy

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Regimen variant #1, bi-weekly

Study	Evidence	Comparator	Comparative Efficacy
Czuczman et al. 2017 (DLC-001)	Phase II/III (C)	Lenalidomide	Might have inferior ORR

Chemotherapy

Gemcitabine (Gemzar) 1000 mg/m² IV once per day on days 1 & 15

28-day cycle for up to 6 cycles

Regimen variant #2, 3 out of 4 weeks x 6

Study	Evidence	Comparator	Comparative Efficacy
Czuczman et al. 2017 (DLC-001)	Phase II/III (C)	Lenalidomide	Might have inferior ORR

Chemotherapy

Gemcitabine (Gemzar) 1250 mg/m² IV once per day on days 1, 8, 15

28-day cycle for up to 6 cycles

Regimen variant #3, indefinite 3 out of 4 weeks

Study	Evidence	Comparator	Comparative Efficacy
Fosså et al. 1999	Phase II
Pettengell et al. 2012 (PIX301)	Phase III, <20 pts in this arm (C)	Pixantrone	Seems to have inferior CR/CRu rate

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.

Chemotherapy

Gemcitabine (Gemzar) as follows:
- Cycle 1: 1250 mg/m² IV over 30 minutes once per day on days 1, 8, 15
- Fosså et al. 1999, subsequent cycles (if no hematologic or nonhematologic toxicities): Optional increase to 1500 mg/m² IV over 30 minutes once per day on days 1, 8, 15

28-day cycle for up to 6 cycles (PIX301) or indefinitely (Fosså et al. 1999)

References

Fosså A, Santoro A, Hiddemann W, Truemper L, Niederle N, Buksmaui S, Bonadonna G, Seeber S, Nowrousian MR. Gemcitabine as a single agent in the treatment of relapsed or refractory aggressive non-Hodgkin's lymphoma. J Clin Oncol. 1999 Dec;17(12):3786-92. link to original article contains verified protocol PubMed
PIX301: Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. link to original article contains verified protocol PubMed
DLC-001: Czuczman MS, Trněný M, Davies A, Rule S, Linton KM, Wagner-Johnston N, Gascoyne RD, Slack GW, Brousset P, Eberhard DA, Hernandez-Ilizaliturri FJ, Salles G, Witzig TE, Zinzani PL, Wright GW, Staudt LM, Yang Y, Williams PM, Lih CJ, Russo J, Thakurta A, Hagner P, Fustier P, Song D, Lewis ID. A phase 2/3 multicenter, randomized, open-label study to compare the efficacy and safety of lenalidomide versus investigator's choice in patients with relapsed or refractory diffuse large B-cell lymphoma. Clin Cancer Res. 2017 Aug 1;23(15):4127-4137. Epub 2017 Apr 5. link to original article contains verified protocol in supplement PubMed

Gemcitabine & Rituximab

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R-G: Rituximab & Gemcitabine

Regimen

Study	Evidence	Comparator	Comparative Efficacy
Dang et al. 2017 (B1931008)	Phase III (C)	R-INO	Did not meet primary endpoint of OS

Chemotherapy

Gemcitabine (Gemzar) 1000 mg/m² IV once per day on days 1, 8, 15
Rituximab (Rituxan) as follows:
- Cycle 1: 375 mg/m² IV once per day on days 1, 8, 15, 22
- Cycle 2 onwards: 375 mg/m² IV once on day 1

28-day cycles

References

B1931008: Dang NH, Ogura M, Castaigne S, Fayad LE, Jerkeman M, Radford J, Pezzutto A, Bondarenko I, Stewart DA, Shnaidman M, Sullivan S, Vandendries E, Tobinai K, Ramchandren R, Hamlin PA, Giné E, Ando K. Randomized, phase 3 trial of inotuzumab ozogamicin plus rituximab versus chemotherapy plus rituximab for relapsed/refractory aggressive B-cell non-Hodgkin lymphoma. Br J Haematol. 2018 Aug;182(4):583-586. Epub 2017 Jul 5. link to original article link to PMC article contains protocol PubMed

GVD

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GVD: Gemcitabine, Vinorelbine, Doxil (Doxorubicin liposomal)

Regimen

Study	Evidence
Bai et al. 2013	Retrospective

Chemotherapy

Gemcitabine (Gemzar) 800 mg/m² IV once on day 1
Vinorelbine (Navelbine) 15 mg/m² IV once on day 1
Pegylated liposomal doxorubicin (Doxil) 20 mg/m² IV once on day 1

14-day cycles

References

Retrospective: Bai B, Huang HQ, Cai QQ, Wang XX, Cai QC, Lin ZX, Gao Y, Xia Y, Bu Q, Guo Y. Promising long-term outcome of gemcitabine, vinorelbine, liposomal doxorubicin (GVD) in 14-day schedule as salvage regimen for patients with previously heavily treated Hodgkin's lymphoma and aggressive non-Hodgkin's lymphoma. Med Oncol. 2013 Mar;30(1):350. Epub 2013 Jan 18. link to original article contains protocol PubMed

Ibritumomab tiuxetan monotherapy

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Regimen

Study	Evidence
Morschhauser et al. 2007	Phase II

To be completed

Radioimmunotherapy

Ibritumomab tiuxetan & Yttrium-90 (Zevalin)

References

Morschhauser F, Illidge T, Huglo D, Martinelli G, Paganelli G, Zinzani PL, Rule S, Liberati AM, Milpied N, Hess G, Stein H, Kalmus J, Marcus R. Efficacy and safety of yttrium-90 ibritumomab tiuxetan in patients with relapsed or refractory diffuse large B-cell lymphoma not appropriate for autologous stem-cell transplantation. Blood. 2007 Jul 1;110(1):54-8. Epub 2007 Mar 26. link to original article PubMed

Ibrutinib monotherapy

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Regimen

Study	Evidence
Wilson et al. 2015 (PCYC-1106-CA)	Phase II

Clinically meaningful responses were observed in the ABC subtype, only. Further clinical trials are currently underway.

Chemotherapy

Ibrutinib (Imbruvica) 560 mg PO once per day

Continued indefinitely

References

PCYC-1106-CA: Wilson WH, Young RM, Schmitz R, Yang Y, Pittaluga S, Wright G, Lih CJ, Williams PM, Shaffer AL, Gerecitano J, de Vos S, Goy A, Kenkre VP, Barr PM, Blum KA, Shustov A, Advani R, Fowler NH, Vose JM, Elstrom RL, Habermann TM, Barrientos JC, McGreivy J, Fardis M, Chang BY, Clow F, Munneke B, Moussa D, Beaupre DM, Staudt LM. Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma. Nat Med. 2015 Aug;21(8):922-6. Epub 2015 Jul 20. link to original article PubMed

Ifosfamide monotherapy

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Regimen

Study	Evidence	Comparator	Comparative Efficacy
Case et al. 1991 (CALGB 8552)	Phase II
Pettengell et al. 2012 (PIX301)	Phase III, <20 pts in this arm (C)	Pixantrone	Seems to have inferior CR/CRu rate

Dose & schedule is as given in Pettengell et al. 2012. CALGB 8552 used a different dose & schedule. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.

Chemotherapy

Ifosfamide (Ifex) 3000 mg/m² IV once per day on days 1 & 2

Supportive medications

Mesna (Mesnex) dose not specified

28-day cycle for up to 6 cycles

References

CALGB 8552: Case DC Jr, Anderson J, Ervin TJ, Gottlieb A. Phase II trial of ifosfamide and mesna in previously treated patients with non-Hodgkin's lymphoma: Cancer and Leukemia Group B study 8552. Hematol Oncol. 1991 Jul-Oct;9(4-5):189-96. PubMed
Review: Webb MS, Saltman DL, Connors JM, Goldie JH. A literature review of single agent treatment of multiply relapsed aggressive non-Hodgkin's lymphoma. Leuk Lymphoma. 2002 May;43(5):975-82. link to original article PubMed
PIX301: Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. link to original article contains verified protocol PubMed

Lenalidomide monotherapy

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Regimen variant #1, low dose

Study	Evidence	Comparator	Comparative Efficacy
Czuczman et al. 2017 (DLC-001)	Phase II/III (E-switch-ooc)	Investigator's choice of: 1. Etoposide 2. Gemcitabine 3. Oxaliplatin 4. Rituximab	Might have superior ORR

This dose was intended for patients with CrCl at least 30 but less than 60 mL/min/1.73m².

Chemotherapy

Lenalidomide (Revlimid) 10 mg PO once per day on days 1 to 21

28-day cycles

Regimen variant #2, normal dose

Study	Evidence	Comparator	Comparative Efficacy
Wiernik et al. 2008 (NHL-002)	Phase II		ORR: 35%
Witzig et al. 2011 (NHL-003)	Phase II		ORR: 28%
Czuczman et al. 2017 (DLC-001)	Phase II/III (E-switch-ooc)	Investigator's choice of: 1. Etoposide 2. Gemcitabine 3. Oxaliplatin 4. Rituximab	Might have superior ORR

Chemotherapy

Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21

28-day cycles

References

NHL-002: Wiernik PH, Lossos IS, Tuscano JM, Justice G, Vose JM, Cole CE, Lam W, McBride K, Wride K, Pietronigro D, Takeshita K, Ervin-Haynes A, Zeldis JB, Habermann TM. Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin's lymphoma. J Clin Oncol. 2008 Oct 20;26(30):4952-7. Epub 2008 Jul 7. link to original article contains verified protocol PubMed
NHL-003: Witzig TE, Vose JM, Zinzani PL, Reeder CB, Buckstein R, Polikoff JA, Bouabdallah R, Haioun C, Tilly H, Guo P, Pietronigro D, Ervin-Haynes AL, Czuczman MS. An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma. Ann Oncol. 2011 Jul;22(7):1622-7. Epub 2011 Jan 12. link to original article contains verified protocol PubMed
DLC-001: Czuczman MS, Trněný M, Davies A, Rule S, Linton KM, Wagner-Johnston N, Gascoyne RD, Slack GW, Brousset P, Eberhard DA, Hernandez-Ilizaliturri FJ, Salles G, Witzig TE, Zinzani PL, Wright GW, Staudt LM, Yang Y, Williams PM, Lih CJ, Russo J, Thakurta A, Hagner P, Fustier P, Song D, Lewis ID. A phase 2/3 multicenter, randomized, open-label study to compare the efficacy and safety of lenalidomide versus investigator's choice in patients with relapsed or refractory diffuse large B-cell lymphoma. Clin Cancer Res. 2017 Aug 1;23(15):4127-4137. Epub 2017 Apr 5. link to original article contains verified protocol PubMed

Lenalidomide & Rituximab

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Regimen variant #1

Study	Evidence
Wang et al. 2013 (MDACC 2005-0461)	Phase II

Chemotherapy

Lenalidomide (Revlimid) 20 mg PO once per day on days 1 to 21
Rituximab (Rituxan) as follows:
- Cycle 1: 375 mg/m² IV once per day on days 1, 8, 15, 22

28-day cycles

Regimen variant #2

Study	Evidence
Zinzani et al. 2011a	Phase II

Chemotherapy

Lenalidomide (Revlimid) 20 mg PO once per day on days 1 to 21
Rituximab (Rituxan) 375 mg/m² IV once per day on days 1 & 21

28-day cycle for 4 cycles

Subsequent treatment

SD or better: Lenalidomide maintenance

References

Zinzani PL, Pellegrini C, Gandolfi L, Stefoni V, Quirini F, Derenzini E, Broccoli A, Argnani L, Pileri S, Baccarani M. Combination of lenalidomide and rituximab in elderly patients with relapsed or refractory diffuse large B-cell lymphoma: a phase 2 trial. Clin Lymphoma Myeloma Leuk. 2011 Dec;11(6):462-6. Epub 2011 May 4. link to original article contains verified protocol PubMed
1. Update: Zinzani PL, Pellegrini C, Derenzini E, Argnani L, Pileri S. Long-term efficacy of the combination of lenalidomide and rituximab in elderly relapsed/refractory diffuse large B-cell lymphoma patients. Hematol Oncol. 2013 Dec;31(4):223-4. Epub 2013 Apr 26. link to original article PubMed
MDACC 2005-0461: Wang M, Fowler N, Wagner-Bartak N, Feng L, Romaguera J, Neelapu SS, Hagemeister F, Fanale M, Oki Y, Pro B, Shah J, Thomas S, Younes A, Hosing C, Zhang L, Newberry KJ, Desai M, Cheng N, Badillo M, Bejarano M, Chen Y, Young KH, Champlin R, Kwak L, Fayad L. Oral lenalidomide with rituximab in relapsed or refractory diffuse large cell, follicular and transformed lymphoma: a phase II clinical trial. Leukemia. 2013 Sep;27(9):1902-9. Epub 2013 Apr 2. link to original article contains verified protocol PubMed

Mitoxantrone monotherapy

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Regimen

Study	Evidence
Bajetta et al. 1988a	Phase II

Chemotherapy

Mitoxantrone (Novantrone) 14 mg/m² IV over 30 minutes once on day 1

21-day cycles

References

Bajetta E, Buzzoni R, Valagussa P, Bonadonna G. Mitoxantrone: an active agent in refractory non-Hodgkin's lymphomas. Am J Clin Oncol. 1988 Apr;11(2):100-3. contains protocol PubMed
PIX301: Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. link to original article contains verified protocol PubMed

Obinutuzumab monotherapy

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Regimen

Study	Evidence
Salles et al. 2012 (GAUGUIN)	Phase I/II

Note: this is the phase II dosing reported in Morschhauser et al. 2013.

Chemotherapy

Obinutuzumab (Gazyva) as follows:
- Cycle 1: 1600 mg (diluted to 10 mg/mL) IV once per day on days 1 & 8
- Cycles 2 to 8: 800 mg IV once on day 1
- Initial infusion rate is 50 mg/hour. In the absence of infusion-related reactions (IRRs), the rate is then increased by 50 mg/hour every 30 minutes, up to a maximum of 400 mg/hour.

Supportive medications

Acetaminophen (Tylenol) or paracetamol 650 to 1000 mg PO once per infusion, 30 minutes prior to Obinutuzumab (Gazyva)
"An antihistamine" once per infusion, 30 minutes prior to Obinutuzumab (Gazyva)
- If there were no infusion-related reactions (IRRs) requiring medication or infusion interruption, antihistamine could be omitted for subsequent infusions
Premedication with corticosteroids recommended for patients at high risk of infusion-related reactions (IRRs)
Use of G-CSF allowed for severe neutropenia
Antibiotic prophylaxis allowed

21-day cycle for 8 cycles

References

GAUGUIN: Salles G, Morschhauser F, Lamy T, Milpied N, Thieblemont C, Tilly H, Bieska G, Asikanius E, Carlile D, Birkett J, Pisa P, Cartron G. Phase 1 study results of the type II glycoengineered humanized anti-CD20 monoclonal antibody obinutuzumab (GA101) in B-cell lymphoma patients. Blood. 2012 May 31;119(22):5126-32. Epub 2012 Mar 19. link to original article PubMed
1. Subgroup analysis: Morschhauser FA, Cartron G, Thieblemont C, Solal-Céligny P, Haioun C, Bouabdallah R, Feugier P, Bouabdallah K, Asikanius E, Lei G, Wenger M, Wassner-Fritsch E, Salles GA. Obinutuzumab (GA101) monotherapy in relapsed/refractory diffuse large B-cell lymphoma or mantle-cell lymphoma: results from the phase II GAUGUIN study. J Clin Oncol. 2013 Aug 10;31(23):2912-9. Epub 2013 Jul 8. link to original article contains verified protocol PubMed
2. Subgroup analysis: Salles GA, Morschhauser F, Solal-Céligny P, Thieblemont C, Lamy T, Tilly H, Gyan E, Lei G, Wenger M, Wassner-Fritsch E, Cartron G. Obinutuzumab (GA101) in patients with relapsed/refractory indolent non-Hodgkin lymphoma: results from the phase II GAUGUIN study. J Clin Oncol. 2013 Aug 10;31(23):2920-6. Epub 2013 Jul 8. link to original article contains verified protocol PubMed
3. Subgroup analysis: Cartron G, de Guibert S, Dilhuydy MS, Morschhauser F, Leblond V, Dupuis J, Mahe B, Bouabdallah R, Lei G, Wenger M, Wassner-Fritsch E, Hallek M. Obinutuzumab (GA101) in relapsed/refractory chronic lymphocytic leukemia: final data from the phase 1/2 GAUGUIN study. Blood. 2014 Oct 2;124(14):2196-202. Epub 2014 Aug 20. link to original article contains verified protocol PubMed

Ofatumumab monotherapy

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Regimen

Study	Evidence
Coiffier et al. 2013 (415 Study)	Phase II

Chemotherapy

Ofatumumab (Arzerra) as follows:
- Cycle 1: 300 mg IV once on day 1, then 1000 mg IV once per day on days 8, 15, 22
- Cycle 2: 1000 mg IV once per day on days 1, 8, 15, 22

Supportive medications

Acetaminophen (Tylenol) (or equivalent) 1000 mg PO once per day on days 1, 8, 15, 22; 30 minutes to 2 hours prior to Ofatumumab (Arzerra)
Cetirizine (Zyrtec) (or equivalent) 10 mg PO once per day on days 1, 8, 15, 22; 30 minutes to 2 hours prior to Ofatumumab (Arzerra)
Prednisolone (Millipred) (or equivalent) 100 mg (route not specified) once per day on days 1 & 8; 30 minutes to 2 hours prior to Ofatumumab (Arzerra) for first 2 infusions, only

28-day cycle for 2 cycles

References

415 Study: Coiffier B, Radford J, Bosly A, Martinelli G, Verhoef G, Barca G, Davies A, Decaudin D, Gallop-Evans E, Padmanabhan-Iyer S, Van Eygen K, Wu KL, Gupta IV, Lin TS, Goldstein N, Jewell RC, Winter P, Lisby S; 415 study investigators. A multicentre, phase II trial of ofatumumab monotherapy in relapsed/progressive diffuse large B-cell lymphoma. Br J Haematol. 2013 Nov;163(3):334-42. Epub 2013 Aug 23. link to original article contains verified protocol PubMed

Oxaliplatin monotherapy

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Regimen variant #1, 100 mg/m²

Study	Evidence	Comparator	Comparative Efficacy
Germann et al. 1999	Phase II, <20 pts in this subgroup
Pettengell et al. 2012 (PIX301)	Phase III, <20 pts in this arm (C)	Pixantrone	Seems to have inferior CR/CRu rate
Czuczman et al. 2017 (DLC-001)	Phase II/III (C)	Lenalidomide	Might have inferior ORR

Germann et al. give a range of 100 to 130 mg/m². To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.

Chemotherapy

Oxaliplatin (Eloxatin) 100 mg/m² IV once on day 1

21-day cycles (maximum of 6 cycles in PIX301 & DLC-001)

Regimen variant #2, 130 mg/m²

Study	Evidence	Efficacy
Germann et al. 1999	Phase II, <20 pts in this subgroup
Oki et al. 2005	Phase II	ORR: 27% (95% CI, 13–47)

Germann et al. give a range of 100 to 130 mg/m².

Chemotherapy

Oxaliplatin (Eloxatin) 130 mg/m² IV once on day 1

21-day cycles

References

Germann N, Brienza S, Rotarski M, Emile JF, Di Palma M, Musset M, Reynes M, Soulié P, Cvitkovic E, Misset JL. Preliminary results on the activity of oxaliplatin (L-OHP) in refractory/recurrent non-Hodgkin's lymphoma patients. Ann Oncol. 1999 Mar;10(3):351-4. link to original article contains verified protocol PubMed
Review: Webb MS, Saltman DL, Connors JM, Goldie JH. A literature review of single agent treatment of multiply relapsed aggressive non-Hodgkin's lymphoma. Leuk Lymphoma. 2002 May;43(5):975-82. link to original article PubMed
Oki Y, McLaughlin P, Pro B, Hagemeister FB, Bleyer A, Loyer E, Younes A. Phase II study of oxaliplatin in patients with recurrent or refractory non-Hodgkin lymphoma. Cancer. 2005 Aug 15;104(4):781-7. link to original article contains verified protocol PubMed
PIX301: Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. link to original article contains verified protocol PubMed
DLC-001: Czuczman MS, Trněný M, Davies A, Rule S, Linton KM, Wagner-Johnston N, Gascoyne RD, Slack GW, Brousset P, Eberhard DA, Hernandez-Ilizaliturri FJ, Salles G, Witzig TE, Zinzani PL, Wright GW, Staudt LM, Yang Y, Williams PM, Lih CJ, Russo J, Thakurta A, Hagner P, Fustier P, Song D, Lewis ID. A phase 2/3 multicenter, randomized, open-label study to compare the efficacy and safety of lenalidomide versus investigator's choice in patients with relapsed or refractory diffuse large B-cell lymphoma. Clin Cancer Res. 2017 Aug 1;23(15):4127-4137. Epub 2017 Apr 5. link to original article contains verified protocol in supplement PubMed

Panobinostat monotherapy

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Regimen

Study	Evidence	Comparator	Comparative Efficacy
Assouline et al. 2016 (Q-CROC-02)	Randomized Phase II (E-de-esc)	Panobinostat & Rituximab	Did not meet primary endpoint of ORR

Note: patients had a median of 2 prior treatments (range 1-8).

Chemotherapy

Panobinostat (Farydak) 30 mg PO three times per week (e.g., MWF)

21-day cycles

References

Q-CROC-02: Assouline SE, Nielsen TH, Yu S, Alcaide M, Chong L, MacDonald D, Tosikyan A, Kukreti V, Kezouh A, Petrogiannis-Haliotis T, Albuquerque M, Fornika D, Alamouti S, Froment R, Greenwood CM, Oros KK, Camglioglu E, Sharma A, Christodoulopoulos R, Rousseau C, Johnson N, Crump M, Morin RD, Mann KK. Phase 2 study of panobinostat with or without rituximab in relapsed diffuse large B-cell lymphoma. Blood. 2016 Jul 14;128(2):185-94. Epub 2016 May 10. link to original article contains verified protocol link to PMC article PubMed

Panobinostat & Rituximab

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Regimen

Study	Evidence	Comparator	Comparative Efficacy
Assouline et al. 2016 (Q-CROC-02)	Randomized Phase II, <20 pts (E-esc)	Panobinostat	Did not meet primary endpoint of ORR

Note: patients had a median of 3 prior treatments (range 2-9).

Chemotherapy

Panobinostat (Farydak) 30 mg PO three times per week (e.g., MWF)
Rituximab (Rituxan) 375 mg/m² IV once on day 1

21-day cycles

References

Q-CROC-02: Assouline SE, Nielsen TH, Yu S, Alcaide M, Chong L, MacDonald D, Tosikyan A, Kukreti V, Kezouh A, Petrogiannis-Haliotis T, Albuquerque M, Fornika D, Alamouti S, Froment R, Greenwood CM, Oros KK, Camglioglu E, Sharma A, Christodoulopoulos R, Rousseau C, Johnson N, Crump M, Morin RD, Mann KK. Phase 2 study of panobinostat with or without rituximab in relapsed diffuse large B-cell lymphoma. Blood. 2016 Jul 14;128(2):185-94. Epub 2016 May 10. link to original article contains verified protocol link to PMC article PubMed

Pixantrone monotherapy

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Regimen

Study	Evidence	Comparator	Comparative Efficacy
Pettengell et al. 2012 (PIX301)	Phase III (E-switch-ic)	Investigator's choice of: 1. Etoposide 2. Gemcitabine 3. Ifosfamide 4. Mitoxantrone 5. Oxaliplatin 6. Vinorelbine	Seems to have superior CR/CRu rate

Chemotherapy

Pixantrone (Pixuvri) 85 mg/m² IV once per day on days 1, 8, 15

28-day cycle for up to 6 cycles

References

PIX301: Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. link to original article contains verified protocol PubMed
1. Post-hoc analysis: Pettengell R, Sebban C, Zinzani PL, Derigs HG, Kravchenko S, Singer JW, Theocharous P, Wang L, Pavlyuk M, Makhloufi KM, Coiffier B. Monotherapy with pixantrone in histologically confirmed relapsed or refractory aggressive B-cell non-Hodgkin lymphoma: post-hoc analyses from a phase III trial. Br J Haematol. 2016 Sep;174(5):692-9. Epub 2016 Apr 26. link to original article link to PMC article PubMed

Rituximab monotherapy

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Regimen

Study	Evidence	Comparator	Comparative Efficacy
Coiffier et al. 1998	Randomized Phase II (E-de-esc)	Rituximab; higher-dose	Did not meet primary endpoint of ORR
Czuczman et al. 2017 (DLC-001)	Phase II/III (C)	Lenalidomide	Might have inferior ORR

Chemotherapy

Rituximab (Rituxan) as follows:
- Cycle 1: 375 mg/m² IV once per day on days 1, 8, 15, 22
- Cycles 4, 6, 8, 10: 375 mg/m² IV once on day 1

28-day cycle for 10 cycles (8 doses total)

References

Coiffier B, Haioun C, Ketterer N, Engert A, Tilly H, Ma D, Johnson P, Lister A, Feuring-Buske M, Radford JA, Capdeville R, Diehl V, Reyes F. Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: a multicenter phase II study. Blood. 1998 Sep 15;92(6):1927-32. link to original article PubMed
DLC-001: Czuczman MS, Trněný M, Davies A, Rule S, Linton KM, Wagner-Johnston N, Gascoyne RD, Slack GW, Brousset P, Eberhard DA, Hernandez-Ilizaliturri FJ, Salles G, Witzig TE, Zinzani PL, Wright GW, Staudt LM, Yang Y, Williams PM, Lih CJ, Russo J, Thakurta A, Hagner P, Fustier P, Song D, Lewis ID. A phase 2/3 multicenter, randomized, open-label study to compare the efficacy and safety of lenalidomide versus investigator's choice in patients with relapsed or refractory diffuse large B-cell lymphoma. Clin Cancer Res. 2017 Aug 1;23(15):4127-4137. Epub 2017 Apr 5. link to original article contains verified protocol in supplement PubMed

R-BL

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R-BL: Rituximab, Bendamustine, Lenalidomide

Regimen

Study	Evidence	Efficacy
Hitz et al. 2016 (SAKK 38/08)	Phase II	ORR: 61% (95% CI 45-76%)

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Bendamustine 70 mg/m² IV once per day on days 1 & 2
Lenalidomide (Revlimid) 10 mg PO once per day on days 1 to 21

28-day cycle for 6 cycles

References

Hitz F, Zucca E, Pabst T, Fischer N, Cairoli A, Samaras P, Caspar CB, Mach N, Krasniqi F, Schmidt A, Rothermundt C, Enoiu M, Eckhardt K, Berardi Vilei S, Rondeau S, Mey U. Rituximab, bendamustine and lenalidomide in patients with aggressive B-cell lymphoma not eligible for anthracycline-based therapy or intensive salvage chemotherapy - SAKK 38/08. Br J Haematol. 2016 Jul;174(2):255-63. Epub 2016 Mar 28. link to original article contains protocol PubMed

R-CVEP

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R-CVEP: Rituximab, Cyclophosphamide, Vorinostat, Etoposide, Prednisone

Regimen

Study	Evidence
Straus et al. 2014 (MSK 08-045)	Phase II

The MTD for vorinostat was 300 mg in this phase I/II trial.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 600 mg/m² IV once per day on days 1 & 8
Vorinostat (Zolinza) 300 mg PO once per day on days 1 to 10
Etoposide (Vepesid) 70 mg/m² IV once on day 1
Prednisone (Sterapred) 60 mg/m² PO once per day on days 1 to 10

28-day cycle for 6 cycles

References

MSK 08-045: Straus DJ, Hamlin PA, Matasar MJ, Lia Palomba M, Drullinsky PR, Zelenetz AD, Gerecitano JF, Noy A, Hamilton AM, Elstrom R, Wegner B, Wortman K, Cella D. Phase I/II trial of vorinostat with rituximab, cyclophosphamide, etoposide and prednisone as palliative treatment for elderly patients with relapsed or refractory diffuse large B-cell lymphoma not eligible for autologous stem cell transplantation. Br J Haematol. 2015 Mar;168(5):663-70. Epub 2014 Oct 15. link to original article contains protocol PubMed

R-GemOx

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R-GemOx: Rituximab, Gemcitabine, Oxaliplatin GEMOX-R: GEMcitabine, OXaliplatin, Rituximab

Regimen variant #1, 14-day cycles

Study	Evidence
El Gnaoui et al. 2007	Phase II
Mounier et al. 2013	Phase II

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Gemcitabine (Gemzar) 1000 mg/m² IV at fixed dose rate over 100 minutes once on day 2
Oxaliplatin (Eloxatin) 100 mg/m² IV over 2 hours once on day 2

Supportive medications

Methylprednisolone (Solumedrol) 1 mg/kg IV once on day 1, prior to Rituximab (Rituxan)
Acetaminophen (Tylenol) 1000 mg PO once on day 1, prior to Rituximab (Rituxan)
Dexchlorpheniramine (Polaramine) 6 mg PO once on day 1, prior to Rituximab (Rituxan)
Primary prophylaxis with G-CSF was not permitted

14-day cycle for up to 8 cycles

Regimen variant #2, 21-day cycles

Study	Evidence
López et al. 2008	Phase II

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Gemcitabine (Gemzar) 1000 mg/m² IV once on day 1
Oxaliplatin (Eloxatin) 100 mg/m² IV once on day 1

21-day cycle for 6 to 8 cycles

References

El Gnaoui T, Dupuis J, Belhadj K, Jais JP, Rahmouni A, Copie-Bergman C, Gaillard I, Diviné M, Tabah-Fisch I, Reyes F, Haioun C. Rituximab, gemcitabine and oxaliplatin: an effective salvage regimen for patients with relapsed or refractory B-cell lymphoma not candidates for high-dose therapy. Ann Oncol. 2007 Aug;18(8):1363-8. Epub 2007 May 11. link to original article contains verified protocol PubMed
López A, Gutiérrez A, Palacios A, Blancas I, Navarrete M, Morey M, Perelló A, Alarcón J, Martínez J, Rodríguez J. GEMOX-R regimen is a highly effective salvage regimen in patients with refractory/relapsing diffuse large-cell lymphoma: a phase II study. Eur J Haematol. 2008 Feb;80(2):127-32. Epub 2007 Nov 20. link to original article contains verified protocol PubMed
Mounier N, El-Gnaoui T, Tilly H, Canioni D, Sebban C, Casasnovas RO, Delarue R, Sonet A, Beaussart P, Petrella T, Castaigne S, Bologna S, Salles G, Rahmouni A, Gaulard P, Haioun C. Rituximab plus gemcitabine and oxaliplatin in refractory/relapsed patients with diffuse large B-cell lymphoma who are not candidates for high-dose therapy: a phase II Lymphoma Study Association trial. Haematologica. 2013 Nov;98(11):1726-31. Epub 2013 Jun 10. link to original article contains verified protocol link to PMC article PubMed

Temsirolimus monotherapy

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Regimen

Study	Evidence	Efficacy
Smith et al. 2010	Phase II	ORR: 28%

Chemotherapy

Temsirolimus (Torisel) 25 mg IV over 30 minutes once per day on days 1, 8, 15, 22

28-day cycle for up to 6 cycles

References

Smith SM, van Besien K, Karrison T, Dancey J, McLaughlin P, Younes A, Smith S, Stiff P, Lester E, Modi S, Doyle LA, Vokes EE, Pro B. Temsirolimus has activity in non-mantle cell non-Hodgkin's lymphoma subtypes: The University of Chicago phase II consortium. J Clin Oncol. 2010 Nov 1;28(31):4740-6. Epub 2010 Sep 13. link to original article contains verified protocol link to PMC article PubMed

Tisagenlecleucel monotherapy

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Regimen

FDA-recommended dose

Study	Years of enrollment	Evidence	Efficacy
Schuster et al. 2017 (UPCC 13413)		Phase II
Schuster et al. 2018 (JULIET)	2015-2017	Phase II (RT)	ORR: 59% (95% CI, 44-72)

The range given is the FDA-recommended dose used in JULIET.

Preceding treatment

Lymphodepleting therapy with FC or Bendamustine

Immunotherapy

Tisagenlecleucel (Kymriah) 0.6 to 6 x 10⁸ CTL019 transduced viable T-cells IV once on day 0

One course

References

UPCC 13413: Schuster SJ, Svoboda J, Chong EA, Nasta SD, Mato AR, Anak Ö, Brogdon JL, Pruteanu-Malinici I, Bhoj V, Landsburg D, Wasik M, Levine BL, Lacey SF, Melenhorst JJ, Porter DL, June CH. Chimeric Antigen Receptor T Cells in Refractory B-Cell Lymphomas. N Engl J Med. 2017 Dec 28;377(26):2545-2554. Epub 2017 Dec 10. link to original article link to PMC article PubMed
JULIET: Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, Jäger U, Jaglowski S, Andreadis C, Westin JR, Fleury I, Bachanova V, Foley SR, Ho PJ, Mielke S, Magenau JM, Holte H, Pantano S, Pacaud LB, Awasthi R, Chu J, Anak Ö, Salles G, Maziarz RT; JULIET Investigators. Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N Engl J Med. 2019 Jan 3;380(1):45-56. Epub 2018 Dec 1. link to original article PubMed

TTR

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TTR: Taxol (Paclitaxel), Topotecan, Rituximab

Regimen

Study	Evidence
Westin et al. 2014	Phase II

Chemotherapy

Paclitaxel (Taxol) 200 mg/m² IV once on day 2
Topotecan (Hycamtin) 1 mg/m² IV once per day on days 2 to 6
Rituximab (Rituxan) 375 mg/m² IV once on day 1

Supportive medications

Filgrastim (Neupogen) 5 mcg/kg SC once per day from day 7 until neutrophil recovery
Dexamethasone (Decadron) 20 mg IV once on day 2; 30 minutes prior to Paclitaxel (Taxol)
Diphenhydramine (Benadryl) 50 mg IV once on day 2; 30 minutes prior to Paclitaxel (Taxol)

21-day cycle for up to 6 cycles

References

Westin JR, McLaughlin P, Romaguera J, Hagemeister FB, Pro B, Dang NH, Samaniego F, Rodriguez MA, Fayad L, Oki Y, Fanale M, Fowler N, Nastoupil L, Feng L, Loyer E, Younes A. Paclitaxel, topotecan and rituximab: long term outcomes of an effective salvage programme for relapsed or refractory aggressive B-cell non-Hodgkin lymphoma. Br J Haematol. 2014 Oct;167(2):177-84. Epub 2014 Jul 8. link to original article contains verified protocol link to PMC article PubMed

Vinorelbine monotherapy

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Regimen

Study	Evidence	Comparator	Comparative Efficacy
Balzarotti et al. 1996	Non-randomized, <20 pts in this subgroup
Pettengell et al. 2012 (PIX301)	Phase III, <20 pts in this arm (C)	Pixantrone	Seems to have inferior CR/CRu rate

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.

Chemotherapy

Vinorelbine (Navelbine) 30 mg/m² IV once per day on days 1, 8, 15, 22

28-day cycle for up to 6 cycles

References

Balzarotti M, Santoro A, Tondini C, Fornier M, Bonadonna G. Activity of single agent vinorelbine in pretreated non-Hodgkin's lymphoma. Ann Oncol. 1996 Nov;7(9):970-2. link to original article contains verified protocol PubMed
Review: Webb MS, Saltman DL, Connors JM, Goldie JH. A literature review of single agent treatment of multiply relapsed aggressive non-Hodgkin's lymphoma. Leuk Lymphoma. 2002 May;43(5):975-82. link to original article PubMed
PIX301: Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. link to original article contains verified protocol PubMed
1. Post-hoc analysis: Pettengell R, Sebban C, Zinzani PL, Derigs HG, Kravchenko S, Singer JW, Theocharous P, Wang L, Pavlyuk M, Makhloufi KM, Coiffier B. Monotherapy with pixantrone in histologically confirmed relapsed or refractory aggressive B-cell non-Hodgkin lymphoma: post-hoc analyses from a phase III trial. Br J Haematol. 2016 Sep;174(5):692-9. Epub 2016 Apr 26. link to original article link to PMC article PubMed

Maintenance after further lines of therapy

Lenalidomide monotherapy

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Regimen

Study	Evidence
Zinzani et al. 2011a	Phase II

Preceding treatment

Lenalidomide & Rituximab x 4

Chemotherapy

Lenalidomide (Revlimid) 20 mg PO once per day on days 1 to 21

28-day cycle for 9 cycles

References

Zinzani PL, Pellegrini C, Gandolfi L, Stefoni V, Quirini F, Derenzini E, Broccoli A, Argnani L, Pileri S, Baccarani M. Combination of lenalidomide and rituximab in elderly patients with relapsed or refractory diffuse large B-cell lymphoma: a phase 2 trial. Clin Lymphoma Myeloma Leuk. 2011 Dec;11(6):462-6. Epub 2011 May 4. link to original article contains verified protocol PubMed
1. Update: Zinzani PL, Pellegrini C, Derenzini E, Argnani L, Pileri S. Long-term efficacy of the combination of lenalidomide and rituximab in elderly relapsed/refractory diffuse large B-cell lymphoma patients. Hematol Oncol. 2013 Dec;31(4):223-4. Epub 2013 Apr 26. link to original article PubMed

Response criteria

Prognosis

IPI and age-adjusted IPI (1993)

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To be completed

A predictive model for aggressive non-Hodgkin's lymphoma. The International Non-Hodgkin's Lymphoma Prognostic Factors Project. N Engl J Med. 1993 Sep 30;329(14):987-94. link to original article PubMed

Revised International Prognostic Index, R-IPI (2007)

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To be completed

Sehn LH, Berry B, Chhanabhai M, Fitzgerald C, Gill K, Hoskins P, Klasa R, Savage KJ, Shenkier T, Sutherland J, Gascoyne RD, Connors JM. The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood. 2007 Mar 1;109(5):1857-61. Epub 2006 Nov 14. link to original article PubMed

CNS-IPI (2016)

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Risk factors

Age greater than 60 years
Elevated LDH
ECOG PS greater than 1
Advanced stage (III or IV)
Involvement of more than one extranodal site
Involvement of the kidney and/or adrenal glands

Risk stratification

Low risk: 0 or 1 risk factors (2-year rate of CNS disease less than 5%)
Intermediate risk: 2 or 3 risk factors (2-year rate of CNS disease less than 5%)
High risk: 4 to 6 risk factors (2-year rate of CNS disease greater than 10%)

References

Schmitz N, Zeynalova S, Nickelsen M, Kansara R, Villa D, Sehn LH, Glass B, Scott DW, Gascoyne RD, Connors JM, Ziepert M, Pfreundschuh M, Loeffler M, Savage KJ. CNS International Prognostic Index: a risk model for CNS relapse in patients with diffuse large B-cell lymphoma treated with R-CHOP. J Clin Oncol. 2016 Sep 10;34(26):3150-3156. Epub 2016 Jul 5. link to original article PubMed

Investigational agents

These are drugs under study with at least some promising results for this disease.

@@ Line 1: / Line 1: @@
 {| class="wikitable" style="text-align:center; width:50%;"
-!colspan="2" align="center" style="color:white; font-size:125%; background-color:#de2d26"|'''Section editor'''
+! colspan="2" align="center" style="color:white; font-size:125%; background-color:#de2d26" |'''Section editor'''
 |-
-|style="background-color:#F0F0F0"|[[File:Jcvillasboas.jpg|frameless|upright=0.3|center]]
+| style="background-color:#F0F0F0" |[[File:Jcvillasboas.jpg|frameless|upright=0.3|center]]
 |<big>[[User:Jcvillasboas|J.C. Villasboas Bisneto, MD]]<br>Mayo Clinic<br>Rochester, MN</big>
 |-
@@ Line 18: / Line 18: @@
 =Guidelines=
 ==[http://www.esmo.org/ ESMO]==
 *'''2015:''' Tilly et al. [https://www.esmo.org/Guidelines/Haematological-Malignancies/Diffuse-Large-B-Cell-Lymphoma Diffuse large B-cell lymphoma (DLBCL): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
 ===Older===
 *'''2013:''' Ghielmini et al. [http://annonc.oxfordjournals.org/content/24/3/561.full.pdf+html ESMO Guidelines consensus conference on malignant lymphoma 2011 part 1: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL)] [https://www.ncbi.nlm.nih.gov/pubmed/23175624 PubMed]
 ==[https://www.nccn.org/ NCCN]==
 *[https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf NCCN Guidelines - B-cell Lymphomas]
@@ Line 34: / Line 38: @@
 ===Regimen variant #1, PO vincristine {{#subobject:561457|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(16)30171-5/fulltext Peyrade et al. 2016 (LYSA LNH09-7B)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Chemotherapy====
 *[[Vincristine (Oncovin)]] 1 mg PO once on day -7
 *[[Prednisone (Sterapred)]] 60 mg PO once per day on days -7 to -4
@@ Line 47: / Line 52: @@
 '''7-day course'''
 ====Subsequent treatment====
 *[[#O-miniCHOP|O-miniCHOP]]
 ===Regimen variant #2, IV vincristine {{#subobject:722d93|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://www.bloodjournal.org/content/104/3/626.long Pfreundschuh et al. 2004 (NHL-B1)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |[http://www.bloodjournal.org/content/104/3/634.long Pfreundschuh et al. 2004 (NHL-B2)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2808%2970002-0/fulltext Pfreundschuh et al. 2008 (RICOVER-60)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |[http://jco.ascopubs.org/content/32/36/4127.full Pfreundschuh et al. 2014 (SMARTE-R-CHOP-14)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''Recommended in '''NHL-B1''' and '''NHL-B2''' "to improve the performance status of patients and to ameliorate side-effects of the first chemotherapy cycle." Mandated in '''RICOVER-60''' and '''SMARTE-R-CHOP-14'''. Note: '''NHL-B1''' gave the option of a 5 to 7 day course of prednisone.''
 ====Chemotherapy====
 *[[Vincristine (Oncovin)]] 1 mg IV once (day not specified)
 *[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 7
@@ Line 74: / Line 81: @@
 '''7-day course'''
 ====Subsequent treatment====
 *NHL-B1 and NHL-B2: [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]] versus [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP-14|CHOP-14]] versus [[Diffuse_large_B-cell_lymphoma_-_historical#CHOEP-14|CHOEP-14]] versus [[Diffuse_large_B-cell_lymphoma_-_historical#CHOEP-21|CHOEP-21]]
 *RICOVER-60: [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP-14|CHOP-14]] versus [[#R-CHOP-14|R-CHOP-14]]
@@ Line 79: / Line 87: @@
 ===References===
-# '''NHL-B1:''' Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rudolph C, Reiser M, Hossfeld DK, Metzner B, Hasenclever D, Schmitz N, Glass B, Rübe C, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):626-33. Epub 2004 Feb 24. [http://www.bloodjournal.org/content/104/3/626.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14982884 PubMed]
-# '''NHL-B2:''' Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rübe C, Rudolph C, Reiser M, Hossfeld DK, Eimermacher H, Hasenclever D, Schmitz N, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):634-41. Epub 2004 Mar 11. [http://www.bloodjournal.org/content/104/3/634.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15016643 PubMed]
+#'''NHL-B1:''' Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rudolph C, Reiser M, Hossfeld DK, Metzner B, Hasenclever D, Schmitz N, Glass B, Rübe C, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):626-33. Epub 2004 Feb 24. [http://www.bloodjournal.org/content/104/3/626.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14982884 PubMed]
-# '''RICOVER-60:''' Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, Reiser M, Nickenig C, Clemens M, Peter N, Bokemeyer C, Eimermacher H, Ho A, Hoffmann M, Mertelsmann R, Trümper L, Balleisen L, Liersch R, Metzner B, Hartmann F, Glass B, Poeschel V, Schmitz N, Ruebe C, Feller AC, Loeffler M; German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 2008 Feb;9(2):105-16. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2808%2970002-0/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18226581 PubMed]
+#'''NHL-B2:''' Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rübe C, Rudolph C, Reiser M, Hossfeld DK, Eimermacher H, Hasenclever D, Schmitz N, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):634-41. Epub 2004 Mar 11. [http://www.bloodjournal.org/content/104/3/634.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15016643 PubMed]
-# '''SMARTE-R-CHOP-14:''' Pfreundschuh M, Poeschel V, Zeynalova S, Hänel M, Held G, Schmitz N, Viardot A, Dreyling MH, Hallek M, Mueller C, Wiesen MH, Witzens-Harig M, Truemper L, Keller U, Rixecker T, Zwick C, Murawski N. Optimization of rituximab for the treatment of diffuse large B-cell lymphoma (II): extended rituximab exposure time in the SMARTE-R-CHOP-14 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group. J Clin Oncol. 2014 Dec 20;32(36):4127-33. Epub 2014 Nov 17. Erratum in: J Clin Oncol. 2015 Jun 10;33(17):1991. [http://jco.ascopubs.org/content/32/36/4127.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25403207 PubMed]
+#'''RICOVER-60:''' Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, Reiser M, Nickenig C, Clemens M, Peter N, Bokemeyer C, Eimermacher H, Ho A, Hoffmann M, Mertelsmann R, Trümper L, Balleisen L, Liersch R, Metzner B, Hartmann F, Glass B, Poeschel V, Schmitz N, Ruebe C, Feller AC, Loeffler M; German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 2008 Feb;9(2):105-16. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2808%2970002-0/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18226581 PubMed]
-# '''LYSA LNH09-7B:''' Peyrade F, Bologna S, Delwail V, Emile JF, Pascal L, Fermé C, Schiano JM, Coiffier B, Corront B, Farhat H, Fruchart C, Ghesquieres H, Macro M, Tilly H, Choufi B, Delarue R, Fitoussi O, Gabarre J, Haioun C, Jardin F. Combination of ofatumumab and reduced-dose CHOP for diffuse large B-cell lymphomas in patients aged 80 years or older: an open-label, multicentre, single-arm, phase 2 trial from the LYSA group. Lancet Haematol. 2017 Jan;4(1):e46-e55. [https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(16)30171-5/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28041583 PubMed]
+#'''SMARTE-R-CHOP-14:''' Pfreundschuh M, Poeschel V, Zeynalova S, Hänel M, Held G, Schmitz N, Viardot A, Dreyling MH, Hallek M, Mueller C, Wiesen MH, Witzens-Harig M, Truemper L, Keller U, Rixecker T, Zwick C, Murawski N. Optimization of rituximab for the treatment of diffuse large B-cell lymphoma (II): extended rituximab exposure time in the SMARTE-R-CHOP-14 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group. J Clin Oncol. 2014 Dec 20;32(36):4127-33. Epub 2014 Nov 17. Erratum in: J Clin Oncol. 2015 Jun 10;33(17):1991. [http://jco.ascopubs.org/content/32/36/4127.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25403207 PubMed]
+#'''LYSA LNH09-7B:''' Peyrade F, Bologna S, Delwail V, Emile JF, Pascal L, Fermé C, Schiano JM, Coiffier B, Corront B, Farhat H, Fruchart C, Ghesquieres H, Macro M, Tilly H, Choufi B, Delarue R, Fitoussi O, Gabarre J, Haioun C, Jardin F. Combination of ofatumumab and reduced-dose CHOP for diffuse large B-cell lymphomas in patients aged 80 years or older: an open-label, multicentre, single-arm, phase 2 trial from the LYSA group. Lancet Haematol. 2017 Jan;4(1):e46-e55. [https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(16)30171-5/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28041583 PubMed]
 =Untreated, randomized data=
@@ Line 96: / Line 105: @@
 ===Regimen {{#subobject:1cd335|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-!style="width: 20%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
 |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61040-4/fulltext Récher et al. 2011 (LNH03-2B)]
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#1a9851" |Phase III (E-esc)
 |[[#R-CHOP|R-CHOP]]
-|style="background-color:#1a9850"|Superior OS
+| style="background-color:#1a9850" |Superior OS
-|style="background-color:#d73027"|Increased toxicity
+| style="background-color:#d73027" |Increased toxicity
 |-
 |[http://annonc.oxfordjournals.org/content/24/4/1032.long Ketterer et al. 2013 (LNH03-1B)]
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#1a9851" |Phase III (E-esc)
 |[[Diffuse_large_B-cell_lymphoma_-_historical#ACVBP|ACVBP]]
-|style="background-color:#91cf60"|Seems to have superior PFS
+| style="background-color:#91cf60" |Seems to have superior PFS
-|style="background-color:#eeee01"|Similar toxicity
+| style="background-color:#eeee01" |Similar toxicity
 |-
 |}
 ====Chemotherapy====
 *[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV once on day 1
@@ Line 124: / Line 134: @@
 ====CNS prophylaxis====
 *[[Methotrexate (MTX)]] 15 mg IT on day 1
 ====Supportive medications====
 *[[Filgrastim (Neupogen)]] 300 mcg (for patients less than 75 kg) or 480 mcg (for patients greater than or equal to 75 kg) SC once per day on days 6 to 13
 '''14-day cycle for 4 cycles'''
 ====Subsequent treatment====
 *[[#Methotrexate_monotherapy|Methotrexate consolidation]], in 4 weeks
 ===References===
-# '''LNH03-2B:''' Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, Thiéblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquières H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011 Nov 26;378(9806):1858-67. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61040-4/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22118442 PubMed]
-## '''Subgroup analysis:''' Molina TJ, Canioni D, Copie-Bergman C, Recher C, Brière J, Haioun C, Berger F, Fermé C, Copin MC, Casasnovas O, Thieblemont C, Petrella T, Leroy K, Salles G, Fabiani B, Morschauser F, Mounier N, Coiffier B, Jardin F, Gaulard P, Jais JP, Tilly H. Young patients with non-germinal center B-cell-like diffuse large B-cell lymphoma benefit from intensified chemotherapy with ACVBP plus rituximab compared with CHOP plus rituximab: analysis of data from the Groupe d'Etudes des Lymphomes de l'Adulte/lymphoma study association phase III trial LNH 03-2B. J Clin Oncol. 2014 Dec 10;32(35):3996-4003. Epub 2014 Nov 10. [https://ascopubs.org/doi/full/10.1200/JCO.2013.54.9493 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25385729 PubMed]
+#'''LNH03-2B:''' Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, Thiéblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquières H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011 Nov 26;378(9806):1858-67. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61040-4/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22118442 PubMed]
-# '''LNH03-1B:''' Ketterer N, Coiffier B, Thieblemont C, Fermé C, Brière J, Casasnovas O, Bologna S, Christian B, Connerotte T, Récher C, Bordessoule D, Fruchart C, Delarue R, Bonnet C, Morschhauser F, Anglaret B, Soussain C, Fabiani B, Tilly H, Haioun C. Phase III study of ACVBP versus ACVBP plus rituximab for patients with localized low-risk diffuse large B-cell lymphoma (LNH03-1B). Ann Oncol. 2013 Apr;24(4):1032-7. Epub 2012 Dec 12. [http://annonc.oxfordjournals.org/content/24/4/1032.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23235801 PubMed]
+##'''Subgroup analysis:''' Molina TJ, Canioni D, Copie-Bergman C, Recher C, Brière J, Haioun C, Berger F, Fermé C, Copin MC, Casasnovas O, Thieblemont C, Petrella T, Leroy K, Salles G, Fabiani B, Morschauser F, Mounier N, Coiffier B, Jardin F, Gaulard P, Jais JP, Tilly H. Young patients with non-germinal center B-cell-like diffuse large B-cell lymphoma benefit from intensified chemotherapy with ACVBP plus rituximab compared with CHOP plus rituximab: analysis of data from the Groupe d'Etudes des Lymphomes de l'Adulte/lymphoma study association phase III trial LNH 03-2B. J Clin Oncol. 2014 Dec 10;32(35):3996-4003. Epub 2014 Nov 10. [https://ascopubs.org/doi/full/10.1200/JCO.2013.54.9493 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25385729 PubMed]
+#'''LNH03-1B:''' Ketterer N, Coiffier B, Thieblemont C, Fermé C, Brière J, Casasnovas O, Bologna S, Christian B, Connerotte T, Récher C, Bordessoule D, Fruchart C, Delarue R, Bonnet C, Morschhauser F, Anglaret B, Soussain C, Fabiani B, Tilly H, Haioun C. Phase III study of ACVBP versus ACVBP plus rituximab for patients with localized low-risk diffuse large B-cell lymphoma (LNH03-1B). Ann Oncol. 2013 Apr;24(4):1032-7. Epub 2012 Dec 12. [http://annonc.oxfordjournals.org/content/24/4/1032.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23235801 PubMed]
 ==DA-R-EPOCH {{#subobject:ba36e5|Regimen=1}}==
@@ Line 147: / Line 161: @@
 ===Regimen {{#subobject:6c5478|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-!style="width: 20%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2006.06438.x/full García-Suárez et al. 2007]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409217/ Wilson et al. 2008]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342980/ Wilson et al. 2011 (CALGB 50103)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/bjh.13273/full Purroy et al. 2014]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774813/ Bartlett et al. 2019 (CALGB 50303)]
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#1a9851" |Phase III (E-esc)
 |[[#R-CHOP|R-CHOP]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of EFS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
-|style="background-color:#d73027"|Increased toxicity
+| style="background-color:#d73027" |Increased toxicity
 |-
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per cycle or day 1 before the start of EPOCH (depending on reference)
 *[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 200 mg/m<sup>2</sup>)
 *[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO twice per day on days 1 to 5
 *[[Vincristine (Oncovin)]] 0.4 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg/m<sup>2</sup>)
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV over 15 minutes once on day 5
 *[[Doxorubicin (Adriamycin)]] 10 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m<sup>2</sup>)
 ====Supportive medications====
 *Growth factor support with one of the following:
 **[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 6 and continuing until ANC greater than 5000/uL past nadir
@@ Line 199: / Line 215: @@
 **[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO twice per day 3 days per week
 ***Alternative used only in García-Suárez et al. 2007: cotrimoxazole 480 mg PO twice per day 3 days per week
 **[[Atovaquone (Mepron)]] 1500 mg PO once per day
 **[[Pentamidine (Nebupent)]] 300 mg nebulized every 28 days
 *Only in García-Suárez et al. 2007: [[Darbepoetin alfa (Aranesp)]] 2.25 mcg/kg SC when hemoglobin concentration was less than or equal to 10 g/dL.
@@ Line 206: / Line 222: @@
 ====Dose modifications====
 *Start cycle 1 as described above.
 *Obtain CBCs twice per week for nadir measurements.
@@ Line 216: / Line 233: @@
 ===References===
-# García-Suárez J, Bañas H, Arribas I, De Miguel D, Pascual T, Burgaleta C. Dose-adjusted EPOCH plus rituximab is an effective regimen in patients with poor-prognostic untreated diffuse large B-cell lymphoma: results from a prospective observational study. Br J Haematol. 2007 Jan;136(2):276-85. [https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2006.06438.x/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17233819 PubMed]
-# Wilson WH, Dunleavy K, Pittaluga S, Hegde U, Grant N, Steinberg SM, Raffeld M, Gutierrez M, Chabner BA, Staudt L, Jaffe ES, Janik JE. Phase II study of dose-adjusted EPOCH and rituximab in untreated diffuse large B-cell lymphoma with analysis of germinal center and post-germinal center biomarkers. J Clin Oncol. 2008 Jun 1;26(16):2717-24. [http://jco.ascopubs.org/content/26/16/2717.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409217/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18378569 PubMed]
+#García-Suárez J, Bañas H, Arribas I, De Miguel D, Pascual T, Burgaleta C. Dose-adjusted EPOCH plus rituximab is an effective regimen in patients with poor-prognostic untreated diffuse large B-cell lymphoma: results from a prospective observational study. Br J Haematol. 2007 Jan;136(2):276-85. [https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2006.06438.x/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17233819 PubMed]
-# '''CALGB 50103:''' Wilson WH, Jung SH, Porcu P, Hurd D, Johnson J, Martin SE, Czuczman M, Lai R, Said J, Chadburn A, Jones D, Dunleavy K, Canellos G, Zelenetz AD, Cheson BD, Hsi ED; Cancer Leukemia Group B. A Cancer and Leukemia Group B multi-center study of DA-EPOCH-rituximab in untreated diffuse large B-cell lymphoma with analysis of outcome by molecular subtype. Haematologica. 2012 May;97(5):758-65. Epub 2011 Dec 1. [http://www.haematologica.org/content/97/5/758.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342980/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22133772 PubMed]
+#Wilson WH, Dunleavy K, Pittaluga S, Hegde U, Grant N, Steinberg SM, Raffeld M, Gutierrez M, Chabner BA, Staudt L, Jaffe ES, Janik JE. Phase II study of dose-adjusted EPOCH and rituximab in untreated diffuse large B-cell lymphoma with analysis of germinal center and post-germinal center biomarkers. J Clin Oncol. 2008 Jun 1;26(16):2717-24. [http://jco.ascopubs.org/content/26/16/2717.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409217/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18378569 PubMed]
+#'''CALGB 50103:''' Wilson WH, Jung SH, Porcu P, Hurd D, Johnson J, Martin SE, Czuczman M, Lai R, Said J, Chadburn A, Jones D, Dunleavy K, Canellos G, Zelenetz AD, Cheson BD, Hsi ED; Cancer Leukemia Group B. A Cancer and Leukemia Group B multi-center study of DA-EPOCH-rituximab in untreated diffuse large B-cell lymphoma with analysis of outcome by molecular subtype. Haematologica. 2012 May;97(5):758-65. Epub 2011 Dec 1. [http://www.haematologica.org/content/97/5/758.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342980/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22133772 PubMed]
 <!-- previously presented in part at the 51st Annual Meeting of the American Society of Hematology, New Orleans, LA, December 5-8, 2009, and the 53rd Annual Meeting of the American Society of Hematology, San Diego, CA, December 10-13, 2011. -->
-# Purroy N, Bergua J, Gallur L, Prieto J, Lopez LA, Sancho JM, García-Marco JA, Castellví J, Montes-Moreno S, Batlle A, de Villambrosia SG, Carnicero F, Ferrando-Lamana L, Piris MA, Lopez A. Long-term follow-up of dose-adjusted EPOCH plus rituximab (DA-EPOCH-R) in untreated patients with poor prognosis large B-cell lymphoma: a phase II study conducted by the Spanish PETHEMA group. Br J Haematol. 2015 Apr;169(2):188-98. Epub 2014 Dec 18. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13273/full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25521006 PubMed]
+#Purroy N, Bergua J, Gallur L, Prieto J, Lopez LA, Sancho JM, García-Marco JA, Castellví J, Montes-Moreno S, Batlle A, de Villambrosia SG, Carnicero F, Ferrando-Lamana L, Piris MA, Lopez A. Long-term follow-up of dose-adjusted EPOCH plus rituximab (DA-EPOCH-R) in untreated patients with poor prognosis large B-cell lymphoma: a phase II study conducted by the Spanish PETHEMA group. Br J Haematol. 2015 Apr;169(2):188-98. Epub 2014 Dec 18. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13273/full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25521006 PubMed]
 <!-- Prior publication: Poster presentation at the 2014 annual meeting of the American Society of Hematology (Howlett C, Landsburg DJ, Chong EA, Snedecor SJ, Schuster SJ, Green TM, Cohen JB, Svoboda J, Nasta SD, Feldman T, Rago R, Land D, Walsh KM, Goy A, Mato AR. Front-line, dose-escalated immunochemotherapy is associated with a significant PFS (but not OS) advantage in 401 patients (pts) with double-hit lymphomas (DHL): A systematic review and meta-analysis. Blood, 124, abst 3056). -->
-# '''Retrospective:''' Howlett C, Snedecor SJ, Landsburg DJ, Svoboda J, Chong EA, Schuster SJ, Nasta SD, Feldman T, Rago A, Walsh KM, Weber S, Goy A, Mato A. Front-line, dose-escalated immunochemotherapy is associated with a significant progression-free survival advantage in patients with double-hit lymphomas: a systematic review and meta-analysis. Br J Haematol. 2015 Aug;170(4):504-14. Epub 2015 Apr 24. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13463/full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25907897 PubMed]
+#'''Retrospective:''' Howlett C, Snedecor SJ, Landsburg DJ, Svoboda J, Chong EA, Schuster SJ, Nasta SD, Feldman T, Rago A, Walsh KM, Weber S, Goy A, Mato A. Front-line, dose-escalated immunochemotherapy is associated with a significant progression-free survival advantage in patients with double-hit lymphomas: a systematic review and meta-analysis. Br J Haematol. 2015 Aug;170(4):504-14. Epub 2015 Apr 24. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13463/full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25907897 PubMed]
 <!-- # '''Abstract:''' Wyndham H. Wilson, MD, PhD, Jung sin-Ho, Brandelyn Nicole Pitcher, MS, Eric D Hsi, MD, Jonathan Friedberg, MD, Bruce Cheson, MD, Nancy L Bartlett, MD, Scott Smith, Nina Wagner Johnston, MD, Brad S Kahl, Louis M. Staudt, MD, PhD, Kristie Blum, MD, Jeremy Abramson, Oliver W Press, MD, PhD, Richard I. Fisher, MD, Kristy L. Richards, PhD, MD, Heiko Schoder, MD, Julie E Chang, Andrew D. Zelenetz and John P. Leonard, MD. Phase III Randomized Study of R-CHOP Versus DA-EPOCH-R and Molecular Analysis of Untreated Diffuse Large B-Cell Lymphoma: CALGB/Alliance 50303. ASH 2016 Abstract 469 [https://ashpublications.org/blood/article/128/22/469/101297/Phase-III-Randomized-Study-of-R-CHOP-Versus-DA link to abstract] -->
-# '''CALGB 50303:''' Bartlett NL, Wilson WH, Jung SH, Hsi ED, Maurer MJ, Pederson LD, Polley MC, Pitcher BN, Cheson BD, Kahl BS, Friedberg JW, Staudt LM, Wagner-Johnston ND, Blum KA, Abramson JS, Reddy NM, Winter JN, Chang JE, Gopal AK, Chadburn A, Mathew S, Fisher RI, Richards KL, Schöder H, Zelenetz AD, Leonard JP. Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303. J Clin Oncol. 2019 Jul 20;37(21):1790-1799. Epub 2019 Apr 2. [https://ascopubs.org/doi/full/10.1200/JCO.18.01994 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774813/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/30939090 PubMed]
+#'''CALGB 50303:''' Bartlett NL, Wilson WH, Jung SH, Hsi ED, Maurer MJ, Pederson LD, Polley MC, Pitcher BN, Cheson BD, Kahl BS, Friedberg JW, Staudt LM, Wagner-Johnston ND, Blum KA, Abramson JS, Reddy NM, Winter JN, Chang JE, Gopal AK, Chadburn A, Mathew S, Fisher RI, Richards KL, Schöder H, Zelenetz AD, Leonard JP. Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303. J Clin Oncol. 2019 Jul 20;37(21):1790-1799. Epub 2019 Apr 2. [https://ascopubs.org/doi/full/10.1200/JCO.18.01994 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774813/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/30939090 PubMed]
 ==R-CHOEP-14 {{#subobject:75c24e|Regimen=1}}==
@@ Line 235: / Line 253: @@
 ===Regimen variant #1, flat-dose vincristine {{#subobject:b156e5|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-!style="width: 20%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
 |[https://link.springer.com/article/10.1385%2FMO%3A23%3A2%3A283 Adde et al. 2006]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 | style="background-color:#d3d3d3" |
 | style="background-color:#d3d3d3" |
@@ Line 248: / Line 266: @@
 |-
 |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70481-3/fulltext Schmitz et al. 2012 (DSHNHL 2002-1)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |R-MegaCHOEP
-|style="background-color:#ffffbf"|Did not meet primary endpoint of EFS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
-|style="background-color:#1a9851"|Decreased toxicity
+| style="background-color:#1a9851" |Decreased toxicity
 |-
 |}
 ''Note: to our knowledge, this regimen was not tested as an experimental arm in a RCT prior to becoming a standard comparator arm.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] as follows:
 **Cycles 1 to 4, 6, 8: 375 mg/m<sup>2</sup> IV once on day 0
@@ Line 266: / Line 285: @@
 '''14-day cycle for 8 cycles'''
 ====Subsequent treatment====
 *"Mandatory" for patients with bulky disease (any mass greater than 7.5cm in diameter, or extranodal involvement): [[#Radiation_therapy|RT]] x 36 Gy
 ===Regimen variant #2, capped vincristine, with CNS prophylaxis {{#subobject:0258f4|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://annonc.oxfordjournals.org/content/24/5/1385.long Holte et al. 2012 (NLG LBC-04)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''Note: Consolidative radiotherapy "given at the discretion of the individual centers (36 to 45 Gy). Indications for giving radiotherapy after the completion of chemotherapy included bulky disease (greater than or equal to 10 cm) at diagnosis, localized PET-positive residual lesions, and residual disease, not eligible for biopsy at a localized site, and potentially curable by radiotherapy."''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 287: / Line 308: @@
 ====Supportive medications====
 *ONE of the following:
 **[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day from day 4
@@ Line 293: / Line 315: @@
 '''14-day cycle for 8 cycles'''
 ====Subsequent treatment====
 *CNS prophylaxis: [[CNS_lymphoma#Cytarabine_monotherapy|HiDAC]], then [[CNS_lymphoma#Methotrexate_monotherapy|HD-MTX]]
 ===References===
-# Adde M, Enblad G, Hagberg H, Sundström C, Laurell A. Outcome for young high-risk aggressive B-cell lymphoma patients treated with CHOEP-14 and rituximab (R-CHOEP-14). Med Oncol. 2006;23(2):283-93. [https://link.springer.com/article/10.1385%2FMO%3A23%3A2%3A283 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16720929 PubMed]
-# '''DSHNHL 2002-1:''' Schmitz N, Nickelsen M, Ziepert M, Haenel M, Borchmann P, Schmidt C, Viardot A, Bentz M, Peter N, Ehninger G, Doelken G, Ruebe C, Truemper L, Rosenwald A, Pfreundschuh M, Loeffler M, Glass B; for the German High-Grade Lymphoma Study Group (DSHNHL). Conventional chemotherapy (CHOEP-14) with rituximab or high-dose chemotherapy (MegaCHOEP) with rituximab for young, high-risk patients with aggressive B-cell lymphoma: an open-label, randomised, phase 3 trial (DSHNHL 2002-1). Lancet Oncol. 2012 Dec;13(12):1250-1259. Epub 2012 Nov 16. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70481-3/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23168367 PubMed]
+#Adde M, Enblad G, Hagberg H, Sundström C, Laurell A. Outcome for young high-risk aggressive B-cell lymphoma patients treated with CHOEP-14 and rituximab (R-CHOEP-14). Med Oncol. 2006;23(2):283-93. [https://link.springer.com/article/10.1385%2FMO%3A23%3A2%3A283 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16720929 PubMed]
-# '''NLG LBC-04:''' Holte H, Leppä S, Björkholm M, Fluge O, Jyrkkiö S, Delabie J, Sundström C, Karjalainen-Lindsberg ML, Erlanson M, Kolstad A, Fosså A, Ostenstad B, Löfvenberg E, Nordström M, Janes R, Pedersen LM, Anderson H, Jerkeman M, Eriksson M. Dose-densified chemoimmunotherapy followed by systemic central nervous system prophylaxis for younger high-risk diffuse large B-cell/follicular grade 3 lymphoma patients: results of a phase II Nordic Lymphoma Group study. Ann Oncol. 2013 May;24(5):1385-92. Epub 2012 Dec 17. [http://annonc.oxfordjournals.org/content/24/5/1385.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23247661 PubMed]
+#'''DSHNHL 2002-1:''' Schmitz N, Nickelsen M, Ziepert M, Haenel M, Borchmann P, Schmidt C, Viardot A, Bentz M, Peter N, Ehninger G, Doelken G, Ruebe C, Truemper L, Rosenwald A, Pfreundschuh M, Loeffler M, Glass B; for the German High-Grade Lymphoma Study Group (DSHNHL). Conventional chemotherapy (CHOEP-14) with rituximab or high-dose chemotherapy (MegaCHOEP) with rituximab for young, high-risk patients with aggressive B-cell lymphoma: an open-label, randomised, phase 3 trial (DSHNHL 2002-1). Lancet Oncol. 2012 Dec;13(12):1250-1259. Epub 2012 Nov 16. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70481-3/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23168367 PubMed]
+#'''NLG LBC-04:''' Holte H, Leppä S, Björkholm M, Fluge O, Jyrkkiö S, Delabie J, Sundström C, Karjalainen-Lindsberg ML, Erlanson M, Kolstad A, Fosså A, Ostenstad B, Löfvenberg E, Nordström M, Janes R, Pedersen LM, Anderson H, Jerkeman M, Eriksson M. Dose-densified chemoimmunotherapy followed by systemic central nervous system prophylaxis for younger high-risk diffuse large B-cell/follicular grade 3 lymphoma patients: results of a phase II Nordic Lymphoma Group study. Ann Oncol. 2013 May;24(5):1385-92. Epub 2012 Dec 17. [http://annonc.oxfordjournals.org/content/24/5/1385.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23247661 PubMed]
 ==R-CHOP {{#subobject:240cc2|Regimen=1}}==
@@ Line 311: / Line 335: @@
 <br>CHOPR: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone, '''<u>R</u>'''ituximab
 ===Example orders===
 *[[Example orders for R-CHOP in lymphoma]]
@@ Line 317: / Line 342: @@
 ===Regimen variant #1, prednisone 40 mg/m<sup>2</sup> {{#subobject:a326e|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.nejm.org/doi/full/10.1056/NEJMoa011795 Coiffier et al. 2002 (LNH 98-5)]
 |1998-2000
-|style="background-color:#1a9851"|Phase III (E-RT-esc)
+| style="background-color:#1a9851" |Phase III (E-RT-esc)
 |[[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]]
-|style="background-color:#1a9850"|Superior OS
+| style="background-color:#1a9850" |Superior OS
 |-
 |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70122-0/fulltext Delarue et al. 2013 (LNH03-6B)]
 |{{#subobject:xx|ToDo=1}}
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#R-CHOP-14|R-CHOP-14]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of EFS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 |-
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 344: / Line 370: @@
 ====Supportive medications====
 *[[Filgrastim (Neupogen)]] used for later cycles if patients developed grade 4 neutropenia or febrile neutropenia
@@ Line 350: / Line 377: @@
 ====CNS prophylaxis====
 As described in Delarue et al. 2013 (LNH03-6B):
 *[[Methotrexate (MTX)]] 15 mg IT once on day 1
@@ Line 356: / Line 384: @@
 ===Regimen variant #2, prednisone 60 mg/m<sup>2</sup> {{#subobject:18b582|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-!style="width: 20%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
 |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61040-4/fulltext Récher et al. 2011 (LNH03-2B)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#ACVBP-R|ACVBP-R]]
-|style="background-color:#d73027"|Inferior OS
+| style="background-color:#d73027" |Inferior OS
-|style="background-color:#1a9851"|Decreased toxicity
+| style="background-color:#1a9851" |Decreased toxicity
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639223/ Li et al. 2018 (CSWOG0001)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#R-CHOP-14|R-CHOP-14]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
@@ Line 376: / Line 404: @@
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 386: / Line 415: @@
 ===Regimen variant #3, prednisone 100 mg, capped vincristine, 4 cycles {{#subobject:13e2ib|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-!style="width: 20%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
 |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)33008-9/fulltext Poeschel et al. 2019 (FLYER)]
-|style="background-color:#1a9851"|Phase III (E-de-esc)
+| style="background-color:#1a9851" |Phase III (E-de-esc)
 |[[#R-CHOP|R-CHOP]] x 6
-|style="background-color:#eeee01"|Non-inferior PFS36
+| style="background-color:#eeee01" |Non-inferior PFS36
 | style="background-color:#1a9850" |Less toxic
 |-
@@ Line 401: / Line 430: @@
 ''Note: Patients in FLYER were 18 to 60 and had no risk factors according to age-adjusted IPI.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] as follows:
@@ Line 415: / Line 445: @@
 ===Regimen variant #4, prednisone 100 mg, capped vincristine, 6 cycles {{#subobject:13e254|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-!style="width: 20%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
 |[https://ascopubs.org/doi/full/10.1200/JCO.2001.19.2.389 Vose et al. 2001]
@@ Line 428: / Line 458: @@
 |-
 |[https://www.tandfonline.com/doi/full/10.3109/10428194.2011.621565 Merli et al. 2012 (ANZINTER3)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#R-miniCEOP|R-miniCEOP]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of EFS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 |
 |-
 |[https://academic.oup.com/annonc/article/24/10/2618/177246 Herbrecht et al. 2013 (PIX203)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |CPOP-R
-|style="background-color:#ffffbf"|Inconclusive whether non-inferior CR/CRu rate (*)
+| style="background-color:#ffffbf" |Inconclusive whether non-inferior CR/CRu rate (*)
 |
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278952/ Oki et al. 2013 (MDACC 2005-0054)]
-|style="background-color:#1a9851"|Randomized Phase II (C)
+| style="background-color:#1a9851" |Randomized Phase II (C)
 |[[#R-Hyper-CVAD.2FR-MA|R-Hyper-CVAD/R-MA]]
-|style="background-color:#fc8d59"|Seems to have inferior CRR
+| style="background-color:#fc8d59" |Seems to have inferior CRR
 |
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116833/ Seymour et al. 2014 (MAIN)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |RA-CHOP-21
-|style="background-color:#ffffbf"|Did not meet secondary endpoint of PFS
+| style="background-color:#ffffbf" |Did not meet secondary endpoint of PFS
 | style="background-color:#1a9850" |Better cardiac safety
 |-
 |[https://ascopubs.org/doi/full/10.1200/JCO.2017.73.3402 Vitolo et al. 2017 (GOYA)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |G-CHOP
-|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 |
 |-
 |[https://ascopubs.org/doi/full/10.1200/JCO.2017.73.2784 Leonard et al. 2017 (C05013)]
-|style="background-color:#1a9851"|Randomized Phase II (C)
+| style="background-color:#1a9851" |Randomized Phase II (C)
 |[[Diffuse_large_B-cell_lymphoma_-_historical#VR-CHOP|VR-CHOP]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 |
 |-
 |[https://onlinelibrary.wiley.com/doi/abs/10.1002/hon.2524 Hara et al. 2018]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |R-THP-CHOP
-|style="background-color:#eeee01"|Non-inferior CR rate
+| style="background-color:#eeee01" |Non-inferior CR rate
 |
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6553835/ Younes et al. 2019 (PHOENIX)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |IR-CHOP
-|style="background-color:#ffffbf"|Did not meet primary endpoint of EFS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 |
 |-
 |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)33008-9/fulltext Poeschel et al. 2019 (FLYER)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#R-CHOP|R-CHOP]] x 4
-|style="background-color:#eeee01"|Non-inferior PFS36
+| style="background-color:#eeee01" |Non-inferior PFS36
 | style="background-color:#d73027" |More toxic
 |-
@@ Line 484: / Line 514: @@
 ''Note: patients in Vose et al. 2001 received rituximab 2 days before CHOP, i.e., all CHOP days are moved forward by 2 days. Patients in GOYA received 8 doses of rituximab, regardless of the number of chemotherapy cycles given. While the primary endpoing in PIX203 was inconclusive (non-inferiority by CR/CRu rate), this arm seemed to have superior OS. Hara et al. 2018 does not have dosing information available in the abstract. Patients in FLYER were 18 to 60 and had no risk factors according to age-adjusted IPI.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 491: / Line 522: @@
 ====Supportive medications====
 *Varies per protocol
 *Prophylactic [[:Category:Granulocyte colony-stimulating factors|G-CSF]] used for persisting grade 4 neutropenia or febrile neutropenia.
@@ Line 498: / Line 530: @@
 '''21-day cycle for 6 to 8 cycles (see note)'''
 ====Subsequent treatment====
 *Some protocols: [[#Radiation_therapy|Radiation therapy]] was scheduled for sites of previous bulky disease or partially responding sites
 ===Regimen variant #5, prednisone 100 mg, flat-dose vincristine {{#subobject:bcb2bf|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-!style="width: 20%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
 |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2806%2970664-7/fulltext Pfreundschuh et al. 2006 (NCIC CTG LY.9)]
-|style="background-color:#1a9851"|Phase III (E-RT-esc)
+| style="background-color:#1a9851" |Phase III (E-RT-esc)
 |1. [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]]<br> 2. [[Diffuse_large_B-cell_lymphoma_-_historical#CHOEP-21|CHOEP-21]]<br> 3. [[Diffuse_large_B-cell_lymphoma_-_historical#MACOP-B|MACOP-B]]<br> 4. [[Diffuse_large_B-cell_lymphoma_-_historical#PMitCEBO|PMitCEBO]]
-|style="background-color:#1a9850"|Superior EFS
+| style="background-color:#1a9850" |Superior EFS
-|style="background-color:#eeee01"|Similar toxicity
+| style="background-color:#eeee01" |Similar toxicity
 |-
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 523: / Line 557: @@
 ====Supportive medications====
 *G-CSF with one of the following:
 **[[Filgrastim (Neupogen)]] used at physician discretion for neutropenia
@@ Line 530: / Line 565: @@
 ====Subsequent treatment====
 *[[#Radiation_therapy|Radiation therapy]] 30 to 40 Gy given to sites of primary bulky disease; 30 to 40 Gy to primary extranodal disease at physician discretion
 ===Regimen variant #6, prednisone 100 mg/m<sup>2</sup> {{#subobject:e3dfe2|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616024/ Offner et al. 2015 (LYM-2034)]
-|style="background-color:#1a9851"|Randomized Phase II (C)
+| style="background-color:#1a9851" |Randomized Phase II (C)
 |VR-CAP
-|style="background-color:#ffffbf"|Did not meet primary endpoint of CR rate
+| style="background-color:#ffffbf" |Did not meet primary endpoint of CR rate
 |-
 |}
 ''This regimen was used for non-germinal center B-cell (non-GCB) DLBCL.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 557: / Line 594: @@
 ===Regimen variant #7, rituximab lead-in {{#subobject:f05383|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://jco.ascopubs.org/content/24/19/3121.long Habermann et al. 2006 (ECOG E4494/CALGB 9793)]
 |1998-2001
-|style="background-color:#1a9851"|Phase III (E-RT-esc)
+| style="background-color:#1a9851" |Phase III (E-RT-esc)
 |[[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]]
-|style="background-color:#91cf60"|Seems to have superior FFS
+| style="background-color:#91cf60" |Seems to have superior FFS
 |-
 |}
 ''Note: an advantage for maintenance was only seen in the group receiving [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]] upfront, which is no longer standard of care.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] as follows:
 **Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days -7 & -3
 **Cycle 2 onwards: 375 mg/m<sup>2</sup> IV once on day -2
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 581: / Line 619: @@
 ====Supportive medications====
 *Recommended: [[Filgrastim (Neupogen)]] "according to guidelines"
 '''21-day cycle for 6 to 8 cycles'''
 ====Subsequent treatment====
 *[[#Rituximab_monotherapy|Rituximab maintenance]] versus [[#Observation|observation]]
 ===Regimen variant #8, short-course for early stage DLBCL {{#subobject:caca45|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://jco.ascopubs.org/content/26/14/2258.long Persky et al. 2008 (SWOG S0014)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355104/ Yoon et al. 2017 (CISL 12-09)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''Note: CISL 12-09 does not have dosing details.''
 ====Preceding treatment====
 *CISL 12-09: [[Surgery#Surgical_resection|Surgical resection]]
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] as follows:
 **Prephase: 375 mg/m<sup>2</sup> IV once on day -7
@@ Line 614: / Line 657: @@
 ====Subsequent treatment====
 *SWOG S0014: [[#Radiation_therapy|IFRT]] to begin 3 weeks after last cycle of R-CHOP
 ===Regimen variant #9, primary testicular DLBCL {{#subobject:7f4db5|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://jco.ascopubs.org/content/29/20/2766.long Vitolo et al. 2011 (IELSG-10)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''This regimen is for primary testicular lymphoma, and is a component of a sequential treatment protocol.''
 ====Preceding treatment====
 *Diagnostic [[Surgery#Orchiectomy|orchiectomy]] prior to starting chemotherapy
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 0 or 1
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 637: / Line 684: @@
 '''21-day cycle for 6 cycles (up to 8 cycles for stage II patients)'''
 ====CNS prophylaxis====
 *[[Methotrexate (MTX)]] 12 mg IT once per day on days 1, 8, 15, 22
 '''4-week course'''
 ====Subsequent treatent====
 *[[#Radiation_therapy|RT]]
 ===Regimen variant #10, 2 cycles with response adaptation {{#subobject:d56c17|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691189/ Witzig et al. 2015 (ECOG E3402)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''This regimen is intended for stage I-II DLBCL based on CT (not PET-CT) imaging.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 662: / Line 712: @@
 '''21-day cycle for 2 cycles'''
 ====Subsequent treatment====
 *CR based on '''CT''' scan: R-CHOP x 2 (4 cycles total), then [[#Ibritumomab_tiuxetan_monotherapy|ibritumomab tiuxetan consolidation]]
 *CRu or PR based on '''CT''' scan: R-CHOP x 4 (6 cycles total), then [[#Ibritumomab_tiuxetan_monotherapy|ibritumomab tiuxetan consolidation]]
 ===References===
-# Vose JM, Link BK, Grossbard ML, Czuczman M, Grillo-Lopez A, Gilman P, Lowe A, Kunkel LA, Fisher RI. Phase II study of rituximab in combination with CHOP chemotherapy in patients with previously untreated, aggressive non-Hodgkin's lymphoma. J Clin Oncol. 2001 Jan 15;19(2):389-97. [https://ascopubs.org/doi/full/10.1200/JCO.2001.19.2.389 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11208830 PubMed]
-# '''LNH 98-5:''' Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jan 24;346(4):235-42. [https://www.nejm.org/doi/full/10.1056/NEJMoa011795 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11807147 PubMed]
+#Vose JM, Link BK, Grossbard ML, Czuczman M, Grillo-Lopez A, Gilman P, Lowe A, Kunkel LA, Fisher RI. Phase II study of rituximab in combination with CHOP chemotherapy in patients with previously untreated, aggressive non-Hodgkin's lymphoma. J Clin Oncol. 2001 Jan 15;19(2):389-97. [https://ascopubs.org/doi/full/10.1200/JCO.2001.19.2.389 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11208830 PubMed]
-## '''Update:''' Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Fermé C, Christian B, Lepage E, Tilly H, Morschhauser F, Gaulard P, Salles G, Bosly A, Gisselbrecht C, Reyes F, Coiffier B. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2005 Jun 20;23(18):4117-26. [http://jco.ascopubs.org/content/23/18/4117.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15867204 PubMed]
+#'''LNH 98-5:''' Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jan 24;346(4):235-42. [https://www.nejm.org/doi/full/10.1056/NEJMoa011795 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11807147 PubMed]
-## '''Update:''' Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S, Lefort S, Marit G, Macro M, Sebban C, Belhadj K, Bordessoule D, Fermé C, Tilly H. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte. Blood. 2010 Sep 23;116(12):2040-5. [http://www.bloodjournal.org/content/116/12/2040.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2951853/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20548096 PubMed] content property of [http://hemonc.org HemOnc.org]
+##'''Update:''' Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Fermé C, Christian B, Lepage E, Tilly H, Morschhauser F, Gaulard P, Salles G, Bosly A, Gisselbrecht C, Reyes F, Coiffier B. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2005 Jun 20;23(18):4117-26. [http://jco.ascopubs.org/content/23/18/4117.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15867204 PubMed]
-## '''Update:''' Mounier N, Heutte N, Thieblemont C, Briere J, Gaulard P, Feugier P, Ghesquieres H, Van Den Neste E, Robu D, Tilly H, Bouabdallah R, Safar V, Coiffier B; Groupe d'Etude des Lymphomes de l'Adulte (GELA). Ten-year relative survival and causes of death in elderly patients treated with R-CHOP or CHOP in the GELA LNH-985 trial. Clin Lymphoma Myeloma Leuk. 2012 Jun;12(3):151-4. Epub 2012 Feb 1. [http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(11)00607-0/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22301063 PubMed]
+##'''Update:''' Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S, Lefort S, Marit G, Macro M, Sebban C, Belhadj K, Bordessoule D, Fermé C, Tilly H. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte. Blood. 2010 Sep 23;116(12):2040-5. [http://www.bloodjournal.org/content/116/12/2040.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2951853/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20548096 PubMed] content property of [http://hemonc.org HemOnc.org]
-# '''NCIC CTG LY.9:''' Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2806%2970664-7/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16648042 PubMed]
+##'''Update:''' Mounier N, Heutte N, Thieblemont C, Briere J, Gaulard P, Feugier P, Ghesquieres H, Van Den Neste E, Robu D, Tilly H, Bouabdallah R, Safar V, Coiffier B; Groupe d'Etude des Lymphomes de l'Adulte (GELA). Ten-year relative survival and causes of death in elderly patients treated with R-CHOP or CHOP in the GELA LNH-985 trial. Clin Lymphoma Myeloma Leuk. 2012 Jun;12(3):151-4. Epub 2012 Feb 1. [http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(11)00607-0/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22301063 PubMed]
-## '''Update:''' Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N; MabThera International Trial (MInT) Group. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011 Oct;12(11):1013-22. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2811%2970235-2/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21940214 PubMed]
+#'''NCIC CTG LY.9:''' Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2806%2970664-7/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16648042 PubMed]
-# '''ECOG E4494/CALGB 9793:''' Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, Dakhil SR, Woda B, Fisher RI, Peterson BA, Horning SJ. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006 Jul 1;24(19):3121-7. Epub 2006 Jun 5. [http://jco.ascopubs.org/content/24/19/3121.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16754935 PubMed]
+##'''Update:''' Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N; MabThera International Trial (MInT) Group. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011 Oct;12(11):1013-22. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2811%2970235-2/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21940214 PubMed]
-# '''SWOG S0014:''' Persky DO, Unger JM, Spier CM, Stea B, LeBlanc M, McCarty MJ, Rimsza LM, Fisher RI, Miller TP; Southwest Oncology Group. Phase II study of rituximab plus three cycles of CHOP and involved-field radiotherapy for patients with limited-stage aggressive B-cell lymphoma: Southwest Oncology Group study 0014. J Clin Oncol. 2008 May 10;26(14):2258-63. Epub 2008 Apr 14. [http://jco.ascopubs.org/content/26/14/2258.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18413640 PubMed]
+#'''ECOG E4494/CALGB 9793:''' Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, Dakhil SR, Woda B, Fisher RI, Peterson BA, Horning SJ. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006 Jul 1;24(19):3121-7. Epub 2006 Jun 5. [http://jco.ascopubs.org/content/24/19/3121.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16754935 PubMed]
-# '''IELSG-10:''' Vitolo U, Chiappella A, Ferreri AJ, Martelli M, Baldi I, Balzarotti M, Bottelli C, Conconi A, Gomez H, Lopez-Guillermo A, Martinelli G, Merli F, Novero D, Orsucci L, Pavone V, Ricardi U, Storti S, Gospodarowicz MK, Cavalli F, Sarris AH, Zucca E. First-line treatment for primary testicular diffuse large B-cell lymphoma with rituximab-CHOP, CNS prophylaxis, and contralateral testis irradiation: final results of an international phase II trial. J Clin Oncol. 2011 Jul 10;29(20):2766-72. Epub 2011 Jun 6. [http://jco.ascopubs.org/content/29/20/2766.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21646602 PubMed]
+#'''SWOG S0014:''' Persky DO, Unger JM, Spier CM, Stea B, LeBlanc M, McCarty MJ, Rimsza LM, Fisher RI, Miller TP; Southwest Oncology Group. Phase II study of rituximab plus three cycles of CHOP and involved-field radiotherapy for patients with limited-stage aggressive B-cell lymphoma: Southwest Oncology Group study 0014. J Clin Oncol. 2008 May 10;26(14):2258-63. Epub 2008 Apr 14. [http://jco.ascopubs.org/content/26/14/2258.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18413640 PubMed]
-# '''ANZINTER3:''' Merli F, Luminari S, Rossi G, Mammi C, Marcheselli L, Tucci A, Ilariucci F, Chiappella A, Musso M, Di Rocco A, Stelitano C, Alvarez I, Baldini L, Mazza P, Salvi F, Arcari A, Fragasso A, Gobbi PG, Liberati AM, Federico M. Cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab versus epirubicin, cyclophosphamide, vinblastine, prednisone and rituximab for the initial treatment of elderly "fit" patients with diffuse large B-cell lymphoma: results from the ANZINTER3 trial of the Intergruppo Italiano Linfomi. Leuk Lymphoma. 2012 Apr;53(4):581-8. Epub 2011 Nov 15. [https://www.tandfonline.com/doi/full/10.3109/10428194.2011.621565 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21895543 PubMed]
+#'''IELSG-10:''' Vitolo U, Chiappella A, Ferreri AJ, Martelli M, Baldi I, Balzarotti M, Bottelli C, Conconi A, Gomez H, Lopez-Guillermo A, Martinelli G, Merli F, Novero D, Orsucci L, Pavone V, Ricardi U, Storti S, Gospodarowicz MK, Cavalli F, Sarris AH, Zucca E. First-line treatment for primary testicular diffuse large B-cell lymphoma with rituximab-CHOP, CNS prophylaxis, and contralateral testis irradiation: final results of an international phase II trial. J Clin Oncol. 2011 Jul 10;29(20):2766-72. Epub 2011 Jun 6. [http://jco.ascopubs.org/content/29/20/2766.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21646602 PubMed]
-# '''LNH03-2B:''' Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, Thiéblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquières H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011 Nov 26;378(9806):1858-67. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61040-4/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22118442 PubMed]
+#'''ANZINTER3:''' Merli F, Luminari S, Rossi G, Mammi C, Marcheselli L, Tucci A, Ilariucci F, Chiappella A, Musso M, Di Rocco A, Stelitano C, Alvarez I, Baldini L, Mazza P, Salvi F, Arcari A, Fragasso A, Gobbi PG, Liberati AM, Federico M. Cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab versus epirubicin, cyclophosphamide, vinblastine, prednisone and rituximab for the initial treatment of elderly "fit" patients with diffuse large B-cell lymphoma: results from the ANZINTER3 trial of the Intergruppo Italiano Linfomi. Leuk Lymphoma. 2012 Apr;53(4):581-8. Epub 2011 Nov 15. [https://www.tandfonline.com/doi/full/10.3109/10428194.2011.621565 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21895543 PubMed]
-## '''Subgroup analysis:''' Molina TJ, Canioni D, Copie-Bergman C, Recher C, Brière J, Haioun C, Berger F, Fermé C, Copin MC, Casasnovas O, Thieblemont C, Petrella T, Leroy K, Salles G, Fabiani B, Morschauser F, Mounier N, Coiffier B, Jardin F, Gaulard P, Jais JP, Tilly H. Young patients with non-germinal center B-cell-like diffuse large B-cell lymphoma benefit from intensified chemotherapy with ACVBP plus rituximab compared with CHOP plus rituximab: analysis of data from the Groupe d'Etudes des Lymphomes de l'Adulte/lymphoma study association phase III trial LNH 03-2B. J Clin Oncol. 2014 Dec 10;32(35):3996-4003. Epub 2014 Nov 10. [https://ascopubs.org/doi/full/10.1200/JCO.2013.54.9493 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25385729 PubMed]
+#'''LNH03-2B:''' Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, Thiéblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquières H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011 Nov 26;378(9806):1858-67. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61040-4/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22118442 PubMed]
-# '''LNH03-6B:''' Delarue R, Tilly H, Mounier N, Petrella T, Salles G, Thieblemont C, Bologna S, Ghesquières H, Hacini M, Fruchart C, Ysebaert L, Fermé C, Casasnovas O, Van Hoof A, Thyss A, Delmer A, Fitoussi O, Molina TJ, Haioun C, Bosly A. Dose-dense rituximab-CHOP compared with standard rituximab-CHOP in elderly patients with diffuse large B-cell lymphoma (the LNH03-6B study): a randomised phase 3 trial. Lancet Oncol. 2013 May;14(6):525-33. Epub 2013 Apr 9. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70122-0/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23578722 PubMed]
+##'''Subgroup analysis:''' Molina TJ, Canioni D, Copie-Bergman C, Recher C, Brière J, Haioun C, Berger F, Fermé C, Copin MC, Casasnovas O, Thieblemont C, Petrella T, Leroy K, Salles G, Fabiani B, Morschauser F, Mounier N, Coiffier B, Jardin F, Gaulard P, Jais JP, Tilly H. Young patients with non-germinal center B-cell-like diffuse large B-cell lymphoma benefit from intensified chemotherapy with ACVBP plus rituximab compared with CHOP plus rituximab: analysis of data from the Groupe d'Etudes des Lymphomes de l'Adulte/lymphoma study association phase III trial LNH 03-2B. J Clin Oncol. 2014 Dec 10;32(35):3996-4003. Epub 2014 Nov 10. [https://ascopubs.org/doi/full/10.1200/JCO.2013.54.9493 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25385729 PubMed]
-# '''PIX203:''' Herbrecht R, Cernohous P, Engert A, Le Gouill S, Macdonald D, Machida C, Myint H, Saleh A, Singer J, Wilhelm M, van der Jagt R. Comparison of pixantrone-based regimen (CPOP-R) with doxorubicin-based therapy (CHOP-R) for treatment of diffuse large B-cell lymphoma. Ann Oncol. 2013 Oct;24(10):2618-23. Epub 2013 Aug 14. [https://academic.oup.com/annonc/article/24/10/2618/177246 link to original article] '''contains verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/23946328 PubMed]
+#'''LNH03-6B:''' Delarue R, Tilly H, Mounier N, Petrella T, Salles G, Thieblemont C, Bologna S, Ghesquières H, Hacini M, Fruchart C, Ysebaert L, Fermé C, Casasnovas O, Van Hoof A, Thyss A, Delmer A, Fitoussi O, Molina TJ, Haioun C, Bosly A. Dose-dense rituximab-CHOP compared with standard rituximab-CHOP in elderly patients with diffuse large B-cell lymphoma (the LNH03-6B study): a randomised phase 3 trial. Lancet Oncol. 2013 May;14(6):525-33. Epub 2013 Apr 9. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70122-0/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23578722 PubMed]
-# '''MDACC 2005-0054:''' Oki Y, Westin JR, Vega F, Chuang H, Fowler N, Neelapu S, Hagemeister FB, McLaughlin P, Kwak LW, Romaguera JE, Fanale M, Younes A, Rodriguez MA, Orlowski RZ, Wang M, Ouzounian ST, Samaniego F, Fayad L. Prospective phase II study of rituximab with alternating cycles of hyper-CVAD and high-dose methotrexate with cytarabine for young patients with high-risk diffuse large B-cell lymphoma. Br J Haematol. 2013 Dec;163(5):611-20. Epub 2013 Oct 1. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.12585/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278952/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24117234 PubMed]
+#'''PIX203:''' Herbrecht R, Cernohous P, Engert A, Le Gouill S, Macdonald D, Machida C, Myint H, Saleh A, Singer J, Wilhelm M, van der Jagt R. Comparison of pixantrone-based regimen (CPOP-R) with doxorubicin-based therapy (CHOP-R) for treatment of diffuse large B-cell lymphoma. Ann Oncol. 2013 Oct;24(10):2618-23. Epub 2013 Aug 14. [https://academic.oup.com/annonc/article/24/10/2618/177246 link to original article] '''contains verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/23946328 PubMed]
-# '''SWOG S9704:''' Stiff PJ, Unger JM, Cook JR, Constine LS, Couban S, Stewart DA, Shea TC, Porcu P, Winter JN, Kahl BS, Miller TP, Tubbs RR, Marcellus D, Friedberg JW, Barton KP, Mills GM, LeBlanc M, Rimsza LM, Forman SJ, Fisher RI. Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. N Engl J Med. 2013 Oct 31;369(18):1681-90. [https://www.nejm.org/doi/full/10.1056/NEJMoa1301077 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985418/ link to PMC article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24171516 PubMed]
+#'''MDACC 2005-0054:''' Oki Y, Westin JR, Vega F, Chuang H, Fowler N, Neelapu S, Hagemeister FB, McLaughlin P, Kwak LW, Romaguera JE, Fanale M, Younes A, Rodriguez MA, Orlowski RZ, Wang M, Ouzounian ST, Samaniego F, Fayad L. Prospective phase II study of rituximab with alternating cycles of hyper-CVAD and high-dose methotrexate with cytarabine for young patients with high-risk diffuse large B-cell lymphoma. Br J Haematol. 2013 Dec;163(5):611-20. Epub 2013 Oct 1. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.12585/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278952/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24117234 PubMed]
-## '''Subgroup analysis:''' Puvvada SD, Stiff PJ, Leblanc M, Cook JR, Couban S, Leonard JP, Kahl B, Marcellus D, Shea TC, Winter JN, Li H, Rimsza LM, Friedberg JW, Smith SM. Outcomes of MYC-associated lymphomas after R-CHOP with and without consolidative autologous stem cell transplant: subset analysis of randomized trial intergroup SWOG S9704. Br J Haematol. 2016 Sep;174(5):686-91. Epub 2016 Apr 13. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.14100/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125530/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27072903 PubMed]
+#'''SWOG S9704:''' Stiff PJ, Unger JM, Cook JR, Constine LS, Couban S, Stewart DA, Shea TC, Porcu P, Winter JN, Kahl BS, Miller TP, Tubbs RR, Marcellus D, Friedberg JW, Barton KP, Mills GM, LeBlanc M, Rimsza LM, Forman SJ, Fisher RI. Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. N Engl J Med. 2013 Oct 31;369(18):1681-90. [https://www.nejm.org/doi/full/10.1056/NEJMoa1301077 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985418/ link to PMC article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24171516 PubMed]
-# '''MAIN:''' Seymour JF, Pfreundschuh M, Trnený M, Sehn LH, Catalano J, Csinady E, Moore N, Coiffier B; MAIN Study Investigators. R-CHOP with or without bevacizumab in patients with previously untreated diffuse large B-cell lymphoma: final MAIN study outcomes. Haematologica. 2014 Aug;99(8):1343-9. Epub 2014 Jun 3. [http://www.haematologica.org/content/99/8/1343.abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116833/ link to PMC article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24895339 PubMed]
+##'''Subgroup analysis:''' Puvvada SD, Stiff PJ, Leblanc M, Cook JR, Couban S, Leonard JP, Kahl B, Marcellus D, Shea TC, Winter JN, Li H, Rimsza LM, Friedberg JW, Smith SM. Outcomes of MYC-associated lymphomas after R-CHOP with and without consolidative autologous stem cell transplant: subset analysis of randomized trial intergroup SWOG S9704. Br J Haematol. 2016 Sep;174(5):686-91. Epub 2016 Apr 13. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.14100/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125530/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27072903 PubMed]
+#'''MAIN:''' Seymour JF, Pfreundschuh M, Trnený M, Sehn LH, Catalano J, Csinady E, Moore N, Coiffier B; MAIN Study Investigators. R-CHOP with or without bevacizumab in patients with previously untreated diffuse large B-cell lymphoma: final MAIN study outcomes. Haematologica. 2014 Aug;99(8):1343-9. Epub 2014 Jun 3. [http://www.haematologica.org/content/99/8/1343.abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116833/ link to PMC article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24895339 PubMed]
 <!-- Prior publication: Poster presentation at the 2014 annual meeting of the American Society of Hematology (Howlett C, Landsburg DJ, Chong EA, Snedecor SJ, Schuster SJ, Green TM, Cohen JB, Svoboda J, Nasta SD, Feldman T, Rago R, Land D, Walsh KM, Goy A, Mato AR. Front-line, dose-escalated immunochemotherapy is associated with a significant PFS (but not OS) advantage in 401 patients (pts) with double-hit lymphomas (DHL): A systematic review and meta-analysis. Blood, 124, abst 3056). -->
-# '''Retrospective:''' Howlett C, Snedecor SJ, Landsburg DJ, Svoboda J, Chong EA, Schuster SJ, Nasta SD, Feldman T, Rago A, Walsh KM, Weber S, Goy A, Mato A. Front-line, dose-escalated immunochemotherapy is associated with a significant progression-free survival advantage in patients with double-hit lymphomas: a systematic review and meta-analysis. Br J Haematol. 2015 Aug;170(4):504-14. Epub 2015 Apr 24. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13463/full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25907897 PubMed]
+#'''Retrospective:''' Howlett C, Snedecor SJ, Landsburg DJ, Svoboda J, Chong EA, Schuster SJ, Nasta SD, Feldman T, Rago A, Walsh KM, Weber S, Goy A, Mato A. Front-line, dose-escalated immunochemotherapy is associated with a significant progression-free survival advantage in patients with double-hit lymphomas: a systematic review and meta-analysis. Br J Haematol. 2015 Aug;170(4):504-14. Epub 2015 Apr 24. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13463/full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25907897 PubMed]
-# '''ECOG E3402:''' Witzig TE, Hong F, Micallef IN, Gascoyne RD, Dogan A, Wagner H Jr, Kahl BS, Advani RH, Horning SJ. A phase II trial of RCHOP followed by radioimmunotherapy for early stage (stages I/II) diffuse large B-cell non-Hodgkin lymphoma: ECOG3402. Br J Haematol. 2015 Sep;170(5):679-86. Epub 2015 May 14. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13493/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691189/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25974212 PubMed]
+#'''ECOG E3402:''' Witzig TE, Hong F, Micallef IN, Gascoyne RD, Dogan A, Wagner H Jr, Kahl BS, Advani RH, Horning SJ. A phase II trial of RCHOP followed by radioimmunotherapy for early stage (stages I/II) diffuse large B-cell non-Hodgkin lymphoma: ECOG3402. Br J Haematol. 2015 Sep;170(5):679-86. Epub 2015 May 14. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13493/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691189/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25974212 PubMed]
-# '''LYM-2034:''' Offner F, Samoilova O, Osmanov E, Eom HS, Topp MS, Raposo J, Pavlov V, Ricci D, Chaturvedi S, Zhu E, van de Velde H, Enny C, Rizo A, Ferhanoglu B. Frontline rituximab, cyclophosphamide, doxorubicin, and prednisone with bortezomib (VR-CAP) or vincristine (R-CHOP) for non-GCB DLBCL. Blood. 2015 Oct 15;126(16):1893-901. Epub 2015 Jul 31. [http://www.bloodjournal.org/content/126/16/1893.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616024/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26232170 PubMed]
+#'''LYM-2034:''' Offner F, Samoilova O, Osmanov E, Eom HS, Topp MS, Raposo J, Pavlov V, Ricci D, Chaturvedi S, Zhu E, van de Velde H, Enny C, Rizo A, Ferhanoglu B. Frontline rituximab, cyclophosphamide, doxorubicin, and prednisone with bortezomib (VR-CAP) or vincristine (R-CHOP) for non-GCB DLBCL. Blood. 2015 Oct 15;126(16):1893-901. Epub 2015 Jul 31. [http://www.bloodjournal.org/content/126/16/1893.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616024/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26232170 PubMed]
-# '''CISL 12-09:''' Yoon DH, Sohn BS, Oh SY, Lee WS, Lee SM, Yang DH, Huh J, Suh C. Feasibility of abbreviated cycles of immunochemotherapy for completely resected limited-stage CD20+ diffuse large B-cell lymphoma (CISL 12-09). Oncotarget. 2017 Feb 21;8(8):13367-13374. [http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=14531&path%5B%5D=46365 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355104/ link to PMC article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28076329 PubMed]
+#'''CISL 12-09:''' Yoon DH, Sohn BS, Oh SY, Lee WS, Lee SM, Yang DH, Huh J, Suh C. Feasibility of abbreviated cycles of immunochemotherapy for completely resected limited-stage CD20+ diffuse large B-cell lymphoma (CISL 12-09). Oncotarget. 2017 Feb 21;8(8):13367-13374. [http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=14531&path%5B%5D=46365 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355104/ link to PMC article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28076329 PubMed]
-# '''MabEase:''' Lugtenburg P, Avivi I, Berenschot H, Ilhan O, Marolleau JP, Nagler A, Rueda A, Tani M, Turgut M, Osborne S, Smith R, Pfreundschuh M. Efficacy and safety of subcutaneous and intravenous rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in first-line diffuse large B-cell lymphoma: the randomized MabEase study. Haematologica. 2017 Nov;102(11):1913-1922. Epub 2017 Sep 21. [http://www.haematologica.org/content/102/11/1913 link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28935843 PubMed]
+#'''MabEase:''' Lugtenburg P, Avivi I, Berenschot H, Ilhan O, Marolleau JP, Nagler A, Rueda A, Tani M, Turgut M, Osborne S, Smith R, Pfreundschuh M. Efficacy and safety of subcutaneous and intravenous rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in first-line diffuse large B-cell lymphoma: the randomized MabEase study. Haematologica. 2017 Nov;102(11):1913-1922. Epub 2017 Sep 21. [http://www.haematologica.org/content/102/11/1913 link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28935843 PubMed]
-# '''GOYA:''' Vitolo U, Trněný M, Belada D, Burke JM, Carella AM, Chua N, Abrisqueta P, Demeter J, Flinn I, Hong X, Kim WS, Pinto A, Shi YK, Tatsumi Y, Oestergaard MZ, Wenger M, Fingerle-Rowson G, Catalani O, Nielsen T, Martelli M, Sehn LH. Obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in previously untreated diffuse large B-cell lymphoma. J Clin Oncol. 2017 Nov 1;35(31):3529-3537. Epub 2017 Aug 10. [https://ascopubs.org/doi/full/10.1200/JCO.2017.73.3402 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28796588 PubMed]
+#'''GOYA:''' Vitolo U, Trněný M, Belada D, Burke JM, Carella AM, Chua N, Abrisqueta P, Demeter J, Flinn I, Hong X, Kim WS, Pinto A, Shi YK, Tatsumi Y, Oestergaard MZ, Wenger M, Fingerle-Rowson G, Catalani O, Nielsen T, Martelli M, Sehn LH. Obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in previously untreated diffuse large B-cell lymphoma. J Clin Oncol. 2017 Nov 1;35(31):3529-3537. Epub 2017 Aug 10. [https://ascopubs.org/doi/full/10.1200/JCO.2017.73.3402 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28796588 PubMed]
-# '''C05013:''' Leonard JP, Kolibaba KS, Reeves JA, Tulpule A, Flinn IW, Kolevska T, Robles R, Flowers CR, Collins R, DiBella NJ, Papish SW, Venugopal P, Horodner A, Tabatabai A, Hajdenberg J, Park J, Neuwirth R, Mulligan G, Suryanarayan K, Esseltine DL, de Vos S. Randomized phase II study of R-CHOP with or without bortezomib in previously untreated patients with non-germinal center B-cell-like diffuse large B-cell lymphoma. J Clin Oncol. 2017 Nov 1;35(31):3538-3546. Epub 2017 Sep 1. [https://ascopubs.org/doi/full/10.1200/JCO.2017.73.2784 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28862883 PubMed]
+#'''C05013:''' Leonard JP, Kolibaba KS, Reeves JA, Tulpule A, Flinn IW, Kolevska T, Robles R, Flowers CR, Collins R, DiBella NJ, Papish SW, Venugopal P, Horodner A, Tabatabai A, Hajdenberg J, Park J, Neuwirth R, Mulligan G, Suryanarayan K, Esseltine DL, de Vos S. Randomized phase II study of R-CHOP with or without bortezomib in previously untreated patients with non-germinal center B-cell-like diffuse large B-cell lymphoma. J Clin Oncol. 2017 Nov 1;35(31):3538-3546. Epub 2017 Sep 1. [https://ascopubs.org/doi/full/10.1200/JCO.2017.73.2784 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28862883 PubMed]
-# Hara T, Yoshikawa T, Goto H, Sawada M, Yamada T, Fukuno K, Kasahara S, Shibata Y, Matsumoto T, Mabuchi R, Nakamura N, Nakamura H, Ninomiya S, Kitagawa J, Kanemura N, Nannya Y, Katsumura N, Takahashi T, Kito Y, Takami T, Miyazaki T, Takeuchi T, Shimizu M, Tsurumi H. R-THP-COP versus R-CHOP in patients younger than 70 years with untreated diffuse large B cell lymphoma: A randomized, open-label, noninferiority phase 3 trial. Hematol Oncol. 2018 Oct;36(4):638-644. Epub 2018 Jun 8. [https://onlinelibrary.wiley.com/doi/abs/10.1002/hon.2524 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29882279 PubMed]
+#Hara T, Yoshikawa T, Goto H, Sawada M, Yamada T, Fukuno K, Kasahara S, Shibata Y, Matsumoto T, Mabuchi R, Nakamura N, Nakamura H, Ninomiya S, Kitagawa J, Kanemura N, Nannya Y, Katsumura N, Takahashi T, Kito Y, Takami T, Miyazaki T, Takeuchi T, Shimizu M, Tsurumi H. R-THP-COP versus R-CHOP in patients younger than 70 years with untreated diffuse large B cell lymphoma: A randomized, open-label, noninferiority phase 3 trial. Hematol Oncol. 2018 Oct;36(4):638-644. Epub 2018 Jun 8. [https://onlinelibrary.wiley.com/doi/abs/10.1002/hon.2524 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29882279 PubMed]
-# '''CSWOG0001:''' Li X, Huang H, Xu B, Guo H, Lin Y, Ye S, Yi J, Li W, Wu X, Wang W, Zhan H, Xie D, Peng J, Cao Y, Pu X, Guo C, Hong H, Wang Z, Fang X, Zhou Y, Lin S, Liu Q, Lin T. Dose-Dense Rituximab-CHOP versus Standard Rituximab-CHOP in Newly Diagnosed Chinese Patients with Diffuse Large B-Cell Lymphoma: A Randomized, Multicenter, Open-Label Phase 3 Trial. Cancer Res Treat. 2019 Jul;51(3):919-932. Epub 2018 Oct 2. [https://www.e-crt.org/journal/view.php?doi=10.4143/crt.2018.230 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639223/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30282447 PubMed]
+#'''CSWOG0001:''' Li X, Huang H, Xu B, Guo H, Lin Y, Ye S, Yi J, Li W, Wu X, Wang W, Zhan H, Xie D, Peng J, Cao Y, Pu X, Guo C, Hong H, Wang Z, Fang X, Zhou Y, Lin S, Liu Q, Lin T. Dose-Dense Rituximab-CHOP versus Standard Rituximab-CHOP in Newly Diagnosed Chinese Patients with Diffuse Large B-Cell Lymphoma: A Randomized, Multicenter, Open-Label Phase 3 Trial. Cancer Res Treat. 2019 Jul;51(3):919-932. Epub 2018 Oct 2. [https://www.e-crt.org/journal/view.php?doi=10.4143/crt.2018.230 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639223/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30282447 PubMed]
-# '''PHOENIX:''' Younes A, Sehn LH, Johnson P, Zinzani PL, Hong X, Zhu J, Patti C, Belada D, Samoilova O, Suh C, Leppä S, Rai S, Turgut M, Jurczak W, Cheung MC, Gurion R, Yeh SP, Lopez-Hernandez A, Dührsen U, Thieblemont C, Chiattone CS, Balasubramanian S, Carey J, Liu G, Shreeve SM, Sun S, Zhuang SH, Vermeulen J, Staudt LM, Wilson W; PHOENIX investigators. Randomized phase III trial of ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in non-germinal center B-cell diffuse large B-cell lymphoma. J Clin Oncol. 2019 May 20;37(15):1285-1295. Epub 2019 Mar 22. [https://ascopubs.org/doi/full/10.1200/JCO.18.02403 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6553835/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/30901302 PubMed]
+#'''PHOENIX:''' Younes A, Sehn LH, Johnson P, Zinzani PL, Hong X, Zhu J, Patti C, Belada D, Samoilova O, Suh C, Leppä S, Rai S, Turgut M, Jurczak W, Cheung MC, Gurion R, Yeh SP, Lopez-Hernandez A, Dührsen U, Thieblemont C, Chiattone CS, Balasubramanian S, Carey J, Liu G, Shreeve SM, Sun S, Zhuang SH, Vermeulen J, Staudt LM, Wilson W; PHOENIX investigators. Randomized phase III trial of ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in non-germinal center B-cell diffuse large B-cell lymphoma. J Clin Oncol. 2019 May 20;37(15):1285-1295. Epub 2019 Mar 22. [https://ascopubs.org/doi/full/10.1200/JCO.18.02403 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6553835/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/30901302 PubMed]
 <!-- # '''Abstract:''' Wyndham H. Wilson, MD, PhD, Jung sin-Ho, Brandelyn Nicole Pitcher, MS, Eric D Hsi, MD, Jonathan Friedberg, MD, Bruce Cheson, MD, Nancy L Bartlett, MD, Scott Smith, Nina Wagner Johnston, MD, Brad S Kahl, Louis M. Staudt, MD, PhD, Kristie Blum, MD, Jeremy Abramson, Oliver W Press, MD, PhD, Richard I. Fisher, MD, Kristy L. Richards, PhD, MD, Heiko Schoder, MD, Julie E Chang, Andrew D. Zelenetz and John P. Leonard, MD. Phase III Randomized Study of R-CHOP Versus DA-EPOCH-R and Molecular Analysis of Untreated Diffuse Large B-Cell Lymphoma: CALGB/Alliance 50303. ASH 2016 Abstract 469 [https://ashpublications.org/blood/article/128/22/469/101297/Phase-III-Randomized-Study-of-R-CHOP-Versus-DA link to abstract] -->
-# '''CALGB 50303:''' Bartlett NL, Wilson WH, Jung SH, Hsi ED, Maurer MJ, Pederson LD, Polley MC, Pitcher BN, Cheson BD, Kahl BS, Friedberg JW, Staudt LM, Wagner-Johnston ND, Blum KA, Abramson JS, Reddy NM, Winter JN, Chang JE, Gopal AK, Chadburn A, Mathew S, Fisher RI, Richards KL, Schöder H, Zelenetz AD, Leonard JP. Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303. J Clin Oncol. 2019 Jul 20;37(21):1790-1799. Epub 2019 Apr 2. [https://ascopubs.org/doi/full/10.1200/JCO.18.01994 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774813/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/30939090 PubMed]
+#'''CALGB 50303:''' Bartlett NL, Wilson WH, Jung SH, Hsi ED, Maurer MJ, Pederson LD, Polley MC, Pitcher BN, Cheson BD, Kahl BS, Friedberg JW, Staudt LM, Wagner-Johnston ND, Blum KA, Abramson JS, Reddy NM, Winter JN, Chang JE, Gopal AK, Chadburn A, Mathew S, Fisher RI, Richards KL, Schöder H, Zelenetz AD, Leonard JP. Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303. J Clin Oncol. 2019 Jul 20;37(21):1790-1799. Epub 2019 Apr 2. [https://ascopubs.org/doi/full/10.1200/JCO.18.01994 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774813/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/30939090 PubMed]
-# '''FLYER:''' Poeschel V, Held G, Ziepert M, Witzens-Harig M, Holte H, Thurner L, Borchmann P, Viardot A, Soekler M, Keller U, Schmidt C, Truemper L, Mahlberg R, Marks R, Hoeffkes HG, Metzner B, Dierlamm J, Frickhofen N, Haenel M, Neubauer A, Kneba M, Merli F, Tucci A, de Nully Brown P, Federico M, Lengfelder E, di Rocco A, Trappe R, Rosenwald A, Berdel C, Maisenhoelder M, Shpilberg O, Amam J, Christofyllakis K, Hartmann F, Murawski N, Stilgenbauer S, Nickelsen M, Wulf G, Glass B, Schmitz N, Altmann B, Loeffler M, Pfreundschuh M; FLYER Trial Investigators; German Lymphoma Alliance. Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER): a randomised, phase 3, non-inferiority trial. Lancet. 2019 Dec 21;394(10216):2271-2281. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)33008-9/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/31868632 PubMed]
+#'''FLYER:''' Poeschel V, Held G, Ziepert M, Witzens-Harig M, Holte H, Thurner L, Borchmann P, Viardot A, Soekler M, Keller U, Schmidt C, Truemper L, Mahlberg R, Marks R, Hoeffkes HG, Metzner B, Dierlamm J, Frickhofen N, Haenel M, Neubauer A, Kneba M, Merli F, Tucci A, de Nully Brown P, Federico M, Lengfelder E, di Rocco A, Trappe R, Rosenwald A, Berdel C, Maisenhoelder M, Shpilberg O, Amam J, Christofyllakis K, Hartmann F, Murawski N, Stilgenbauer S, Nickelsen M, Wulf G, Glass B, Schmitz N, Altmann B, Loeffler M, Pfreundschuh M; FLYER Trial Investigators; German Lymphoma Alliance. Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER): a randomised, phase 3, non-inferiority trial. Lancet. 2019 Dec 21;394(10216):2271-2281. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)33008-9/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/31868632 PubMed]
 ==R-CHOP (Prednisolone) {{#subobject:875cc2|Regimen=1}}==
@@ Line 707: / Line 759: @@
 R-CHOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisolone
 ===Example orders===
 *[[Example orders for R-CHOP in lymphoma]]
 ===Regimen variant #1, prednisolone 40 mg/m<sup>2</sup> {{#subobject:74f424|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-!style="width: 20%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
 |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)60313-X/fulltext Cunningham et al. 2013 (UK NCRI R-CHOP14v21)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#R-CHOP-14_.28Prednisolone.29|R-CHOP-14]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |
 |-
 |[https://www.ejcancer.com/article/S0959-8049(16)00088-5/fulltext Fridrik et al. 2016 (AGMT NHL-14)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |R-COMP
-|style="background-color:#ffffbf"|Did not meet secondary efficacy endpoints
+| style="background-color:#ffffbf" |Did not meet secondary efficacy endpoints
-|style="background-color:#ffffbf"|Did not meet primary endpoint of reduced cardiotoxicity
+| style="background-color:#ffffbf" |Did not meet primary endpoint of reduced cardiotoxicity
 |-
 |}
 ''Note: Cunningham et al. 2013 states that the regimen is based on LNH 98-5, but notably it uses prednisolone instead of prednisone. AGMT NHL-14 states that R-CHOP was "given in standard doses" per LNH 98-5, but this regimen uses prednisone, whereas the title and text of Fridrik et al. 2016 implies that prednisolone was used. The authors have confirmed that prednisolone was used, due to prednisone not being available in Austria.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 739: / Line 794: @@
 ====CNS prophylaxis====
 Per investigator discretion, but Cunningham et al. 2013 recommended that patients who had involvement of the "bone marrow, peripheral blood, nasal or paranasal sinuses, orbit, and testis" (they probably intended to say "or testis") receive:
 *[[Methotrexate (MTX)]] 12.5 mg IT "for the first three cycles of treatment, administered as per local guidelines." No other details given.
 ====Supportive medications====
 *Described in Cunningham et al. 2013
 *[[Lenograstim (Granocyte)]] (dose/route not specified) given on days 4 to 12 at physician discretion
@@ Line 751: / Line 808: @@
 ===Regimen variant #2, prednisolone 100 mg, capped vincristine, 4 cycles {{#subobject:1cbzib|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-!style="width: 20%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
 |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)33008-9/fulltext Poeschel et al. 2019 (FLYER)]
-|style="background-color:#1a9851"|Phase III (E-de-esc)
+| style="background-color:#1a9851" |Phase III (E-de-esc)
 |[[#R-CHOP|R-CHOP]] x 6
-|style="background-color:#eeee01"|Non-inferior PFS36
+| style="background-color:#eeee01" |Non-inferior PFS36
 | style="background-color:#1a9850" |Less toxic
 |-
@@ Line 766: / Line 823: @@
 ''Note: Patients in FLYER were 18 to 60 and had no risk factors according to age-adjusted IPI.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] as follows:
@@ Line 780: / Line 838: @@
 ===Regimen variant #3, prednisolone 100 mg, 6 cycles {{#subobject:74f454|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-!style="width: 20%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494978/ Davies et al. 2019 (REMoDL-B)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[Diffuse_large_B-cell_lymphoma_-_historical#VR-CHOP|RB-CHOP]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS30
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS30
 |
 |-
 |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)33008-9/fulltext Poeschel et al. 2019 (FLYER)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#R-CHOP|R-CHOP]] x 4
-|style="background-color:#eeee01"|Non-inferior PFS36
+| style="background-color:#eeee01" |Non-inferior PFS36
 | style="background-color:#d73027" |More toxic
 |-
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 810: / Line 869: @@
 ===Regimen variant #4, prednisolone 100 mg/m<sup>2</sup> {{#subobject:74f454|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://journal.waocp.org/?sid=Entrez:PubMed&id=pmid:27039799&key=2016.17.3.1513 Payandeh et al. 2016]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#R-CHOP-14_.28Prednisolone.29|R-CHOP-14]]
 | style="background-color:#d73027" |Inferior OS
@@ Line 822: / Line 881: @@
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 831: / Line 891: @@
 ===References===
-# '''UK NCRI R-CHOP14v21:''' Cunningham D, Hawkes EA, Jack A, Qian W, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford JA, McMillan A, Davies J, Turner D, Kruger A, Johnson P, Gambell J, Linch D. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet. 2013 May 25;381(9880):1817-26. Epub 2013 Apr 22. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)60313-X/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23615461 PubMed]
-# '''AGMT NHL-14:''' Fridrik MA, Jaeger U, Petzer A, Willenbacher W, Keil F, Lang A, Andel J, Burgstaller S, Krieger O, Oberaigner W, Sihorsch K, Greil R. Cardiotoxicity with rituximab, cyclophosphamide, non-pegylated liposomal doxorubicin, vincristine and prednisolone compared to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone in frontline treatment of patients with diffuse large B-cell lymphoma: A randomised phase-III study from the Austrian Cancer Drug Therapy Working Group [Arbeitsgemeinschaft Medikamentöse Tumortherapie AGMT](NHL-14). Eur J Cancer. 2016 May;58:112-21. Epub 2016 Mar 15. [https://www.ejcancer.com/article/S0959-8049(16)00088-5/fulltext link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26990931 PubMed]
+#'''UK NCRI R-CHOP14v21:''' Cunningham D, Hawkes EA, Jack A, Qian W, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford JA, McMillan A, Davies J, Turner D, Kruger A, Johnson P, Gambell J, Linch D. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet. 2013 May 25;381(9880):1817-26. Epub 2013 Apr 22. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)60313-X/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23615461 PubMed]
-# Payandeh M, Najafi S, Shojaiyan FZ, Sadeghi M. Phase III of study of R-CHOP-21 vs R-CHOP-14 for untreated stage III and IV B-cell non-Hodgkin's lymphoma: a report from Iran. Asian Pac J Cancer Prev. 2016;17(3):1513-7. [http://journal.waocp.org/?sid=Entrez:PubMed&id=pmid:27039799&key=2016.17.3.1513 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27039799 PubMed]
+#'''AGMT NHL-14:''' Fridrik MA, Jaeger U, Petzer A, Willenbacher W, Keil F, Lang A, Andel J, Burgstaller S, Krieger O, Oberaigner W, Sihorsch K, Greil R. Cardiotoxicity with rituximab, cyclophosphamide, non-pegylated liposomal doxorubicin, vincristine and prednisolone compared to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone in frontline treatment of patients with diffuse large B-cell lymphoma: A randomised phase-III study from the Austrian Cancer Drug Therapy Working Group [Arbeitsgemeinschaft Medikamentöse Tumortherapie AGMT](NHL-14). Eur J Cancer. 2016 May;58:112-21. Epub 2016 Mar 15. [https://www.ejcancer.com/article/S0959-8049(16)00088-5/fulltext link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26990931 PubMed]
-# '''REMoDL-B:''' Davies A, Cummin TE, Barrans S, Maishman T, Mamot C, Novak U, Caddy J, Stanton L, Kazmi-Stokes S, McMillan A, Fields P, Pocock C, Collins GP, Stephens R, Cucco F, Clipson A, Sha C, Tooze R, Care MA, Griffiths G, Du MQ, Westhead DR, Burton C, Johnson PWM. Gene-expression profiling of bortezomib added to standard chemoimmunotherapy for diffuse large B-cell lymphoma (REMoDL-B): an open-label, randomised, phase 3 trial. Lancet Oncol. 2019 May;20(5):649-662. Epub 2019 Apr 1. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30935-5/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494978/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/30948276 PubMed]
+#Payandeh M, Najafi S, Shojaiyan FZ, Sadeghi M. Phase III of study of R-CHOP-21 vs R-CHOP-14 for untreated stage III and IV B-cell non-Hodgkin's lymphoma: a report from Iran. Asian Pac J Cancer Prev. 2016;17(3):1513-7. [http://journal.waocp.org/?sid=Entrez:PubMed&id=pmid:27039799&key=2016.17.3.1513 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27039799 PubMed]
-# '''FLYER:''' Poeschel V, Held G, Ziepert M, Witzens-Harig M, Holte H, Thurner L, Borchmann P, Viardot A, Soekler M, Keller U, Schmidt C, Truemper L, Mahlberg R, Marks R, Hoeffkes HG, Metzner B, Dierlamm J, Frickhofen N, Haenel M, Neubauer A, Kneba M, Merli F, Tucci A, de Nully Brown P, Federico M, Lengfelder E, di Rocco A, Trappe R, Rosenwald A, Berdel C, Maisenhoelder M, Shpilberg O, Amam J, Christofyllakis K, Hartmann F, Murawski N, Stilgenbauer S, Nickelsen M, Wulf G, Glass B, Schmitz N, Altmann B, Loeffler M, Pfreundschuh M; FLYER Trial Investigators; German Lymphoma Alliance. Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER): a randomised, phase 3, non-inferiority trial. Lancet. 2019 Dec 21;394(10216):2271-2281. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)33008-9/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/31868632 PubMed]
+#'''REMoDL-B:''' Davies A, Cummin TE, Barrans S, Maishman T, Mamot C, Novak U, Caddy J, Stanton L, Kazmi-Stokes S, McMillan A, Fields P, Pocock C, Collins GP, Stephens R, Cucco F, Clipson A, Sha C, Tooze R, Care MA, Griffiths G, Du MQ, Westhead DR, Burton C, Johnson PWM. Gene-expression profiling of bortezomib added to standard chemoimmunotherapy for diffuse large B-cell lymphoma (REMoDL-B): an open-label, randomised, phase 3 trial. Lancet Oncol. 2019 May;20(5):649-662. Epub 2019 Apr 1. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30935-5/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494978/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/30948276 PubMed]
+#'''FLYER:''' Poeschel V, Held G, Ziepert M, Witzens-Harig M, Holte H, Thurner L, Borchmann P, Viardot A, Soekler M, Keller U, Schmidt C, Truemper L, Mahlberg R, Marks R, Hoeffkes HG, Metzner B, Dierlamm J, Frickhofen N, Haenel M, Neubauer A, Kneba M, Merli F, Tucci A, de Nully Brown P, Federico M, Lengfelder E, di Rocco A, Trappe R, Rosenwald A, Berdel C, Maisenhoelder M, Shpilberg O, Amam J, Christofyllakis K, Hartmann F, Murawski N, Stilgenbauer S, Nickelsen M, Wulf G, Glass B, Schmitz N, Altmann B, Loeffler M, Pfreundschuh M; FLYER Trial Investigators; German Lymphoma Alliance. Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER): a randomised, phase 3, non-inferiority trial. Lancet. 2019 Dec 21;394(10216):2271-2281. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)33008-9/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/31868632 PubMed]
 ==R-CHOP (Rituximab Hycela) {{#subobject:98gxb2|Regimen=1}}==
@@ Line 844: / Line 905: @@
 R-CHOP: '''<u>R</u>'''ituximab Hycela, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisolone
 ===Example orders===
 *[[Example orders for R-CHOP in lymphoma]]
 ===Regimen {{#subobject:8a0576|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://www.haematologica.org/content/102/11/1913 Lugtenburg et al. 2017 (MabEase)]
 |2012-NR
-|style="background-color:#1a9851"|Phase III (E-RT-switch-ic)
+| style="background-color:#1a9851" |Phase III (E-RT-switch-ic)
 |[[#R-CHOP|R-CHOP]]
-|style="background-color:#d9ef8b"|Might have superior CR rate
+| style="background-color:#d9ef8b" |Might have superior CR rate
 |-
 |}
 ''Note: the details for CHOP are not available in the manuscript or supplement; we have reproduced common CHOP dosing, here. For patients achieving CR after cycle 4, the CHOP could be omitted after cycle 6.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] as follows:
 **Cycle 1: 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 875: / Line 938: @@
 ===References===
-# '''MabEase:''' Lugtenburg P, Avivi I, Berenschot H, Ilhan O, Marolleau JP, Nagler A, Rueda A, Tani M, Turgut M, Osborne S, Smith R, Pfreundschuh M. Efficacy and safety of subcutaneous and intravenous rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in first-line diffuse large B-cell lymphoma: the randomized MabEase study. Haematologica. 2017 Nov;102(11):1913-1922. Epub 2017 Sep 21. [http://www.haematologica.org/content/102/11/1913 link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28935843 PubMed]
+#'''MabEase:''' Lugtenburg P, Avivi I, Berenschot H, Ilhan O, Marolleau JP, Nagler A, Rueda A, Tani M, Turgut M, Osborne S, Smith R, Pfreundschuh M. Efficacy and safety of subcutaneous and intravenous rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in first-line diffuse large B-cell lymphoma: the randomized MabEase study. Haematologica. 2017 Nov;102(11):1913-1922. Epub 2017 Sep 21. [http://www.haematologica.org/content/102/11/1913 link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28935843 PubMed]
 ==R-CHOP-14 {{#subobject:fc3bde|Regimen=1}}==
@@ Line 887: / Line 951: @@
 ===Regimen variant #1, prednisone 40 mg/m<sup>2</sup>, 4 to 6 cycles {{#subobject:6ec36f|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://www.bloodjournal.org/content/131/2/174.long Lamy et al. 2017 (LYSA/GOELAMS 02-03)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 903: / Line 968: @@
 '''14-day cycle for 4 to 6 cycles'''
 ====Subsequent treatment====
 *[[#Observation|Observation]] versus [[#Radiation_therapy|IFRT]] x 40 Gy
 ===Regimen variant #2, prednisone 40 mg/m<sup>2</sup>, 8 cycles {{#subobject:6ec36f|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70122-0/fulltext Delarue et al. 2013 (LNH03-6B)]
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#1a9851" |Phase III (E-esc)
 |[[#R-CHOP|R-CHOP21]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of EFS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 |-
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 926: / Line 993: @@
 ====Supportive medications====
 *ONE of the following, "according to the treating doctor's decision, fulfilling existing guidelines and product labelling at that time."
 **[[Filgrastim (Neupogen)|Granulocyte colony-stimulating factor]]
 **[[Pegfilgrastim (Neulasta)|Pegylated G-CSF]]
 '''14-day cycle for 8 cycles'''
 ====CNS prophylaxis====
 *[[Methotrexate (MTX)]] 15 mg IT once on day 1
@@ Line 939: / Line 1,008: @@
 ===Regimen variant #3, prednisone 100 mg, BSA-based vincristine, standard-dose IV rituximab {{#subobject:9cab31|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-!style="width: 20%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116833/ Seymour et al. 2014 (MAIN)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |RA-CHOP-14
-|style="background-color:#ffffbf"|Did not meet secondary endpoint of PFS
+| style="background-color:#ffffbf" |Did not meet secondary endpoint of PFS
 | style="background-color:#1a9850" |Better cardiac safety
 |-
 |[https://ascopubs.org/doi/full/10.1200/JCO.2016.67.2980 Cortelazzo et al. 2016]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |R-HDS
-|style="background-color:#ffffbf"|Did not meet primary endpoint of EFS36
+| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS36
 |
 |-
-|rowspan=2|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30444-8/fulltext Chiappella et al. 2017 (DLCL04)]
+| rowspan="2" |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30444-8/fulltext Chiappella et al. 2017 (DLCL04)]
-|rowspan=2 style="background-color:#1a9851"|Phase III (C)
+| rowspan="2" style="background-color:#1a9851" |Phase III (C)
 |1. [[#R-MegaCHOP-14|R-MegaCHOP-14]]
-|style="background-color:#d3d3d3"|Not reported
+| style="background-color:#d3d3d3" |Not reported
 |
 |-
 |2. R-CHOP-14, then R-MAD, then BEAM, then auto HSCT<br> 3. R-MegaCHOP-14, then R-MAD, then BEAM, then auto HSCT
-|style="background-color:#ffffbf"|Did not meet primary endpoint of FFS24
+| style="background-color:#ffffbf" |Did not meet primary endpoint of FFS24
 |
 |-
@@ Line 970: / Line 1,039: @@
 ''Note: in MAIN, CHOP-14 was given for 6 cycles and rituximab for 8 cycles. In Cortelazzo et al. 2016, there is no cap on the vincristine dose, and there is also a discrepancy between the prednisone dose in the body of the manuscript and that in the appendix Figure A1; these discrepancies were clarified by the corresponding author in January 2017. In the abstract of DLCL04, there is no cap on vincristine.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 977: / Line 1,047: @@
 ====Supportive medications====
 *ONE of the following:
 **[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 7 to 11
@@ Line 985: / Line 1,056: @@
 ===Regimen variant #4, prednisone 100 mg, BSA-based vincristine, high-dose IV rituximab {{#subobject:5fb2fa|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://meetinglibrary.asco.org/content/133133-144 Pfreundschuh et al. 2014 (SEXIE-R-CHOP-14)]
-|style="background-color:#1a9851"|Randomized Phase II (E-esc)
+| style="background-color:#1a9851" |Randomized Phase II (E-esc)
 |See below
 |TBD
@@ Line 998: / Line 1,069: @@
 ''Note: two arms were assessed; results are pending from this comparison. These higher doses were for males, only.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] by ONE of the following schedules:
 **Cycles 1 to 8: 500 mg/m<sup>2</sup> IV once on day 1
@@ Line 1,010: / Line 1,082: @@
 ===Regimen variant #5, prednisone 100 mg, flat dose vincristine, 2 cycles, with response adaptation {{#subobject:a01893|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://ascopubs.org/doi/full/10.1200/JCO.2017.76.8093 Dührsen et al. 2018 (PETAL)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |}
 ====Preceding treatment====
 *[[#Vincristine_.26_Prednisone|Pre-phase vincristine & prednisone]]
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 2
@@ Line 1,028: / Line 1,103: @@
 '''14-day cycle for 2 cycles'''
 ====Subsequent treatment====
 *PET-negative: R-CHOP x 4 (6 cycles total) versus R-CHOP x 4, then rituximab x 2
 *PET-positive: R-CHOP x 6 (8 cycles total) versus intensive Burkitt lymphoma protocol
@@ Line 1,033: / Line 1,109: @@
 ===Regimen variant #6, prednisone 100 mg, flat dose vincristine, 6 cycles, extended rituximab exposure {{#subobject:aae4db|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://jco.ascopubs.org/content/32/36/4127.full Pfreundschuh et al. 2014 (SMARTE-R-CHOP-14)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Preceding treatment====
 *[[#Vincristine_.26_Prednisone|Pre-phase vincristine & prednisone]]
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days -4, 0, 10, 29, 57, 99, 155, 239 (independent of CHOP cycles)
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 1,050: / Line 1,129: @@
 ====Supportive medications====
 *ONE of the following starting on day 4, to continue until count recovery:
 **[[Filgrastim (Neupogen)]]
@@ Line 1,056: / Line 1,136: @@
 '''14-day cycle for 6 cycles'''
 ====Subsequent treatment====
 *Patients with initial bulky disease ("lymphoma masses or conglomerates with a diameter greater than or equal to 7.5 cm) or extranodal involvement"): [[#Radiation_therapy|RT]] x 36 Gy
 ===Regimen variant #7, prednisone 100 mg, flat dose vincristine, 6-8 cycles {{#subobject:30c25c|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|rowspan=3 |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2808%2970002-0/fulltext Pfreundschuh et al. 2008 (RICOVER-60)]
+| rowspan="3" |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2808%2970002-0/fulltext Pfreundschuh et al. 2008 (RICOVER-60)]
-|rowspan=3 style="background-color:#1a9851"|Phase III (E-esc)
+| rowspan="3" style="background-color:#1a9851" |Phase III (E-esc)
 |1. [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP-14|CHOP-14]] x 6
-|style="background-color:#1a9850"|Superior OS
+| style="background-color:#1a9850" |Superior OS
 |-
 |2. [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP-14|CHOP-14]] x 8
-|style="background-color:#d3d3d3"|Not reported
+| style="background-color:#d3d3d3" |Not reported
 |-
 |3. R-CHOP-14 x 8
-|style="background-color:#d3d3d3"|Not reported
+| style="background-color:#d3d3d3" |Not reported
 |-
 |[https://ascopubs.org/doi/10.1200/JCO.2013.51.4505 Held et al. 2014 (RICOVER-noRTh)]
@@ Line 1,083: / Line 1,164: @@
 |}
 ====Preceding treatment====
 *RICOVER-60: [[#Vincristine_.26_Prednisone|Pre-phase vincristine & prednisone]]
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 1,092: / Line 1,176: @@
 ====Supportive medications====
 *ONE of the following starting on day 4, to continue until count recovery:
 **[[Filgrastim (Neupogen)]]
@@ Line 1,098: / Line 1,183: @@
 '''14-day cycle for 6 to 8 cycles (8 doses of rituximab regardless of total number of cycles)'''
 ====Subsequent treatment====
 *RICOVER-60: Patients with initial bulky disease ("lymphoma masses or conglomerates with a diameter greater than or equal to 7.5 cm) or extranodal involvement"): [[#Radiation_therapy|RT]] x 36 Gy
 *RICOVER-noRTh: [[#Radiation_therapy|RT]] x 36 Gy versus observation
 ===References===
-# '''RICOVER-60:''' Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, Reiser M, Nickenig C, Clemens M, Peter N, Bokemeyer C, Eimermacher H, Ho A, Hoffmann M, Mertelsmann R, Trümper L, Balleisen L, Liersch R, Metzner B, Hartmann F, Glass B, Poeschel V, Schmitz N, Ruebe C, Feller AC, Loeffler M; German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 2008 Feb;9(2):105-16. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2808%2970002-0/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18226581 PubMed]
-# '''Abstract:''' S. Le Gouill, N. J. Milpied, T. Lamy, V. Delwail, R. Gressin, D. Guyotat, G. L. Damaj, C. Foussard, G. Cartron, H. Maisonneuve, E. Deconinck, F. Dreyfus, E. Gyan, L. Sutton, N. Morineau, M. Alexis, F. Perry, M. Sauvezie. First-line rituximab (R) high-dose therapy (R-HDT) versus R-CHOP14 for young adults with diffuse large B-cell lymphoma: Preliminary results of the GOELAMS 075 prospective multicenter randomized trial. Journal of Clinical Oncology 29, no. 15_suppl (May 2011) 8003-8003. [https://ascopubs.org/doi/full/10.1200/jco.2011.29.15_suppl.8003 link to abstract]
+#'''RICOVER-60:''' Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, Reiser M, Nickenig C, Clemens M, Peter N, Bokemeyer C, Eimermacher H, Ho A, Hoffmann M, Mertelsmann R, Trümper L, Balleisen L, Liersch R, Metzner B, Hartmann F, Glass B, Poeschel V, Schmitz N, Ruebe C, Feller AC, Loeffler M; German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 2008 Feb;9(2):105-16. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2808%2970002-0/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18226581 PubMed]
-# '''LNH03-6B:''' Delarue R, Tilly H, Mounier N, Petrella T, Salles G, Thieblemont C, Bologna S, Ghesquières H, Hacini M, Fruchart C, Ysebaert L, Fermé C, Casasnovas O, Van Hoof A, Thyss A, Delmer A, Fitoussi O, Molina TJ, Haioun C, Bosly A. Dose-dense rituximab-CHOP compared with standard rituximab-CHOP in elderly patients with diffuse large B-cell lymphoma (the LNH03-6B study): a randomised phase 3 trial. Lancet Oncol. 2013 May;14(6):525-33. Epub 2013 Apr 9. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70122-0/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23578722 PubMed]
+#'''Abstract:''' S. Le Gouill, N. J. Milpied, T. Lamy, V. Delwail, R. Gressin, D. Guyotat, G. L. Damaj, C. Foussard, G. Cartron, H. Maisonneuve, E. Deconinck, F. Dreyfus, E. Gyan, L. Sutton, N. Morineau, M. Alexis, F. Perry, M. Sauvezie. First-line rituximab (R) high-dose therapy (R-HDT) versus R-CHOP14 for young adults with diffuse large B-cell lymphoma: Preliminary results of the GOELAMS 075 prospective multicenter randomized trial. Journal of Clinical Oncology 29, no. 15_suppl (May 2011) 8003-8003. [https://ascopubs.org/doi/full/10.1200/jco.2011.29.15_suppl.8003 link to abstract]
-# '''RICOVER-noRTh:''' Held G, Murawski N, Ziepert M, Fleckenstein J, Pöschel V, Zwick C, Bittenbring J, Hänel M, Wilhelm S, Schubert J, Schmitz N, Löffler M, Rübe C, Pfreundschuh M. Role of radiotherapy to bulky disease in elderly patients with aggressive B-cell lymphoma. J Clin Oncol. 2014 Apr 10;32(11):1112-8. Epub 2014 Feb 3. [https://ascopubs.org/doi/10.1200/JCO.2013.51.4505 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24493716 PubMed]
+#'''LNH03-6B:''' Delarue R, Tilly H, Mounier N, Petrella T, Salles G, Thieblemont C, Bologna S, Ghesquières H, Hacini M, Fruchart C, Ysebaert L, Fermé C, Casasnovas O, Van Hoof A, Thyss A, Delmer A, Fitoussi O, Molina TJ, Haioun C, Bosly A. Dose-dense rituximab-CHOP compared with standard rituximab-CHOP in elderly patients with diffuse large B-cell lymphoma (the LNH03-6B study): a randomised phase 3 trial. Lancet Oncol. 2013 May;14(6):525-33. Epub 2013 Apr 9. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70122-0/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23578722 PubMed]
-# '''Abstract:''' Michael Pfreundschuh, Gerhard Held, Samira Zeynalova, Carsten Zwick, Mathias Haenel, Lorenz Truemper, Martin H. Dreyling, Judith Dierlamm, Markus Loeffler, Norbert Schmitz, Niels Murawski, German High-Grad Non-Hodgkin Lymphoma Study Group (DSHNHL). Increased rituximab (R) doses and effect on risk of elderly male patients with aggressive CD20+ B-cell lymphomas: Results from the SEXIE-R-CHOP-14 trial of the DSHNHL. J Clin Oncol 32:5s, 2014 (suppl; abstr 8501) [http://meetinglibrary.asco.org/content/133133-144 link to original abstract]
+#'''RICOVER-noRTh:''' Held G, Murawski N, Ziepert M, Fleckenstein J, Pöschel V, Zwick C, Bittenbring J, Hänel M, Wilhelm S, Schubert J, Schmitz N, Löffler M, Rübe C, Pfreundschuh M. Role of radiotherapy to bulky disease in elderly patients with aggressive B-cell lymphoma. J Clin Oncol. 2014 Apr 10;32(11):1112-8. Epub 2014 Feb 3. [https://ascopubs.org/doi/10.1200/JCO.2013.51.4505 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24493716 PubMed]
-# '''MAIN:''' Seymour JF, Pfreundschuh M, Trnený M, Sehn LH, Catalano J, Csinady E, Moore N, Coiffier B; MAIN Study Investigators. R-CHOP with or without bevacizumab in patients with previously untreated diffuse large B-cell lymphoma: final MAIN study outcomes. Haematologica. 2014 Aug;99(8):1343-9. Epub 2014 Jun 3. [http://www.haematologica.org/content/99/8/1343.abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116833/ link to PMC article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24895339 PubMed]
+#'''Abstract:''' Michael Pfreundschuh, Gerhard Held, Samira Zeynalova, Carsten Zwick, Mathias Haenel, Lorenz Truemper, Martin H. Dreyling, Judith Dierlamm, Markus Loeffler, Norbert Schmitz, Niels Murawski, German High-Grad Non-Hodgkin Lymphoma Study Group (DSHNHL). Increased rituximab (R) doses and effect on risk of elderly male patients with aggressive CD20+ B-cell lymphomas: Results from the SEXIE-R-CHOP-14 trial of the DSHNHL. J Clin Oncol 32:5s, 2014 (suppl; abstr 8501) [http://meetinglibrary.asco.org/content/133133-144 link to original abstract]
-# '''SMARTE-R-CHOP-14:''' Pfreundschuh M, Poeschel V, Zeynalova S, Hänel M, Held G, Schmitz N, Viardot A, Dreyling MH, Hallek M, Mueller C, Wiesen MH, Witzens-Harig M, Truemper L, Keller U, Rixecker T, Zwick C, Murawski N. Optimization of rituximab for the treatment of diffuse large B-cell lymphoma (II): extended rituximab exposure time in the SMARTE-R-CHOP-14 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group. J Clin Oncol. 2014 Dec 20;32(36):4127-33. Epub 2014 Nov 17. Erratum in: J Clin Oncol. 2015 Jun 10;33(17):1991. [http://jco.ascopubs.org/content/32/36/4127.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25403207 PubMed]
+#'''MAIN:''' Seymour JF, Pfreundschuh M, Trnený M, Sehn LH, Catalano J, Csinady E, Moore N, Coiffier B; MAIN Study Investigators. R-CHOP with or without bevacizumab in patients with previously untreated diffuse large B-cell lymphoma: final MAIN study outcomes. Haematologica. 2014 Aug;99(8):1343-9. Epub 2014 Jun 3. [http://www.haematologica.org/content/99/8/1343.abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116833/ link to PMC article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24895339 PubMed]
+#'''SMARTE-R-CHOP-14:''' Pfreundschuh M, Poeschel V, Zeynalova S, Hänel M, Held G, Schmitz N, Viardot A, Dreyling MH, Hallek M, Mueller C, Wiesen MH, Witzens-Harig M, Truemper L, Keller U, Rixecker T, Zwick C, Murawski N. Optimization of rituximab for the treatment of diffuse large B-cell lymphoma (II): extended rituximab exposure time in the SMARTE-R-CHOP-14 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group. J Clin Oncol. 2014 Dec 20;32(36):4127-33. Epub 2014 Nov 17. Erratum in: J Clin Oncol. 2015 Jun 10;33(17):1991. [http://jco.ascopubs.org/content/32/36/4127.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25403207 PubMed]
 <!-- Presented in part at the 54th American Society of Hematology Annual Meeting, Atlanta, GA, December 8-11, 2012, and the 12th International Conference on Malignant Lymphoma, Lugano, Switzerland, June 19-22, 2013 -->
-# Cortelazzo S, Tarella C, Gianni AM, Ladetto M, Barbui AM, Rossi A, Gritti G, Corradini P, Di Nicola M, Patti C, Mulé A, Zanni M, Zoli V, Billio A, Piccin A, Negri G, Castellino C, Di Raimondo F, Ferreri AJ, Benedetti F, La Nasa G, Gini G, Trentin L, Frezzato M, Flenghi L, Falorio S, Chilosi M, Bruna R, Tabanelli V, Pileri S, Masciulli A, Delaini F, Boschini C, Rambaldi A. Randomized trial comparing R-CHOP versus high-dose sequential chemotherapy in high-risk patients with diffuse large B-cell lymphomas. J Clin Oncol. 2016 Nov 20;34(33):4015-4022. Epub 2016 Oct 31. [https://ascopubs.org/doi/full/10.1200/JCO.2016.67.2980 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28199143 PubMed]
+#Cortelazzo S, Tarella C, Gianni AM, Ladetto M, Barbui AM, Rossi A, Gritti G, Corradini P, Di Nicola M, Patti C, Mulé A, Zanni M, Zoli V, Billio A, Piccin A, Negri G, Castellino C, Di Raimondo F, Ferreri AJ, Benedetti F, La Nasa G, Gini G, Trentin L, Frezzato M, Flenghi L, Falorio S, Chilosi M, Bruna R, Tabanelli V, Pileri S, Masciulli A, Delaini F, Boschini C, Rambaldi A. Randomized trial comparing R-CHOP versus high-dose sequential chemotherapy in high-risk patients with diffuse large B-cell lymphomas. J Clin Oncol. 2016 Nov 20;34(33):4015-4022. Epub 2016 Oct 31. [https://ascopubs.org/doi/full/10.1200/JCO.2016.67.2980 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28199143 PubMed]
-# '''DLCL04:''' Chiappella A, Martelli M, Angelucci E, Brusamolino E, Evangelista A, Carella AM, Stelitano C, Rossi G, Balzarotti M, Merli F, Gaidano G, Pavone V, Rigacci L, Zaja F, D'Arco A, Cascavilla N, Russo E, Castellino A, Gotti M, Congiu AG, Cabras MG, Tucci A, Agostinelli C, Ciccone G, Pileri SA, Vitolo U. Rituximab-dose-dense chemotherapy with or without high-dose chemotherapy plus autologous stem-cell transplantation in high-risk diffuse large B-cell lymphoma (DLCL04): final results of a multicentre, open-label, randomised, controlled, phase 3 study. Lancet Oncol. 2017 Aug;18(8):1076-1088. Epub 2017 Jun 28. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30444-8/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28668386 PubMed]
+#'''DLCL04:''' Chiappella A, Martelli M, Angelucci E, Brusamolino E, Evangelista A, Carella AM, Stelitano C, Rossi G, Balzarotti M, Merli F, Gaidano G, Pavone V, Rigacci L, Zaja F, D'Arco A, Cascavilla N, Russo E, Castellino A, Gotti M, Congiu AG, Cabras MG, Tucci A, Agostinelli C, Ciccone G, Pileri SA, Vitolo U. Rituximab-dose-dense chemotherapy with or without high-dose chemotherapy plus autologous stem-cell transplantation in high-risk diffuse large B-cell lymphoma (DLCL04): final results of a multicentre, open-label, randomised, controlled, phase 3 study. Lancet Oncol. 2017 Aug;18(8):1076-1088. Epub 2017 Jun 28. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30444-8/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28668386 PubMed]
-# '''MabEase:''' Lugtenburg P, Avivi I, Berenschot H, Ilhan O, Marolleau JP, Nagler A, Rueda A, Tani M, Turgut M, Osborne S, Smith R, Pfreundschuh M. Efficacy and safety of subcutaneous and intravenous rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in first-line diffuse large B-cell lymphoma: the randomized MabEase study. Haematologica. 2017 Nov;102(11):1913-1922. Epub 2017 Sep 21. [http://www.haematologica.org/content/102/11/1913 link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28935843 PubMed]
+#'''MabEase:''' Lugtenburg P, Avivi I, Berenschot H, Ilhan O, Marolleau JP, Nagler A, Rueda A, Tani M, Turgut M, Osborne S, Smith R, Pfreundschuh M. Efficacy and safety of subcutaneous and intravenous rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in first-line diffuse large B-cell lymphoma: the randomized MabEase study. Haematologica. 2017 Nov;102(11):1913-1922. Epub 2017 Sep 21. [http://www.haematologica.org/content/102/11/1913 link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28935843 PubMed]
-# Lamy T, Damaj G, Soubeyran P, Gyan E, Cartron G, Bouabdallah K, Gressin R, Cornillon J, Banos A, Le Du K, Benchalal M, Moles MP, Le Gouill S, Fleury J, Godmer P, Maisonneuve H, Deconinck E, Houot R, Laribi K, Marolleau JP, Tournilhac O, Branger B, Devillers A, Vuillez JP, Fest T, Colombat P, Costes V, Szablewski V, Béné MC, Delwail V; LYSA Group. R-CHOP 14 with or without radiotherapy in nonbulky limited-stage diffuse large B-cell lymphoma. Blood. 2018 Jan 11;131(2):174-181. Epub 2017 Oct 23. [http://www.bloodjournal.org/content/131/2/174.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29061568 PubMed]
+#Lamy T, Damaj G, Soubeyran P, Gyan E, Cartron G, Bouabdallah K, Gressin R, Cornillon J, Banos A, Le Du K, Benchalal M, Moles MP, Le Gouill S, Fleury J, Godmer P, Maisonneuve H, Deconinck E, Houot R, Laribi K, Marolleau JP, Tournilhac O, Branger B, Devillers A, Vuillez JP, Fest T, Colombat P, Costes V, Szablewski V, Béné MC, Delwail V; LYSA Group. R-CHOP 14 with or without radiotherapy in nonbulky limited-stage diffuse large B-cell lymphoma. Blood. 2018 Jan 11;131(2):174-181. Epub 2017 Oct 23. [http://www.bloodjournal.org/content/131/2/174.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29061568 PubMed]
-# '''PETAL:''' Dührsen U, Müller S, Hertenstein B, Thomssen H, Kotzerke J, Mesters R, Berdel WE, Franzius C, Kroschinsky F, Weckesser M, Kofahl-Krause D, Bengel FM, Dürig J, Matschke J, Schmitz C, Pöppel T, Ose C, Brinkmann M, La Rosée P, Freesmeyer M, Hertel A, Höffkes HG, Behringer D, Prange-Krex G, Wilop S, Krohn T, Holzinger J, Griesshammer M, Giagounidis A, Raghavachar A, Maschmeyer G, Brink I, Bernhard H, Haberkorn U, Gaska T, Kurch L, van Assema DME, Klapper W, Hoelzer D, Geworski L, Jöckel KH, Scherag A, Bockisch A, Rekowski J, Hüttmann A; PETAL Trial Investigators. Positron emission tomography-guided therapy of aggressive non-Hodgkin lymphomas (PETAL): a multicenter, randomized phase III trial. J Clin Oncol. 2018 Jul 10;36(20):2024-2034. Epub 2018 May 11. [https://ascopubs.org/doi/full/10.1200/JCO.2017.76.8093 link to original article] '''contains verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/29750632 PubMed]
+#'''PETAL:''' Dührsen U, Müller S, Hertenstein B, Thomssen H, Kotzerke J, Mesters R, Berdel WE, Franzius C, Kroschinsky F, Weckesser M, Kofahl-Krause D, Bengel FM, Dürig J, Matschke J, Schmitz C, Pöppel T, Ose C, Brinkmann M, La Rosée P, Freesmeyer M, Hertel A, Höffkes HG, Behringer D, Prange-Krex G, Wilop S, Krohn T, Holzinger J, Griesshammer M, Giagounidis A, Raghavachar A, Maschmeyer G, Brink I, Bernhard H, Haberkorn U, Gaska T, Kurch L, van Assema DME, Klapper W, Hoelzer D, Geworski L, Jöckel KH, Scherag A, Bockisch A, Rekowski J, Hüttmann A; PETAL Trial Investigators. Positron emission tomography-guided therapy of aggressive non-Hodgkin lymphomas (PETAL): a multicenter, randomized phase III trial. J Clin Oncol. 2018 Jul 10;36(20):2024-2034. Epub 2018 May 11. [https://ascopubs.org/doi/full/10.1200/JCO.2017.76.8093 link to original article] '''contains verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/29750632 PubMed]
 ==R-CHOP-14 (Prednisolone) {{#subobject:fc3zyb|Regimen=1}}==
@@ Line 1,124: / Line 1,211: @@
 ===Regimen {{#subobject:8136b1|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)60313-X/fulltext Cunningham et al. 2013 (UK NCRI R-CHOP14v21)]
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#1a9851" |Phase III (E-esc)
 |[[#R-CHOP_.28Prednisolone.29|R-CHOP-21]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] as follows:
@@ Line 1,148: / Line 1,236: @@
 ====CNS prophylaxis====
 Per investigator discretion, but Cunningham et al. 2013 recommended that patients who had involvement of the "bone marrow, peripheral blood, nasal or paranasal sinuses, orbit, and testis" (they probably intended to say "or testis") receive:
 *[[Methotrexate (MTX)]] 12.5 mg IT "for the first three cycles of treatment, administered as per local guidelines." No other details given.
 ====Supportive medications====
 *[[Lenograstim (Granocyte)]] (dose/route not specified) given on days 4 to 12
 *[[Allopurinol (Zyloprim)]] 300 mg PO once per day during cycle 1
@@ Line 1,158: / Line 1,248: @@
 ===References===
-# '''UK NCRI R-CHOP14v21:''' Cunningham D, Hawkes EA, Jack A, Qian W, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford JA, McMillan A, Davies J, Turner D, Kruger A, Johnson P, Gambell J, Linch D. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet. 2013 May 25;381(9880):1817-26. Epub 2013 Apr 22. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)60313-X/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23615461 PubMed]
+#'''UK NCRI R-CHOP14v21:''' Cunningham D, Hawkes EA, Jack A, Qian W, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford JA, McMillan A, Davies J, Turner D, Kruger A, Johnson P, Gambell J, Linch D. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet. 2013 May 25;381(9880):1817-26. Epub 2013 Apr 22. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)60313-X/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23615461 PubMed]
 ==R-CHOP-14 (Rituximab Hycela) {{#subobject:fcbace|Regimen=1}}==
@@ Line 1,169: / Line 1,260: @@
 ===Regimen {{#subobject:dc3888|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://www.haematologica.org/content/102/11/1913 Lugtenburg et al. 2017 (MabEase)]
 |2012-NR
-|style="background-color:#1a9851"|Phase III (E-RT-switch-ic)
+| style="background-color:#1a9851" |Phase III (E-RT-switch-ic)
 |[[#R-CHOP-14|R-CHOP-14]]
-|style="background-color:#d9ef8b"|Might have superior CR rate
+| style="background-color:#d9ef8b" |Might have superior CR rate
 |-
 |}
 ''Note: the details for CHOP-14 are not available in the manuscript or supplement; we have reproduced common CHOP-14 dosing, here. For patients achieving CR after cycle 4, the CHOP-14 could be omitted after cycle 6.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] as follows:
 **Cycle 1: 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 1,194: / Line 1,286: @@
 ====Supportive medications====
 *ONE of the following:
 **[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 7 to 11
@@ Line 1,201: / Line 1,294: @@
 ===References===
-# '''MabEase:''' Lugtenburg P, Avivi I, Berenschot H, Ilhan O, Marolleau JP, Nagler A, Rueda A, Tani M, Turgut M, Osborne S, Smith R, Pfreundschuh M. Efficacy and safety of subcutaneous and intravenous rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in first-line diffuse large B-cell lymphoma: the randomized MabEase study. Haematologica. 2017 Nov;102(11):1913-1922. Epub 2017 Sep 21. [http://www.haematologica.org/content/102/11/1913 link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28935843 PubMed]
+#'''MabEase:''' Lugtenburg P, Avivi I, Berenschot H, Ilhan O, Marolleau JP, Nagler A, Rueda A, Tani M, Turgut M, Osborne S, Smith R, Pfreundschuh M. Efficacy and safety of subcutaneous and intravenous rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in first-line diffuse large B-cell lymphoma: the randomized MabEase study. Haematologica. 2017 Nov;102(11):1913-1922. Epub 2017 Sep 21. [http://www.haematologica.org/content/102/11/1913 link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28935843 PubMed]
 ==R-Hyper-CVAD/R-MA {{#subobject:432427|Regimen=1}}==
@@ Line 1,212: / Line 1,306: @@
 ===Protocol {{#subobject:b7ff27|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278952/ Oki et al. 2013 (MDACC 2005-0054)]
-|style="background-color:#1a9851"|Randomized Phase II (E-esc)
+| style="background-color:#1a9851" |Randomized Phase II (E-esc)
 |[[#R-CHOP|R-CHOP]]
-|style="background-color:#91cf60"|Seems to have increased CRR
+| style="background-color:#91cf60" |Seems to have increased CRR
 |-
 |}
 ''Intended for high-risk DLBCL (IPI greater than or equal to 3). The authors report "excellent outcome" in patients less than or equal to 45 years old, however patients greater than 45 years old had "unacceptable mortality."''
 ====Chemotherapy, part A (cycles 1, 3, 5)====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 300 mg/m<sup>2</sup> IV every 12 hours on days 1 to 3 (total dose per cycle: 1800 mg/m<sup>2</sup>)
 *[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 5 & 12
 *[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 5
 *[[Dexamethasone (Decadron)]] 40 mg IV or PO once per day on days 2 to 5
 ====Supportive medications====
 *[[Mesna (Mesnex)]] 600 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 1 (total dose per cycle: 1800 mg/m<sup>2</sup>)
 *[[Filgrastim (Neupogen)]] or [[Pegfilgrastim (Neulasta)]] starting 24 to 48 hours after completion of chemotherapy
@@ Line 1,239: / Line 1,335: @@
 ====Dose modifications====
 *[[Vincristine (Oncovin)]] reduced once by 50% for NCI common toxicity criteria Grade 2+ peripheral neuropathy, omitted if Grade 2+ peripheral neuropathy persists
 *[[Doxorubicin (Adriamycin)]] and [[Cyclophosphamide (Cytoxan)]] reduced by 20% in subsequent A cycles if neutropenic fever occurs, grade 3/4 non-hematological toxicity, or ANC less than 750/uL or platelet count less than 75 × 10<sup>9</sup>/L on day 21
 '''Next cycle to start once ANC is greater than or equal to 1000/uL and platelet count is greater than or equal to 100 × 10<sup>9</sup>/L.'''
@@ Line 1,247: / Line 1,344: @@
 ====Chemotherapy, part B (cycles 2, 4, 6)====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Methotrexate (MTX)]] 200 mg/m<sup>2</sup> IV over 2 hours once on day 1, then 800 mg/m<sup>2</sup> IV over 22 hours (total dose per cycle: 1000 mg/m<sup>2</sup>)
@@ Line 1,252: / Line 1,350: @@
 ====Supportive medications====
 *[[Folinic acid (Leucovorin)]] (dose/timing not specified) until serum methotrexate level less than 100 nmol/L
 *[[Sodium bicarbonate]] 1300 mg PO twice per day until methotrexate level less than 100 nmol/L
@@ Line 1,260: / Line 1,359: @@
 ====Dose modifications====
 *[[Methotrexate (MTX)]] reduced by 25% in subsequent B cycles if neutropenic fever occurs, grade 3/4 non-hematological toxicity, or ANC less than 750/uL or platelet count less than 75 × 10<sup>9</sup>/L on day 21
 *[[Cytarabine (Ara-C)]] reduced by 33% in subsequent B cycles if neutropenic fever occurs, grade 3/4 non-hematological toxicity, or ANC less than 750/uL or platelet count less than 75 × 10<sup>9</sup>/L on day 21
@@ Line 1,269: / Line 1,369: @@
 ===References===
-# Oki Y, Westin JR, Vega F, Chuang H, Fowler N, Neelapu S, Hagemeister FB, McLaughlin P, Kwak LW, Romaguera JE, Fanale M, Younes A, Rodriguez MA, Orlowski RZ, Wang M, Ouzounian ST, Samaniego F, Fayad L. Prospective phase II study of rituximab with alternating cycles of hyper-CVAD and high-dose methotrexate with cytarabine for young patients with high-risk diffuse large B-cell lymphoma. Br J Haematol. 2013 Dec;163(5):611-20. Epub 2013 Oct 1. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.12585/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278952/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24117234 PubMed]
+#Oki Y, Westin JR, Vega F, Chuang H, Fowler N, Neelapu S, Hagemeister FB, McLaughlin P, Kwak LW, Romaguera JE, Fanale M, Younes A, Rodriguez MA, Orlowski RZ, Wang M, Ouzounian ST, Samaniego F, Fayad L. Prospective phase II study of rituximab with alternating cycles of hyper-CVAD and high-dose methotrexate with cytarabine for young patients with high-risk diffuse large B-cell lymphoma. Br J Haematol. 2013 Dec;163(5):611-20. Epub 2013 Oct 1. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.12585/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278952/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24117234 PubMed]
 <!-- Prior publication: Poster presentation at the 2014 annual meeting of the American Society of Hematology (Howlett C, Landsburg DJ, Chong EA, Snedecor SJ, Schuster SJ, Green TM, Cohen JB, Svoboda J, Nasta SD, Feldman T, Rago R, Land D, Walsh KM, Goy A, Mato AR. Front-line, dose-escalated immunochemotherapy is associated with a significant PFS (but not OS) advantage in 401 patients (pts) with double-hit lymphomas (DHL): A systematic review and meta-analysis. Blood, 124, abst 3056). -->
-# '''Retrospective:''' Howlett C, Snedecor SJ, Landsburg DJ, Svoboda J, Chong EA, Schuster SJ, Nasta SD, Feldman T, Rago A, Walsh KM, Weber S, Goy A, Mato A. Front-line, dose-escalated immunochemotherapy is associated with a significant progression-free survival advantage in patients with double-hit lymphomas: a systematic review and meta-analysis. Br J Haematol. 2015 Aug;170(4):504-14. Epub 2015 Apr 24. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13463/full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25907897 PubMed]
+#'''Retrospective:''' Howlett C, Snedecor SJ, Landsburg DJ, Svoboda J, Chong EA, Schuster SJ, Nasta SD, Feldman T, Rago A, Walsh KM, Weber S, Goy A, Mato A. Front-line, dose-escalated immunochemotherapy is associated with a significant progression-free survival advantage in patients with double-hit lymphomas: a systematic review and meta-analysis. Br J Haematol. 2015 Aug;170(4):504-14. Epub 2015 Apr 24. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13463/full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25907897 PubMed]
 ==R-MegaCHOP-14 {{#subobject:8e9669|Regimen=1}}==
@@ Line 1,282: / Line 1,383: @@
 ===Regimen {{#subobject:6d7b6c|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|rowspan=2|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30444-8/fulltext Chiappella et al. 2017 (DLCL04)]
+| rowspan="2" |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30444-8/fulltext Chiappella et al. 2017 (DLCL04)]
-|rowspan=2 style="background-color:#1a9851"|Phase III (E-esc)
+| rowspan="2" style="background-color:#1a9851" |Phase III (E-esc)
 |1. [[#R-CHOP-14|R-CHOP-14]]
-|style="background-color:#d3d3d3"|Not reported
+| style="background-color:#d3d3d3" |Not reported
 |-
 |2. R-CHOP-14, then R-MAD, then BEAM, then auto HSCT<br> 3. R-MegaCHOP-14, then R-MAD, then BEAM, then auto HSCT
-|style="background-color:#ffffbf"|Did not meet primary endpoint of FFS24
+| style="background-color:#ffffbf" |Did not meet primary endpoint of FFS24
 |-
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV once on day 1
@@ Line 1,306: / Line 1,408: @@
 ===References===
-# Chiappella A, Martelli M, Angelucci E, Brusamolino E, Evangelista A, Carella AM, Stelitano C, Rossi G, Balzarotti M, Merli F, Gaidano G, Pavone V, Rigacci L, Zaja F, D'Arco A, Cascavilla N, Russo E, Castellino A, Gotti M, Congiu AG, Cabras MG, Tucci A, Agostinelli C, Ciccone G, Pileri SA, Vitolo U. Rituximab-dose-dense chemotherapy with or without high-dose chemotherapy plus autologous stem-cell transplantation in high-risk diffuse large B-cell lymphoma (DLCL04): final results of a multicentre, open-label, randomised, controlled, phase 3 study. Lancet Oncol. 2017 Aug;18(8):1076-1088. Epub 2017 Jun 28. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30444-8/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28668386 PubMed]
+#Chiappella A, Martelli M, Angelucci E, Brusamolino E, Evangelista A, Carella AM, Stelitano C, Rossi G, Balzarotti M, Merli F, Gaidano G, Pavone V, Rigacci L, Zaja F, D'Arco A, Cascavilla N, Russo E, Castellino A, Gotti M, Congiu AG, Cabras MG, Tucci A, Agostinelli C, Ciccone G, Pileri SA, Vitolo U. Rituximab-dose-dense chemotherapy with or without high-dose chemotherapy plus autologous stem-cell transplantation in high-risk diffuse large B-cell lymphoma (DLCL04): final results of a multicentre, open-label, randomised, controlled, phase 3 study. Lancet Oncol. 2017 Aug;18(8):1076-1088. Epub 2017 Jun 28. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30444-8/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28668386 PubMed]
 ==R-miniCEOP {{#subobject:cd6200|Regimen=1}}==
@@ Line 1,317: / Line 1,420: @@
 ===Regimen {{#subobject:41cd4b|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.tandfonline.com/doi/full/10.3109/10428194.2011.621565 Merli et al. 2012 (ANZINTER3)]
-|style="background-color:#1a9851"|Phase III (E-de-esc)
+| style="background-color:#1a9851" |Phase III (E-de-esc)
 |[[#R-CHOP|R-CHOP]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of EFS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 |-
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 1,336: / Line 1,440: @@
 ====Supportive medications====
 *Prophylactic [[:Category:Granulocyte colony-stimulating factors|G-CSF]] used for persisting grade 4 neutropenia or febrile neutropenia.
 *[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Cotrimoxazole]] (dose/route/schedule not specified) prophylaxis.
@@ Line 1,342: / Line 1,447: @@
 '''21-day cycle for 6 cycles'''
 ====Subsequent treatment====
 *Patients with initial bulky disease and/or partially responding sites received [[#Radiation_therapy|radiothearpy]]
 ===References===
-# '''ANZINTER3:''' Merli F, Luminari S, Rossi G, Mammi C, Marcheselli L, Tucci A, Ilariucci F, Chiappella A, Musso M, Di Rocco A, Stelitano C, Alvarez I, Baldini L, Mazza P, Salvi F, Arcari A, Fragasso A, Gobbi PG, Liberati AM, Federico M. Cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab versus epirubicin, cyclophosphamide, vinblastine, prednisone and rituximab for the initial treatment of elderly "fit" patients with diffuse large B-cell lymphoma: results from the ANZINTER3 trial of the Intergruppo Italiano Linfomi. Leuk Lymphoma. 2012 Apr;53(4):581-8. Epub 2011 Nov 15. [https://www.tandfonline.com/doi/full/10.3109/10428194.2011.621565 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21895543 PubMed]
+#'''ANZINTER3:''' Merli F, Luminari S, Rossi G, Mammi C, Marcheselli L, Tucci A, Ilariucci F, Chiappella A, Musso M, Di Rocco A, Stelitano C, Alvarez I, Baldini L, Mazza P, Salvi F, Arcari A, Fragasso A, Gobbi PG, Liberati AM, Federico M. Cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab versus epirubicin, cyclophosphamide, vinblastine, prednisone and rituximab for the initial treatment of elderly "fit" patients with diffuse large B-cell lymphoma: results from the ANZINTER3 trial of the Intergruppo Italiano Linfomi. Leuk Lymphoma. 2012 Apr;53(4):581-8. Epub 2011 Nov 15. [https://www.tandfonline.com/doi/full/10.3109/10428194.2011.621565 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21895543 PubMed]
 =Untreated, non-randomized or retrospective data=
@@ Line 1,357: / Line 1,464: @@
 ===Regimen variant #1, 90 mg/m<sup>2</sup> {{#subobject:da8206|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063684/ Park et al. 2016 (LCCC 1011)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''Note: this dosing was intended for patients with [[Performance_status#ECOG_performance_status_.28WHO.2FGOG.2FZubrod_score.29|ECOG PS]] = 3 at baseline.''
 ====Chemotherapy====
 *[[Bendamustine]] 90 mg/m<sup>2</sup> IV once per day on days 1 & 2, '''given first on day 1'''
 **Dose increased to 120 mg/m<sup>2</sup> if ECOG PS improved to less than or equal to 2 after 3 cycles
@@ Line 1,374: / Line 1,482: @@
 ===Regimen variant #2, 120 mg/m<sup>2</sup> {{#subobject:2f4cc2|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063684/ Park et al. 2016 (LCCC 1011)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Chemotherapy====
 *[[Bendamustine]] 120 mg/m<sup>2</sup> IV once per day on days 1 & 2, '''given first on day 1'''
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1, '''given second'''
@@ Line 1,388: / Line 1,497: @@
 ===References===
-# '''LCCC 1011:''' Park SI, Grover NS, Olajide O, Asch AS, Wall JG, Richards KL, Sobol AL, Deal AM, Ivanova A, Foster MC, Muss HB, Shea TC. A phase II trial of bendamustine in combination with rituximab in older patients with previously untreated diffuse large B-cell lymphoma. Br J Haematol. 2016 Oct;175(2):281-289. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.14232/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063684/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27448091 PubMed]
+#'''LCCC 1011:''' Park SI, Grover NS, Olajide O, Asch AS, Wall JG, Richards KL, Sobol AL, Deal AM, Ivanova A, Foster MC, Muss HB, Shea TC. A phase II trial of bendamustine in combination with rituximab in older patients with previously untreated diffuse large B-cell lymphoma. Br J Haematol. 2016 Oct;175(2):281-289. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.14232/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063684/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27448091 PubMed]
 ==Helicobacter pylori eradication therapy {{#subobject:be3ef5|Regimen=1}}==
@@ Line 1,398: / Line 1,508: @@
 ===Regimen variant #1, before 1996 {{#subobject:6a2469|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://www.bloodjournal.org/content/119/21/4838.long Kuo et al. 2012]
@@ Line 1,407: / Line 1,517: @@
 ''Note: This regimen is intended for the treatment of gastric DLBCL only; H. pylori eradication would not be an appropriate treatment for systemic DLBCL.''
 ====Antibiotic therapy====
 *[[Amoxicillin]] 500 mg PO every 6 hours
 *[[Metronidazole (Flagyl)]] 250 mg PO every 6 hours
@@ Line 1,417: / Line 1,528: @@
 ===Regimen variant #2, after 1996 {{#subobject:6a3969|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://www.bloodjournal.org/content/119/21/4838.long Kuo et al. 2012]
@@ Line 1,426: / Line 1,537: @@
 ''Note: This regimen is intended for the treatment of gastric DLBCL only; H. pylori eradication would not be an appropriate treatment for systemic DLBCL.''
 ====Antibiotic therapy====
 *[[Amoxicillin]] 500 mg PO every 6 hours
 *[[Clarithromycin (Biaxin)]] 500 mg PO twice per day
@@ Line 1,433: / Line 1,545: @@
 ===References===
-# Kuo SH, Yeh KH, Wu MS, Lin CW, Hsu PN, Wang HP, Chen LT, Cheng AL. Helicobacter pylori eradication therapy is effective in the treatment of early-stage H pylori-positive gastric diffuse large B-cell lymphomas. Blood. 2012 May 24;119(21):4838-44. Epub 2012 Mar 7. [http://www.bloodjournal.org/content/119/21/4838.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22403257 PubMed]
+#Kuo SH, Yeh KH, Wu MS, Lin CW, Hsu PN, Wang HP, Chen LT, Cheng AL. Helicobacter pylori eradication therapy is effective in the treatment of early-stage H pylori-positive gastric diffuse large B-cell lymphomas. Blood. 2012 May 24;119(21):4838-44. Epub 2012 Mar 7. [http://www.bloodjournal.org/content/119/21/4838.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22403257 PubMed]
 ==O-miniCHOP {{#subobject:652b56|Regimen=1}}==
@@ Line 1,444: / Line 1,557: @@
 ===Regimen {{#subobject:6d1193|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(16)30171-5/fulltext Peyrade et al. 2017 (LYSA LNH09-7B)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Preceding treatment====
 *[[#Vincristine_.26_Prednisone|Pre-phase vincristine & prednisone]]
 ====Chemotherapy====
 *[[Ofatumumab (Arzerra)]] 1000 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 400 mg/m<sup>2</sup> IV once on day 1
@@ Line 1,461: / Line 1,577: @@
 ====Supportive medications====
 *[[Acetaminophen (Tylenol)]] 1000 mg PO once on day 1, prior to [[Ofatumumab (Arzerra)]]
 *[[Diphenhydramine (Benadryl)]] 50 mg (route not specified) once on day 1, prior to [[Ofatumumab (Arzerra)]]
@@ Line 1,467: / Line 1,584: @@
 ===References===
-# Peyrade F, Bologna S, Delwail V, Emile JF, Pascal L, Fermé C, Schiano JM, Coiffier B, Corront B, Farhat H, Fruchart C, Ghesquieres H, Macro M, Tilly H, Choufi B, Delarue R, Fitoussi O, Gabarre J, Haioun C, Jardin F. Combination of ofatumumab and reduced-dose CHOP for diffuse large B-cell lymphomas in patients aged 80 years or older: an open-label, multicentre, single-arm, phase 2 trial from the LYSA group. Lancet Haematol. 2017 Jan;4(1):e46-e55. [https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(16)30171-5/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28041583 PubMed]
+#Peyrade F, Bologna S, Delwail V, Emile JF, Pascal L, Fermé C, Schiano JM, Coiffier B, Corront B, Farhat H, Fruchart C, Ghesquieres H, Macro M, Tilly H, Choufi B, Delarue R, Fitoussi O, Gabarre J, Haioun C, Jardin F. Combination of ofatumumab and reduced-dose CHOP for diffuse large B-cell lymphomas in patients aged 80 years or older: an open-label, multicentre, single-arm, phase 2 trial from the LYSA group. Lancet Haematol. 2017 Jan;4(1):e46-e55. [https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(16)30171-5/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28041583 PubMed]
 ==R-BL {{#subobject:fe578a|Regimen=1}}==
@@ Line 1,478: / Line 1,596: @@
 ===Regimen {{#subobject:f063a7|Variant=1}}===
 {| class="wikitable" style="width: 75%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 33%" |Study
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
+! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/bjh.14049/abstract Hitz et al. 2016 (SAKK 38/08)]
-|style="background-color:#91cf61"|Phase II, <20 pts in subgroup
+| style="background-color:#91cf61" |Phase II, <20 pts in subgroup
 |ORR: 61% (95% CI 45-76%)
 |-
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Bendamustine]] 70 mg/m<sup>2</sup> IV once per day on days 1 & 2
@@ Line 1,495: / Line 1,614: @@
 ===References===
-# Hitz F, Zucca E, Pabst T, Fischer N, Cairoli A, Samaras P, Caspar CB, Mach N, Krasniqi F, Schmidt A, Rothermundt C, Enoiu M, Eckhardt K, Berardi Vilei S, Rondeau S, Mey U. Rituximab, bendamustine and lenalidomide in patients with aggressive B-cell lymphoma not eligible for anthracycline-based therapy or intensive salvage chemotherapy - SAKK 38/08. Br J Haematol. 2016 Jul;174(2):255-63. Epub 2016 Mar 28. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.14049/abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27018242 PubMed]
+#Hitz F, Zucca E, Pabst T, Fischer N, Cairoli A, Samaras P, Caspar CB, Mach N, Krasniqi F, Schmidt A, Rothermundt C, Enoiu M, Eckhardt K, Berardi Vilei S, Rondeau S, Mey U. Rituximab, bendamustine and lenalidomide in patients with aggressive B-cell lymphoma not eligible for anthracycline-based therapy or intensive salvage chemotherapy - SAKK 38/08. Br J Haematol. 2016 Jul;174(2):255-63. Epub 2016 Mar 28. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.14049/abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27018242 PubMed]
 ==R-CDOP {{#subobject:bdf229|Regimen=1}}==
@@ Line 1,507: / Line 1,627: @@
 ===Regimen variant #1 {{#subobject:7a864b|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(14)00411-X/fulltext Oki et al. 2014 (MDACC 2004-0305)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Chemotherapy====
 *[[Pegylated liposomal doxorubicin (Doxil)]] 40 mg/m<sup>2</sup> (maximum dose of 90 mg) IV over 60 minutes once on day 1
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 1,522: / Line 1,643: @@
 ====Supportive medications====
 *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day from day 2 until ANC greater than 3000/μl
 OR
 *[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 2
 ====Dose modifications====
 *Dose reduction level 1 (see paper for triggers):
 **[[Pegylated liposomal doxorubicin (Doxil)]] reduced to 35 mg/m<sup>2</sup>
@@ Line 1,538: / Line 1,663: @@
 ===Regimen variant #2 {{#subobject:5fd9ca|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.tandfonline.com/doi/full/10.1080/10428190600799946 Zaja et al. 2006]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 1,548: / Line 1,673: @@
 ''Only the dose of liposomal doxorubicin and number of cycles used was specified in the abstract. The doses of the other medications and schedule are provided based on the standard R-CHOP regimen, whose references can be found on this page.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 1,557: / Line 1,683: @@
 ===References===
-# Zaja F, Tomadini V, Zaccaria A, Lenoci M, Battista M, Molinari AL, Fabbri A, Battista R, Cabras MG, Gallamini A, Fanin R. CHOP-rituximab with pegylated liposomal doxorubicin for the treatment of elderly patients with diffuse large B-cell lymphoma. Leuk Lymphoma. 2006 Oct;47(10):2174-80. [https://www.tandfonline.com/doi/full/10.1080/10428190600799946 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17071492 PubMed]
-# '''MDACC 2004-0305:''' Oki Y, Ewer MS, Lenihan DJ, Fisch MJ, Hagemeister FB, Fanale M, Romaguera J, Pro B, Fowler N, Younes A, Astrow AB, Huang X, Kwak LW, Samaniego F, McLaughlin P, Neelapu SS, Wang M, Fayad LE, Durand JB, Rodriguez MA. Pegylated liposomal doxorubicin replacing conventional doxorubicin in standard R-CHOP chemotherapy for elderly patients with diffuse large B-cell lymphoma: an open label, single arm, phase II trial. Clin Lymphoma Myeloma Leuk. 2015 Mar;15(3):152-8. Epub 2014 Sep 28. [http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(14)00411-X/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4344896/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25445468 PubMed]
+#Zaja F, Tomadini V, Zaccaria A, Lenoci M, Battista M, Molinari AL, Fabbri A, Battista R, Cabras MG, Gallamini A, Fanin R. CHOP-rituximab with pegylated liposomal doxorubicin for the treatment of elderly patients with diffuse large B-cell lymphoma. Leuk Lymphoma. 2006 Oct;47(10):2174-80. [https://www.tandfonline.com/doi/full/10.1080/10428190600799946 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17071492 PubMed]
+#'''MDACC 2004-0305:''' Oki Y, Ewer MS, Lenihan DJ, Fisch MJ, Hagemeister FB, Fanale M, Romaguera J, Pro B, Fowler N, Younes A, Astrow AB, Huang X, Kwak LW, Samaniego F, McLaughlin P, Neelapu SS, Wang M, Fayad LE, Durand JB, Rodriguez MA. Pegylated liposomal doxorubicin replacing conventional doxorubicin in standard R-CHOP chemotherapy for elderly patients with diffuse large B-cell lymphoma: an open label, single arm, phase II trial. Clin Lymphoma Myeloma Leuk. 2015 Mar;15(3):152-8. Epub 2014 Sep 28. [http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(14)00411-X/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4344896/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25445468 PubMed]
 ==R-CEOP90 (Epirubicin) {{#subobject:ebcd7e|Regimen=1}}==
@@ Line 1,569: / Line 1,696: @@
 ===Regimen variant #1, 4 cycles {{#subobject:d0b303|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.tandfonline.com/doi/full/10.3109/10428194.2013.876632 Cai et al. 2014]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''This regimen is intended to reduce cardiotoxicity and was not just for patients with contraindicated doxorubicin. Note that the cycle length is not explicitly defined in the paper but was reported as a median of 21 days (range 21 to 33 days).''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 2
@@ Line 1,586: / Line 1,714: @@
 '''21-day cycle for 4 cycles'''
 ====Subsequent treatment====
 *Patients with stage IA or IIA disease with bulky disease and extranodal and residual masses: [[#Radiation_therapy|IFRT]], 30 to 45 Gy
 ===Regimen variant #2, 6 cycles {{#subobject:d1cd34|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.tandfonline.com/doi/full/10.3109/10428194.2013.876632 Cai et al. 2014]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''This regimen is intended to reduce cardiotoxicity and was not just for patients with contraindicated doxorubicin. Note that the cycle length is not explicitly defined in the paper but was reported as a median of 21 days (range 21 to 33 days).''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 2
@@ Line 1,607: / Line 1,737: @@
 '''21-day cycle for 6 cycles''
 ===References===
-# Cai QC, Gao Y, Wang XX, Cai QQ, Lin ZX, Bai B, Guo Y, Huang HQ. Long-term results of the R-CEOP90 in the treatment of young patients with chemotherapy-naïve diffuse large B cell lymphoma: a phase II study. Leuk Lymphoma. 2014 Oct;55(10):2387-8. [https://www.tandfonline.com/doi/full/10.3109/10428194.2013.876632 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24528221 PubMed]
+#Cai QC, Gao Y, Wang XX, Cai QQ, Lin ZX, Bai B, Guo Y, Huang HQ. Long-term results of the R-CEOP90 in the treatment of young patients with chemotherapy-naïve diffuse large B cell lymphoma: a phase II study. Leuk Lymphoma. 2014 Oct;55(10):2387-8. [https://www.tandfonline.com/doi/full/10.3109/10428194.2013.876632 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24528221 PubMed]
 ==R-CEOP (Etoposide) {{#subobject:dfb13d|Regimen=1}}==
@@ Line 1,618: / Line 1,749: @@
 ===Regimen {{#subobject:d69b11|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://abstracts.hematologylibrary.org/cgi/content/abstract/114/22/408 Moccia et al. 2009]
-|style="background-color:#ffffbe"|Retrospective
+| style="background-color:#ffffbe" |Retrospective
 |-
 |}
@@ Line 1,628: / Line 1,759: @@
 ''This regimen is intended for patients with a contraindication to anthracyclines. Only the dose of etoposide and number of cycles used was specified in the abstract. The doses of the other medications and schedule are provided based on the standard R-CHOP regimen, whose references can be found on this page.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 1,638: / Line 1,770: @@
 ===References===
-# '''Retrospective:''' '''Abstract:''' Moccia, Alden A., Schaff, Kimberly, Hoskins, Paul, Klasa, Richard, Savage, Kerry J., Shenkier, Tamara, Gascoyne, Randy D., Connors, Joseph M., Sehn, Laurie H. R-CHOP with Etoposide Substituted for Doxorubicin (R-CEOP): Excellent Outcome in Diffuse Large B Cell Lymphoma for Patients with a Contraindication to Anthracyclines. ASH Annual Meeting Abstracts 2009 114: 408 [http://abstracts.hematologylibrary.org/cgi/content/abstract/114/22/408 link to abstract]
+#'''Retrospective:''' '''Abstract:''' Moccia, Alden A., Schaff, Kimberly, Hoskins, Paul, Klasa, Richard, Savage, Kerry J., Shenkier, Tamara, Gascoyne, Randy D., Connors, Joseph M., Sehn, Laurie H. R-CHOP with Etoposide Substituted for Doxorubicin (R-CEOP): Excellent Outcome in Diffuse Large B Cell Lymphoma for Patients with a Contraindication to Anthracyclines. ASH Annual Meeting Abstracts 2009 114: 408 [http://abstracts.hematologylibrary.org/cgi/content/abstract/114/22/408 link to abstract]
 ==R-CHMP {{#subobject:5510fa|Regimen=1}}==
@@ Line 1,648: / Line 1,781: @@
 ===Regimen variant #1, 3 cycles {{#subobject:e77893|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/bjh.12446/full Hagemeister et al. 2013]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''This regimen was intended for stage I patients with no LN greater than 5 cm.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 1,665: / Line 1,799: @@
 '''21-day cycle for 3 cycles'''
 ====Subsequent treatment====
 *[[#Radiation_therapy|RT]]
 ===Regimen variant #2, 6 cycles {{#subobject:a8501b|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/bjh.12446/full Hagemeister et al. 2013]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 1,686: / Line 1,822: @@
 ===References===
-# Hagemeister F, Rodriguez MA, Deitcher SR, Younes A, Fayad L, Goy A, Dang NH, Forman A, McLaughlin P, Medeiros LJ, Pro B, Romaguera J, Samaniego F, Silverman JA, Sarris A, Cabanillas F. Long term results of a phase 2 study of vincristine sulfate liposome injection (Marqibo(®) ) substituted for non-liposomal vincristine in cyclophosphamide, doxorubicin, vincristine, prednisone with or without rituximab for patients with untreated aggressive non-Hodgkin lymphomas. Br J Haematol. 2013 Sep;162(5):631-8. Epub 2013 Jun 27. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.12446/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23802738 PubMed]
+#Hagemeister F, Rodriguez MA, Deitcher SR, Younes A, Fayad L, Goy A, Dang NH, Forman A, McLaughlin P, Medeiros LJ, Pro B, Romaguera J, Samaniego F, Silverman JA, Sarris A, Cabanillas F. Long term results of a phase 2 study of vincristine sulfate liposome injection (Marqibo(®) ) substituted for non-liposomal vincristine in cyclophosphamide, doxorubicin, vincristine, prednisone with or without rituximab for patients with untreated aggressive non-Hodgkin lymphomas. Br J Haematol. 2013 Sep;162(5):631-8. Epub 2013 Jun 27. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.12446/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23802738 PubMed]
 ==R-GCVP {{#subobject:dff264|Regimen=1}}==
@@ Line 1,697: / Line 1,834: @@
 ===Regimen {{#subobject:dad22|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://jco.ascopubs.org/content/32/4/282.full Fields et al. 2013 (UCL/05/154)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 1,707: / Line 1,844: @@
 ''Intended for use in patients unlikely to tolerate anthracyclines due to cardiac comorbidity.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Gemcitabine (Gemzar)]] as follows:
 **Cycle 1: 750 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8
 **Cycle 2: 875 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8
 **Cycles 3 to 6: 1000 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8
@@ Line 1,717: / Line 1,855: @@
 ====Supportive medications====
 *[[Acetaminophen (Tylenol)]] 1000 mg (route not specified) once on day 1, prior to [[Rituximab (Rituxan)]]
 *[[Chlorpheniramine (Chlor-Trimeton)]] 10 mg IV once on day 1, prior to [[Rituximab (Rituxan)]]
@@ Line 1,722: / Line 1,861: @@
 ====CNS prophylaxis====
 *[[Methotrexate (MTX)]] 12.5 mg IT x 3 cycles (timing not specified) for patients at high risk of CNS relapse
@@ Line 1,728: / Line 1,868: @@
 ===References===
 <!-- Presented at the 53rd Annual Meeting of the American Society of Hematology, San Diego, CA, December 10-13, 2011. -->
-# '''UCL/05/154:''' Fields PA, Townsend W, Webb A, Counsell N, Pocock C, Smith P, Jack A, El-Mehidi N, Johnson PW, Radford J, Linch DC, Cunningham D. De novo treatment of diffuse large B-cell lymphoma with rituximab, cyclophosphamide, vincristine, gemcitabine, and prednisolone in patients with cardiac comorbidity: a United kingdom national cancer research institute trial. J Clin Oncol. 2014 Feb 1;32(4):282-7. Epub 2013 Nov 12. [http://jco.ascopubs.org/content/32/4/282.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24220559 PubMed]
+#'''UCL/05/154:''' Fields PA, Townsend W, Webb A, Counsell N, Pocock C, Smith P, Jack A, El-Mehidi N, Johnson PW, Radford J, Linch DC, Cunningham D. De novo treatment of diffuse large B-cell lymphoma with rituximab, cyclophosphamide, vincristine, gemcitabine, and prednisolone in patients with cardiac comorbidity: a United kingdom national cancer research institute trial. J Clin Oncol. 2014 Feb 1;32(4):282-7. Epub 2013 Nov 12. [http://jco.ascopubs.org/content/32/4/282.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24220559 PubMed]
 ==R-MegaCHOP {{#subobject:4e9b3e|Regimen=1}}==
@@ Line 1,739: / Line 1,880: @@
 ===Regimen {{#subobject:c3f62c|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/bjh.13036/full Pardal et al. 2014 (GELTAMO-2006)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 1500 mg/m<sup>2</sup> IV once on day 1
@@ Line 1,754: / Line 1,896: @@
 ====Supportive medications====
 *[[Pegfilgrastim (Neulasta)]] given after each cycle
 '''21-day cycle for 3 cycles'''
 ====Subsequent treatment====
 *Negative PET-CT after 3 cycles: another 3 cycles of R-MegaCHOP for a total of 6 cycles
 *Positive PET-CT after 3 cycles: [[#R-IFE_2|R-IFE]]
 ===References===
-# '''GELTAMO-2006:''' Pardal E, Coronado M, Martín A, Grande C, Marín-Niebla A, Panizo C, Bello JL, Conde E, Hernández MT, Arranz R, Bargay J, González-Barca E, Pérez-Ceballos E, Montes-Moreno S, Caballero MD. Intensification treatment based on early FDG-PET in patients with high-risk diffuse large B-cell lymphoma: a phase II GELTAMO trial. Br J Haematol. 2014 Nov;167(3):327-36. Epub 2014 Jul 28. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13036/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25066542 PubMed]
+#'''GELTAMO-2006:''' Pardal E, Coronado M, Martín A, Grande C, Marín-Niebla A, Panizo C, Bello JL, Conde E, Hernández MT, Arranz R, Bargay J, González-Barca E, Pérez-Ceballos E, Montes-Moreno S, Caballero MD. Intensification treatment based on early FDG-PET in patients with high-risk diffuse large B-cell lymphoma: a phase II GELTAMO trial. Br J Haematol. 2014 Nov;167(3):327-36. Epub 2014 Jul 28. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13036/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25066542 PubMed]
 ==R-miniCHOP {{#subobject:17bb83|Regimen=1}}==
@@ Line 1,773: / Line 1,918: @@
 ===Regimen {{#subobject:9fd3ee|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70069-9/fulltext Peyrade et al. 2011]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 400 mg/m<sup>2</sup> IV once on day 1
@@ Line 1,786: / Line 1,932: @@
 *[[Vincristine (Oncovin)]] 1 mg IV once on day 1
 *[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
 **No dose adjustments for hematologic toxicity. If needed, the subsequent R-miniCHOP cycle was postponed until ANC was greater than or equal to 1000/uL and platelet count was greater than or equal to 100 x 10<sup>9</sup>/L, with a maximum of 28 days between cycles. Treatment was stopped if patients' counts were not adequate within 28 days.
 ====Supportive medications====
 *"Prevention of tumour lysis syndrome by alkalinisation or hypouricaemic drugs was done if necessary."
 *[[:Category:Serotonin_5-HT3_antagonists | Serotonin (5-HT3) antagonist]] given every cycle.
@@ Line 1,797: / Line 1,944: @@
 ===References===
-# Peyrade F, Jardin F, Thieblemont C, Thyss A, Emile JF, Castaigne S, Coiffier B, Haioun C, Bologna S, Fitoussi O, Lepeu G, Fruchart C, Bordessoule D, Blanc M, Delarue R, Janvier M, Salles B, André M, Fournier M, Gaulard P, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte (GELA) investigators. Attenuated immunochemotherapy regimen (R-miniCHOP) in elderly patients older than 80 years with diffuse large B-cell lymphoma: a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2011 May;12(5):460-8. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70069-9/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21482186 PubMed]
+#Peyrade F, Jardin F, Thieblemont C, Thyss A, Emile JF, Castaigne S, Coiffier B, Haioun C, Bologna S, Fitoussi O, Lepeu G, Fruchart C, Bordessoule D, Blanc M, Delarue R, Janvier M, Salles B, André M, Fournier M, Gaulard P, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte (GELA) investigators. Attenuated immunochemotherapy regimen (R-miniCHOP) in elderly patients older than 80 years with diffuse large B-cell lymphoma: a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2011 May;12(5):460-8. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70069-9/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21482186 PubMed]
 ==R2CHOP {{#subobject:2a4e31|Regimen=1}}==
@@ Line 1,809: / Line 1,957: @@
 ===Regimen variant #1, len 15 mg/day for 14 d/cycle {{#subobject:6fc8a3|Variant=1}}===
 {| class="wikitable" style="width: 75%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 33%" |Study
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
+! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
 |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70191-3/fulltext Vitolo et al. 2014 (REAL07)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 | style="background-color:#f7fcfd" |ORR: 92% (95% CI 81–97)
 |-
@@ Line 1,820: / Line 1,968: @@
 ''Note: CNS prophylaxis was offered to "at risk" patients.''
 ====Chemotherapy====
 *[[Lenalidomide (Revlimid)]] 15 mg PO once per day on days 1 to 14
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 1,828: / Line 1,977: @@
 ====CNS prophylaxis====
 *[[Methotrexate (MTX)]] as follows:
 **Cycles 1 to 4: 12 mg IT once on day 1
 ====Supportive medications====
 *[[:Category:Granulocyte_colony-stimulating_factors|Granulocyte colony-stimulating factors]] (dose/duration not specified)
 *[[:Category:Low_molecular_weight_heparins|Low-molecular-weight heparins]] (dose/duration not specified)
@@ Line 1,843: / Line 1,994: @@
 ===Regimen variant #2, len 25 mg/day for 10 d/cycle {{#subobject:ea91fc|Variant=1}}===
 {| class="wikitable" style="width: 75%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 33%" |Study
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
+! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
 |[http://jco.ascopubs.org/content/33/3/251.full Nowakowski et al. 2014 (Mayo Clinic MC078E)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 | style="background-color:#f7fcfd" |ORR: 98%
 |-
 |}
 ====Chemotherapy====
 *[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 10
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 1,861: / Line 2,013: @@
 ====Supportive medications====
 *[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 2
 *[[Aspirin]] 81 mg PO once per day unless on therapeutic dose [[Warfarin (Coumadin)]] or [[:Category:Low_molecular_weight_heparins|low molecular weight heparin]]
@@ Line 1,870: / Line 2,023: @@
 # '''Phase 1:''' Chiappella A, Tucci A, Castellino A, Pavone V, Baldi I, Carella AM, Orsucci L, Zanni M, Salvi F, Liberati AM, Gaidano G, Bottelli C, Rossini B, Perticone S, De Masi P, Ladetto M, Ciccone G, Palumbo A, Rossi G, Vitolo U. Lenalidomide plus cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab is safe and effective in untreated elderly diffuse large B-cell lymphoma patients: phase I study by the Fondazione Italiana Linfomi. Haematologica. 2013 Nov;98(11):1732-8. Epub 2013 Jun 28. [http://www.haematologica.org/content/98/11/1732 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3815174/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23812930 PubMed] -->
 <!-- # '''Abstract:''' Chiappella A et al. Rituximab-CHOP21 plus lenalidomide (LR-CHOP21) is effective and feasible in elderly untreated diffuse large B-cell lymphoma (DLBCL): Results of Phase II REAL07 study of the Fondazione Italiana Linfomi (FIL). Proc ASH 2012; [http://abstracts.hematologylibrary.org/cgi/content/abstract/120/21/903?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=abstract+903&searchid=1&FIRSTINDEX=0&volume=120&issue=21&resourcetype=HWCIT Abstract 903]. -->
-# '''REAL07:''' Vitolo U, Chiappella A, Franceschetti S, Carella AM, Baldi I, Inghirami G, Spina M, Pavone V, Ladetto M, Liberati AM, Molinari AL, Zinzani P, Salvi F, Fattori PP, Zaccaria A, Dreyling M, Botto B, Castellino A, Congiu A, Gaudiano M, Zanni M, Ciccone G, Gaidano G, Rossi G; Fondazione Italiana Linfomi. Lenalidomide plus R-CHOP21 in elderly patients with untreated diffuse large B-cell lymphoma: results of the REAL07 open-label, multicentre, phase 2 trial. Lancet Oncol. 2014 Jun;15(7):730-7. Epub 2014 May 12. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70191-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24831981 PubMed]
+#'''REAL07:''' Vitolo U, Chiappella A, Franceschetti S, Carella AM, Baldi I, Inghirami G, Spina M, Pavone V, Ladetto M, Liberati AM, Molinari AL, Zinzani P, Salvi F, Fattori PP, Zaccaria A, Dreyling M, Botto B, Castellino A, Congiu A, Gaudiano M, Zanni M, Ciccone G, Gaidano G, Rossi G; Fondazione Italiana Linfomi. Lenalidomide plus R-CHOP21 in elderly patients with untreated diffuse large B-cell lymphoma: results of the REAL07 open-label, multicentre, phase 2 trial. Lancet Oncol. 2014 Jun;15(7):730-7. Epub 2014 May 12. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70191-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24831981 PubMed]
 <!--# '''Abstract:''' Nowakowski GS et al. Combination of lenalidomide with R-CHOP (R2CHOP) is well-tolerated and effective as initial therapy for aggressive B-cell lymphomas — A Phase II study. Proc ASH 2012; [http://abstracts.hematologylibrary.org/cgi/content/abstract/120/21/689?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=abstract+689&searchid=1&FIRSTINDEX=0&volume=120&issue=21&resourcetype=HWCIT Abstract 689].
 # '''Abstract:''' Grzegorz S. Nowakowski, Betsy LaPlant, William R Macon, Craig B. Reeder, James M. Foran, Garth D. Nelson, Carrie A. Thompson, Candido Rivera, David James Inwards, Ivana N. M. Micallef, Patrick B. Johnston, Luis F. Porrata, Stephen Maxted Ansell, Thomas Matthew Habermann, Thomas E. Witzig. Effect of lenalidomide combined with R-CHOP (R2CHOP) on negative prognostic impact of nongerminal center (non-GCB) phenotype in newly diagnosed diffuse large B-cell lymphoma: A phase 2 study. J Clin Oncol 32:5s, 2014 (suppl; abstr 8520) [http://meetinglibrary.asco.org/content/134031-144 link to original abstract] -->
-# '''Mayo Clinic MC078E:''' Nowakowski GS, LaPlant B, Macon WR, Reeder CB, Foran JM, Nelson GD, Thompson CA, Rivera CE, Inwards DJ, Micallef IN, Johnston PB, Porrata LF, Ansell SM, Gascoyne RD, Habermann TM, Witzig TE. Lenalidomide combined with R-CHOP overcomes negative prognostic impact of non-germinal center B-cell phenotype in newly diagnosed diffuse large B-cell lymphoma: a phase II study. J Clin Oncol. 2015 Jan 20;33(3):251-7. Epub 2014 Aug 18. [http://jco.ascopubs.org/content/33/3/251.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25135992 PubMed]
+#'''Mayo Clinic MC078E:''' Nowakowski GS, LaPlant B, Macon WR, Reeder CB, Foran JM, Nelson GD, Thompson CA, Rivera CE, Inwards DJ, Micallef IN, Johnston PB, Porrata LF, Ansell SM, Gascoyne RD, Habermann TM, Witzig TE. Lenalidomide combined with R-CHOP overcomes negative prognostic impact of non-germinal center B-cell phenotype in newly diagnosed diffuse large B-cell lymphoma: a phase II study. J Clin Oncol. 2015 Jan 20;33(3):251-7. Epub 2014 Aug 18. [http://jco.ascopubs.org/content/33/3/251.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25135992 PubMed]
 =Consolidation after upfront therapy=
@@ Line 1,884: / Line 2,038: @@
 ===Regimen {{#subobject:00b635|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985418/ Stiff et al. 2013 (SWOG S9704)]
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#1a9851" |Phase III (E-esc)
 |[[#R-CHOP|R-CHOP x 8]]
-|style="background-color:#1a9850"|Superior PFS
+| style="background-color:#1a9850" |Superior PFS
 |-
 |}
 ====Preceding treatment====
 *[[#R-CHOP|R-CHOP]] x 6
 {{#lst:Autologous HSCT conditioning regimens|6fc278}}
 ===References===
-# '''SWOG S9704:''' Stiff PJ, Unger JM, Cook JR, Constine LS, Couban S, Stewart DA, Shea TC, Porcu P, Winter JN, Kahl BS, Miller TP, Tubbs RR, Marcellus D, Friedberg JW, Barton KP, Mills GM, LeBlanc M, Rimsza LM, Forman SJ, Fisher RI. Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. N Engl J Med. 2013 Oct 31;369(18):1681-90. [https://www.nejm.org/doi/full/10.1056/NEJMoa1301077 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985418/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24171516 PubMed]
-## '''Subgroup analysis:''' Puvvada SD, Stiff PJ, Leblanc M, Cook JR, Couban S, Leonard JP, Kahl B, Marcellus D, Shea TC, Winter JN, Li H, Rimsza LM, Friedberg JW, Smith SM. Outcomes of MYC-associated lymphomas after R-CHOP with and without consolidative autologous stem cell transplant: subset analysis of randomized trial intergroup SWOG S9704. Br J Haematol. 2016 Sep;174(5):686-91. Epub 2016 Apr 13. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.14100/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125530/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27072903 PubMed]
+#'''SWOG S9704:''' Stiff PJ, Unger JM, Cook JR, Constine LS, Couban S, Stewart DA, Shea TC, Porcu P, Winter JN, Kahl BS, Miller TP, Tubbs RR, Marcellus D, Friedberg JW, Barton KP, Mills GM, LeBlanc M, Rimsza LM, Forman SJ, Fisher RI. Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. N Engl J Med. 2013 Oct 31;369(18):1681-90. [https://www.nejm.org/doi/full/10.1056/NEJMoa1301077 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985418/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24171516 PubMed]
+##'''Subgroup analysis:''' Puvvada SD, Stiff PJ, Leblanc M, Cook JR, Couban S, Leonard JP, Kahl B, Marcellus D, Shea TC, Winter JN, Li H, Rimsza LM, Friedberg JW, Smith SM. Outcomes of MYC-associated lymphomas after R-CHOP with and without consolidative autologous stem cell transplant: subset analysis of randomized trial intergroup SWOG S9704. Br J Haematol. 2016 Sep;174(5):686-91. Epub 2016 Apr 13. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.14100/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125530/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27072903 PubMed]
 ==CBVM, then auto HSCT {{#subobject:59bb2c|Regimen=1}}==
@@ Line 1,909: / Line 2,065: @@
 ===Regimen {{#subobject:bbedec|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://annonc.oxfordjournals.org/content/20/12/1985.long Haioun et al. 2009 (LNH 98-3)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |}
 ====Preceding treatment====
 *[[Diffuse_large_B-cell_lymphoma_-_historical#ACE|ACE]] versus [[Diffuse_large_B-cell_lymphoma_-_historical#ACVBP|ACVBP]]
 ====Chemotherapy====
 *[[Carmustine (BCNU)]]
 *[[Etoposide (Vepesid)]]
@@ Line 1,926: / Line 2,085: @@
 '''Stem cells reinfused afterwards (unclear which day)'''
 ====Subsequent treatment====
 *[[#Observation|Observation]] versus [[#Rituximab_monotherapy|rituximab maintenance]]
 ===References===
-# '''LNH 98-3:''' Haioun C, Mounier N, Emile JF, Ranta D, Coiffier B, Tilly H, Récher C, Fermé C, Gabarre J, Herbrecht R, Morchhauser F, Gisselbrecht C. Rituximab versus observation after high-dose consolidative first-line chemotherapy with autologous stem-cell transplantation in patients with poor-risk diffuse large B-cell lymphoma. Ann Oncol. 2009 Dec;20(12):1985-92. Epub 2009 Jun 30. [http://annonc.oxfordjournals.org/content/20/12/1985.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19567453 PubMed]
+#'''LNH 98-3:''' Haioun C, Mounier N, Emile JF, Ranta D, Coiffier B, Tilly H, Récher C, Fermé C, Gabarre J, Herbrecht R, Morchhauser F, Gisselbrecht C. Rituximab versus observation after high-dose consolidative first-line chemotherapy with autologous stem-cell transplantation in patients with poor-risk diffuse large B-cell lymphoma. Ann Oncol. 2009 Dec;20(12):1985-92. Epub 2009 Jun 30. [http://annonc.oxfordjournals.org/content/20/12/1985.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19567453 PubMed]
 ==Cytarabine monotherapy {{#subobject:fa5ce3|Regimen=1}}==
@@ Line 1,939: / Line 2,100: @@
 ===Regimen {{#subobject:4f9fa6|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61040-4/fulltext Récher et al. 2011 (LNH03-2B)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |[http://annonc.oxfordjournals.org/content/24/4/1032.long Ketterer et al. 2013 (LNH03-1B)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |}
 ====Preceding treatment====
 *[[#R-IFE|REI consolidation]] x 4
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> SC once per day on days 1 to 4
@@ Line 1,957: / Line 2,121: @@
 ===References===
-# '''LNH03-2B:''' Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, Thiéblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquières H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011 Nov 26;378(9806):1858-67. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61040-4/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22118442 PubMed]
-## '''Subgroup analysis:''' Molina TJ, Canioni D, Copie-Bergman C, Recher C, Brière J, Haioun C, Berger F, Fermé C, Copin MC, Casasnovas O, Thieblemont C, Petrella T, Leroy K, Salles G, Fabiani B, Morschauser F, Mounier N, Coiffier B, Jardin F, Gaulard P, Jais JP, Tilly H. Young patients with non-germinal center B-cell-like diffuse large B-cell lymphoma benefit from intensified chemotherapy with ACVBP plus rituximab compared with CHOP plus rituximab: analysis of data from the Groupe d'Etudes des Lymphomes de l'Adulte/lymphoma study association phase III trial LNH 03-2B. J Clin Oncol. 2014 Dec 10;32(35):3996-4003. Epub 2014 Nov 10. [https://ascopubs.org/doi/full/10.1200/JCO.2013.54.9493 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25385729 PubMed]
+#'''LNH03-2B:''' Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, Thiéblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquières H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011 Nov 26;378(9806):1858-67. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61040-4/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22118442 PubMed]
-# '''LNH03-1B:''' Ketterer N, Coiffier B, Thieblemont C, Fermé C, Brière J, Casasnovas O, Bologna S, Christian B, Connerotte T, Récher C, Bordessoule D, Fruchart C, Delarue R, Bonnet C, Morschhauser F, Anglaret B, Soussain C, Fabiani B, Tilly H, Haioun C. Phase III study of ACVBP versus ACVBP plus rituximab for patients with localized low-risk diffuse large B-cell lymphoma (LNH03-1B). Ann Oncol. 2013 Apr;24(4):1032-7. Epub 2012 Dec 12. [http://annonc.oxfordjournals.org/content/24/4/1032.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23235801 PubMed]
+##'''Subgroup analysis:''' Molina TJ, Canioni D, Copie-Bergman C, Recher C, Brière J, Haioun C, Berger F, Fermé C, Copin MC, Casasnovas O, Thieblemont C, Petrella T, Leroy K, Salles G, Fabiani B, Morschauser F, Mounier N, Coiffier B, Jardin F, Gaulard P, Jais JP, Tilly H. Young patients with non-germinal center B-cell-like diffuse large B-cell lymphoma benefit from intensified chemotherapy with ACVBP plus rituximab compared with CHOP plus rituximab: analysis of data from the Groupe d'Etudes des Lymphomes de l'Adulte/lymphoma study association phase III trial LNH 03-2B. J Clin Oncol. 2014 Dec 10;32(35):3996-4003. Epub 2014 Nov 10. [https://ascopubs.org/doi/full/10.1200/JCO.2013.54.9493 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25385729 PubMed]
+#'''LNH03-1B:''' Ketterer N, Coiffier B, Thieblemont C, Fermé C, Brière J, Casasnovas O, Bologna S, Christian B, Connerotte T, Récher C, Bordessoule D, Fruchart C, Delarue R, Bonnet C, Morschhauser F, Anglaret B, Soussain C, Fabiani B, Tilly H, Haioun C. Phase III study of ACVBP versus ACVBP plus rituximab for patients with localized low-risk diffuse large B-cell lymphoma (LNH03-1B). Ann Oncol. 2013 Apr;24(4):1032-7. Epub 2012 Dec 12. [http://annonc.oxfordjournals.org/content/24/4/1032.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23235801 PubMed]
 ==Ibritumomab tiuxetan monotherapy {{#subobject:85625d|Regimen=1}}==
@@ Line 1,968: / Line 2,133: @@
 ===Regimen variant #1, no cap {{#subobject:a989fb|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691189/ Witzig et al. 2015 (ECOG E3402)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Preceding treatment====
 *[[#R-CHOP|R-CHOP]] x 4 to 6
 ====Radioimmunotherapy====
 *[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once per day on days 1 & 8
-*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin) ]] 14.8 MBq/kg IV once on day 8
+*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]] 14.8 MBq/kg IV once on day 8
 '''8-day course'''
 ====Subsequent treatment====
 *Patients with CT or PET positive disease 12 weeks after radioimmunotherapy: [[#Radiation_therapy|30 Gy of IFRT]]
 ===Regimen variant #2, capped dose {{#subobject:dfc019|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287635/ Persky et al. 2014 (SWOG S0313)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Preceding treatment====
 *[[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]] x 3, then [[#Radiation_therapy|IFRT]]
 ====Radioimmunotherapy====
 *[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once per day on days 1 & 8 +/- 1 day, '''given first on day 7, 8, or 9'''
-*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin) ]] 0.4 mCi/kg (maximum dose of 32 mCi) IV once on day 8 +/- 1 day, '''given second, within 4 hours of rituximab'''
+*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]] 0.4 mCi/kg (maximum dose of 32 mCi) IV once on day 8 +/- 1 day, '''given second, within 4 hours of rituximab'''
 ===References===
-# '''SWOG S0313:''' Persky DO, Miller TP, Unger JM, Spier CM, Puvvada S, Stea BD, Press OW, Constine LS, Barton KP, Friedberg JW, LeBlanc M, Fisher RI. Ibritumomab consolidation after 3 cycles of CHOP plus radiotherapy in high-risk limited-stage aggressive B-cell lymphoma: SWOG S0313. Blood. 2015 Jan 8;125(2):236-41. Epub 2014 Nov 13. [http://www.bloodjournal.org/content/125/2/236.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287635/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25395425 PubMed]
-# '''ECOG E3402:''' Witzig TE, Hong F, Micallef IN, Gascoyne RD, Dogan A, Wagner H Jr, Kahl BS, Advani RH, Horning SJ. A phase II trial of RCHOP followed by radioimmunotherapy for early stage (stages I/II) diffuse large B-cell non-Hodgkin lymphoma: ECOG3402. Br J Haematol. 2015 Sep;170(5):679-86. Epub 2015 May 14. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13493/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691189/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25974212 PubMed]
+#'''SWOG S0313:''' Persky DO, Miller TP, Unger JM, Spier CM, Puvvada S, Stea BD, Press OW, Constine LS, Barton KP, Friedberg JW, LeBlanc M, Fisher RI. Ibritumomab consolidation after 3 cycles of CHOP plus radiotherapy in high-risk limited-stage aggressive B-cell lymphoma: SWOG S0313. Blood. 2015 Jan 8;125(2):236-41. Epub 2014 Nov 13. [http://www.bloodjournal.org/content/125/2/236.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287635/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25395425 PubMed]
+#'''ECOG E3402:''' Witzig TE, Hong F, Micallef IN, Gascoyne RD, Dogan A, Wagner H Jr, Kahl BS, Advani RH, Horning SJ. A phase II trial of RCHOP followed by radioimmunotherapy for early stage (stages I/II) diffuse large B-cell non-Hodgkin lymphoma: ECOG3402. Br J Haematol. 2015 Sep;170(5):679-86. Epub 2015 May 14. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13493/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691189/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25974212 PubMed]
 ==Methotrexate monotherapy {{#subobject:d77e3a|Regimen=1}}==
@@ Line 2,012: / Line 2,185: @@
 ===Regimen {{#subobject:b1d075|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61040-4/fulltext Récher et al. 2011 (LNH03-2B)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |[http://annonc.oxfordjournals.org/content/24/4/1032.long Ketterer et al. 2013 (LNH03-1B)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |}
 ====Preceding treatment====
 *[[#ACVBP-R|ACVBP-R induction]] x 4
 ====Chemotherapy====
 *[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV once on day 1
 ====Supportive medications====
 *[[Folinic acid (Leucovorin)|Calcium folinate - Folinic acid (Leucovorin)]] rescue
 '''14-day cycle for 2 cycles'''
 ====Subsequent treatment====
 *[[#R-IFE|REI consolidation]], in 2 weeks
 ===References===
-# '''LNH03-2B:''' Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, Thiéblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquières H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011 Nov 26;378(9806):1858-67. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61040-4/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22118442 PubMed]
-## '''Subgroup analysis:''' Molina TJ, Canioni D, Copie-Bergman C, Recher C, Brière J, Haioun C, Berger F, Fermé C, Copin MC, Casasnovas O, Thieblemont C, Petrella T, Leroy K, Salles G, Fabiani B, Morschauser F, Mounier N, Coiffier B, Jardin F, Gaulard P, Jais JP, Tilly H. Young patients with non-germinal center B-cell-like diffuse large B-cell lymphoma benefit from intensified chemotherapy with ACVBP plus rituximab compared with CHOP plus rituximab: analysis of data from the Groupe d'Etudes des Lymphomes de l'Adulte/lymphoma study association phase III trial LNH 03-2B. J Clin Oncol. 2014 Dec 10;32(35):3996-4003. Epub 2014 Nov 10. [https://ascopubs.org/doi/full/10.1200/JCO.2013.54.9493 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25385729 PubMed]
+#'''LNH03-2B:''' Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, Thiéblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquières H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011 Nov 26;378(9806):1858-67. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61040-4/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22118442 PubMed]
-# '''LNH03-1B:''' Ketterer N, Coiffier B, Thieblemont C, Fermé C, Brière J, Casasnovas O, Bologna S, Christian B, Connerotte T, Récher C, Bordessoule D, Fruchart C, Delarue R, Bonnet C, Morschhauser F, Anglaret B, Soussain C, Fabiani B, Tilly H, Haioun C. Phase III study of ACVBP versus ACVBP plus rituximab for patients with localized low-risk diffuse large B-cell lymphoma (LNH03-1B). Ann Oncol. 2013 Apr;24(4):1032-7. Epub 2012 Dec 12. [http://annonc.oxfordjournals.org/content/24/4/1032.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23235801 PubMed]
+##'''Subgroup analysis:''' Molina TJ, Canioni D, Copie-Bergman C, Recher C, Brière J, Haioun C, Berger F, Fermé C, Copin MC, Casasnovas O, Thieblemont C, Petrella T, Leroy K, Salles G, Fabiani B, Morschauser F, Mounier N, Coiffier B, Jardin F, Gaulard P, Jais JP, Tilly H. Young patients with non-germinal center B-cell-like diffuse large B-cell lymphoma benefit from intensified chemotherapy with ACVBP plus rituximab compared with CHOP plus rituximab: analysis of data from the Groupe d'Etudes des Lymphomes de l'Adulte/lymphoma study association phase III trial LNH 03-2B. J Clin Oncol. 2014 Dec 10;32(35):3996-4003. Epub 2014 Nov 10. [https://ascopubs.org/doi/full/10.1200/JCO.2013.54.9493 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25385729 PubMed]
+#'''LNH03-1B:''' Ketterer N, Coiffier B, Thieblemont C, Fermé C, Brière J, Casasnovas O, Bologna S, Christian B, Connerotte T, Récher C, Bordessoule D, Fruchart C, Delarue R, Bonnet C, Morschhauser F, Anglaret B, Soussain C, Fabiani B, Tilly H, Haioun C. Phase III study of ACVBP versus ACVBP plus rituximab for patients with localized low-risk diffuse large B-cell lymphoma (LNH03-1B). Ann Oncol. 2013 Apr;24(4):1032-7. Epub 2012 Dec 12. [http://annonc.oxfordjournals.org/content/24/4/1032.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23235801 PubMed]
 ==Observation==
@@ Line 2,046: / Line 2,225: @@
 ===Regimen===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://jco.ascopubs.org/content/22/15/3032.long Horning et al. 2004 (ECOG E1484)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#Radiation_therapy|IFRT]]
-|style="background-color:#fc8d59"|Seems to have inferior DFS
+| style="background-color:#fc8d59" |Seems to have inferior DFS
 |-
 |[http://jco.ascopubs.org/content/24/19/3121.long Habermann et al. 2006 (ECOG E4494/CALGB 9793)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#Rituximab_monotherapy|Rituximab]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of FFS
 |-
 |[https://ascopubs.org/doi/full/10.1200/JCO.2006.07.0722 Bonnet et al. 2007]
-|style="background-color:#1a9851"|Phase III (E-de-esc)
+| style="background-color:#1a9851" |Phase III (E-de-esc)
 |[[#Radiation_therapy|IFRT]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 |-
 |[http://annonc.oxfordjournals.org/content/20/12/1985.long Haioun et al. 2009 (LNH 98-3)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#Rituximab_monotherapy|Rituximab]]
-|style="background-color:#fee08b"|Might have inferior EFS
+| style="background-color:#fee08b" |Might have inferior EFS
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4486230/ Jaeger et al. 2015 (NHL13)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#Rituximab_monotherapy|Rituximab]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of EFS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/bjh.13652/full Witzens-Harig et al. 2015 (HD2002)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#Rituximab_monotherapy|Rituximab]]
-|style="background-color:#d73027"|Inferior OS in males
+| style="background-color:#d73027" |Inferior OS in males
 |-
 |[http://www.bloodjournal.org/content/131/2/174.long Lamy et al. 2017 (LYSA/GOELAMS 02-03)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#Radiation_therapy|IFRT]]
-|style="background-color:#eeee00"|Non-inferior EFS
+| style="background-color:#eeee00" |Non-inferior EFS
 |-
 |}
 ''No further treatment, also variously termed "observation" and "watchful waiting". Note: in ECOG E4494/CALGB 9793, a statistically signficant disadvantage to observation was seen in the group receiving [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP induction]], which is no longer standard of care.''
 ====Preceding treatment====
 *ECOG E1484: [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]] x 8, with CR
 *ECOG E4494/CALGB 9793: [[#R-CHOP|R-CHOP]] versus [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]] induction
 *Bonnet et al. 2007: [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]] x 4
 *LNH 98-3: [[#CBVM.2C_then_auto_HSCT|CBVM, then auto HSCT consolidation]]
 *HD2002: "Standard treatment"
 *LYSA/GOELAMS 02-03: [[#R-CHOP-14|R-CHOP-14]] x 4 to 6
 ===References===
-# '''ECOG E1484:''' Horning SJ, Weller E, Kim K, Earle JD, O'Connell MJ, Habermann TM, Glick JH. Chemotherapy with or without radiotherapy in limited-stage diffuse aggressive non-Hodgkin's lymphoma: Eastern Cooperative Oncology Group study 1484. J Clin Oncol. 2004 Aug 1;22(15):3032-8. Epub 2004 Jun 21. [http://jco.ascopubs.org/content/22/15/3032.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15210738 PubMed]
-# '''ECOG E4494/CALGB 9793:''' Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, Dakhil SR, Woda B, Fisher RI, Peterson BA, Horning SJ. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006 Jul 1;24(19):3121-7. Epub 2006 Jun 5. [http://jco.ascopubs.org/content/24/19/3121.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16754935 PubMed]
+#'''ECOG E1484:''' Horning SJ, Weller E, Kim K, Earle JD, O'Connell MJ, Habermann TM, Glick JH. Chemotherapy with or without radiotherapy in limited-stage diffuse aggressive non-Hodgkin's lymphoma: Eastern Cooperative Oncology Group study 1484. J Clin Oncol. 2004 Aug 1;22(15):3032-8. Epub 2004 Jun 21. [http://jco.ascopubs.org/content/22/15/3032.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15210738 PubMed]
-# Bonnet C, Fillet G, Mounier N, Ganem G, Molina TJ, Thiéblemont C, Fermé C, Quesnel B, Martin C, Gisselbrecht C, Tilly H, Reyes F; Groupe d'Etude des Lymphomes de l'Adulte. CHOP alone compared with CHOP plus radiotherapy for localized aggressive lymphoma in elderly patients: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2007 Mar 1;25(7):787-92. Epub 2007 Jan 16. [https://ascopubs.org/doi/full/10.1200/JCO.2006.07.0722 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17228021 PubMed]
+#'''ECOG E4494/CALGB 9793:''' Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, Dakhil SR, Woda B, Fisher RI, Peterson BA, Horning SJ. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006 Jul 1;24(19):3121-7. Epub 2006 Jun 5. [http://jco.ascopubs.org/content/24/19/3121.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16754935 PubMed]
-# '''LNH 98-3:''' Haioun C, Mounier N, Emile JF, Ranta D, Coiffier B, Tilly H, Récher C, Fermé C, Gabarre J, Herbrecht R, Morchhauser F, Gisselbrecht C. Rituximab versus observation after high-dose consolidative first-line chemotherapy with autologous stem-cell transplantation in patients with poor-risk diffuse large B-cell lymphoma. Ann Oncol. 2009 Dec;20(12):1985-92. Epub 2009 Jun 30. [http://annonc.oxfordjournals.org/content/20/12/1985.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19567453 PubMed]
+#Bonnet C, Fillet G, Mounier N, Ganem G, Molina TJ, Thiéblemont C, Fermé C, Quesnel B, Martin C, Gisselbrecht C, Tilly H, Reyes F; Groupe d'Etude des Lymphomes de l'Adulte. CHOP alone compared with CHOP plus radiotherapy for localized aggressive lymphoma in elderly patients: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2007 Mar 1;25(7):787-92. Epub 2007 Jan 16. [https://ascopubs.org/doi/full/10.1200/JCO.2006.07.0722 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17228021 PubMed]
+#'''LNH 98-3:''' Haioun C, Mounier N, Emile JF, Ranta D, Coiffier B, Tilly H, Récher C, Fermé C, Gabarre J, Herbrecht R, Morchhauser F, Gisselbrecht C. Rituximab versus observation after high-dose consolidative first-line chemotherapy with autologous stem-cell transplantation in patients with poor-risk diffuse large B-cell lymphoma. Ann Oncol. 2009 Dec;20(12):1985-92. Epub 2009 Jun 30. [http://annonc.oxfordjournals.org/content/20/12/1985.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19567453 PubMed]
 <!-- These data have been presented in part at the 55th Annual Meeting of the American Society of Hematology, New Orleans 2013, the 12th International Conference on Malignant Lymphoma 2013, Lugano, and the 18th Congress of the European Hematology Association, Stockholm 2013. -->
-# '''NHL13:''' Jaeger U, Trneny M, Melzer H, Praxmarer M, Nawarawong W, Ben Yehuda D, Goldstein D, Mihaljevic B, Ilhan O, Ballova V, Hedenus M, Hsiao LT, Au WY, Burgstaller S, Weidinger G, Keil F, Dittrich C, Skrabs C, Klingler A, Chott A, Fridrik MA, Greil R. Rituximab maintenance for patients with aggressive B-cell lymphoma in first remission: results of the randomized NHL13 trial. Haematologica. 2015 Jul;100(7):955-63. Epub 2015 Apr 24. [http://www.haematologica.org/content/100/7/955 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4486230/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25911553 PubMed]
+#'''NHL13:''' Jaeger U, Trneny M, Melzer H, Praxmarer M, Nawarawong W, Ben Yehuda D, Goldstein D, Mihaljevic B, Ilhan O, Ballova V, Hedenus M, Hsiao LT, Au WY, Burgstaller S, Weidinger G, Keil F, Dittrich C, Skrabs C, Klingler A, Chott A, Fridrik MA, Greil R. Rituximab maintenance for patients with aggressive B-cell lymphoma in first remission: results of the randomized NHL13 trial. Haematologica. 2015 Jul;100(7):955-63. Epub 2015 Apr 24. [http://www.haematologica.org/content/100/7/955 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4486230/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25911553 PubMed]
-# '''HD2002:''' Witzens-Harig M, Benner A, McClanahan F, Klemmer J, Brandt J, Brants E, Rieger M, Meissner J, Hensel M, Neben K, Dreger P, Lengfelder E, Schmidt-Wolf I, Krämer A, Ho AD. Rituximab maintenance improves survival in male patients with diffuse large B-cell lymphoma: results of the HD2002 prospective multicentre randomized phase III trial. Br J Haematol. 2015 Dec;171(5):710-9. Epub 2015 Oct 9. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13652/full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26449739 PubMed]
+#'''HD2002:''' Witzens-Harig M, Benner A, McClanahan F, Klemmer J, Brandt J, Brants E, Rieger M, Meissner J, Hensel M, Neben K, Dreger P, Lengfelder E, Schmidt-Wolf I, Krämer A, Ho AD. Rituximab maintenance improves survival in male patients with diffuse large B-cell lymphoma: results of the HD2002 prospective multicentre randomized phase III trial. Br J Haematol. 2015 Dec;171(5):710-9. Epub 2015 Oct 9. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13652/full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26449739 PubMed]
-# '''LYSA/GOELAMS 02-03:''' Lamy T, Damaj G, Soubeyran P, Gyan E, Cartron G, Bouabdallah K, Gressin R, Cornillon J, Banos A, Le Du K, Benchalal M, Moles MP, Le Gouill S, Fleury J, Godmer P, Maisonneuve H, Deconinck E, Houot R, Laribi K, Marolleau JP, Tournilhac O, Branger B, Devillers A, Vuillez JP, Fest T, Colombat P, Costes V, Szablewski V, Béné MC, Delwail V; LYSA Group. R-CHOP 14 with or without radiotherapy in nonbulky limited-stage diffuse large B-cell lymphoma. Blood. 2018 Jan 11;131(2):174-181. Epub 2017 Oct 23. [http://www.bloodjournal.org/content/131/2/174.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29061568 PubMed]
+#'''LYSA/GOELAMS 02-03:''' Lamy T, Damaj G, Soubeyran P, Gyan E, Cartron G, Bouabdallah K, Gressin R, Cornillon J, Banos A, Le Du K, Benchalal M, Moles MP, Le Gouill S, Fleury J, Godmer P, Maisonneuve H, Deconinck E, Houot R, Laribi K, Marolleau JP, Tournilhac O, Branger B, Devillers A, Vuillez JP, Fest T, Colombat P, Costes V, Szablewski V, Béné MC, Delwail V; LYSA Group. R-CHOP 14 with or without radiotherapy in nonbulky limited-stage diffuse large B-cell lymphoma. Blood. 2018 Jan 11;131(2):174-181. Epub 2017 Oct 23. [http://www.bloodjournal.org/content/131/2/174.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29061568 PubMed]
 ==Placebo==
@@ Line 2,113: / Line 2,294: @@
 ===Regimen===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://jco.ascopubs.org/content/34/21/2484.full Crump et al. 2016 (PRELUDE)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |Enzastaurin
-|style="background-color:#ffffbf"|Did not meet primary endpoint of DFS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 |-
 |[https://ascopubs.org/doi/full/10.1200/JCO.2017.72.6984 Thieblemont et al. 2017 (REMARC)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#Lenalidomide_monotherapy|Lenalidomide]]
-|style="background-color:#fc8d59"|Seems to have inferior PFS
+| style="background-color:#fc8d59" |Seems to have inferior PFS
 |-
 |[https://academic.oup.com/annonc/article-abstract/29/3/707/4748817 Witzig et al. 2018 (PILLAR-2)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |Everolimus
-|style="background-color:#ffffbf"|Did not meet primary endpoint of DFS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 |-
 |}
 ''No further antineoplastic treatment.''
 ====Preceding treatment====
-*PRELUDE: [[#R-CHOP|R-CHOP induction]]
+*PRELUDE: [[#R-CHOP|R-CHOP induction]]
 *REMARC: [[#R-CHOP|R-CHOP21]] or [[#R-CHOP-14|R-CHOP-14]] induction
 ===References===
 <!-- Presented in part at the Annual Meeting of the American Society of Hematology, New Orleans, LA, December 8, 2013, and at the Annual Meeting of the American Association for Cancer Research, Philadelphia, PA, April 22, 2015. -->
-# '''PRELUDE:''' Crump M, Leppä S, Fayad L, Lee JJ, Di Rocco A, Ogura M, Hagberg H, Schnell F, Rifkin R, Mackensen A, Offner F, Pinter-Brown L, Smith S, Tobinai K, Yeh SP, Hsi ED, Nguyen T, Shi P, Hahka-Kemppinen M, Thornton D, Lin B, Kahl B, Schmitz N, Savage KJ, Habermann T. Randomized, double-blind, phase III trial of enzastaurin versus placebo in patients achieving remission after first-line therapy for high-risk diffuse large B-cell lymphoma. J Clin Oncol. 2016 Jul 20;34(21):2484-92. Epub 2016 May 23. [http://jco.ascopubs.org/content/34/21/2484.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27217449 PubMed]
+#'''PRELUDE:''' Crump M, Leppä S, Fayad L, Lee JJ, Di Rocco A, Ogura M, Hagberg H, Schnell F, Rifkin R, Mackensen A, Offner F, Pinter-Brown L, Smith S, Tobinai K, Yeh SP, Hsi ED, Nguyen T, Shi P, Hahka-Kemppinen M, Thornton D, Lin B, Kahl B, Schmitz N, Savage KJ, Habermann T. Randomized, double-blind, phase III trial of enzastaurin versus placebo in patients achieving remission after first-line therapy for high-risk diffuse large B-cell lymphoma. J Clin Oncol. 2016 Jul 20;34(21):2484-92. Epub 2016 May 23. [http://jco.ascopubs.org/content/34/21/2484.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27217449 PubMed]
 <!-- # '''Abstract:''' Catherine Thieblemont, Hervé Tilly, Maria Gomez da Silva, Rene-Olivier Casasnovas, Christophe Fruchart, Franck Morschhauser, Corinne Haioun, Julien Lazarovici, Sebastian Grosicki, Aurore Perrot, Judith Trotman, Catherine Sebban, Dolores Caballero, Richard Greil, Koen Van Eygen, Josette Briere, Jose Cabecadas, Gilles Andre Salles, Philippe Gaulard, Andre Bosly and Bertrand Coiffier. First Analysis of an International Double-Blind Randomized Phase III Study of Lenalidomide Maintenance in Elderly Patients with DLBCL Treated with R-CHOP in First Line, the Remarc Study from Lysa. Blood 2016 128:471 [http://www.bloodjournal.org/content/128/22/471 link to abstract] -->
-# '''REMARC:''' Thieblemont C, Tilly H, Gomes da Silva M, Casasnovas RO, Fruchart C, Morschhauser F, Haioun C, Lazarovici J, Grosicka A, Perrot A, Trotman J, Sebban C, Caballero D, Greil R, van Eygen K, Cohen AM, Gonzalez H, Bouabdallah R, Oberic L, Corront B, Choufi B, Lopez-Guillermo A, Catalano J, Van Hoof A, Briere J, Cabeçadas J, Salles G, Gaulard P, Bosly A, Coiffier B. Lenalidomide maintenance compared with placebo in responding elderly patients with diffuse large B-cell lymphoma treated with first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol. 2017 Aug 1;35(22):2473-2481. Epub 2017 Apr 20. [https://ascopubs.org/doi/full/10.1200/JCO.2017.72.6984 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28426350 PubMed]
+#'''REMARC:''' Thieblemont C, Tilly H, Gomes da Silva M, Casasnovas RO, Fruchart C, Morschhauser F, Haioun C, Lazarovici J, Grosicka A, Perrot A, Trotman J, Sebban C, Caballero D, Greil R, van Eygen K, Cohen AM, Gonzalez H, Bouabdallah R, Oberic L, Corront B, Choufi B, Lopez-Guillermo A, Catalano J, Van Hoof A, Briere J, Cabeçadas J, Salles G, Gaulard P, Bosly A, Coiffier B. Lenalidomide maintenance compared with placebo in responding elderly patients with diffuse large B-cell lymphoma treated with first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol. 2017 Aug 1;35(22):2473-2481. Epub 2017 Apr 20. [https://ascopubs.org/doi/full/10.1200/JCO.2017.72.6984 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28426350 PubMed]
 <!-- # '''Abstract:''' Thomas E. Witzig, Kensei Tobinai, Luigi Rigacci, Tongyu Lin, Takashi Ikeda, Anna Vanazzi, Masayuki Hino, Yuankai Shi, Jiri Mayer, Luciano J Costa, Carlos Daniel Bermudez, Jun Zhu, David Belada, Kamal Bouabdallah, Joseph Gergi Kattan, Cassandra Wu, Jenna Fan, Anne-Laure Louveau, Maurizio Voi, and Franco Cavalli. PILLAR-2: A randomized, double-blind, placebo-controlled, phase III study of adjuvant everolimus (EVE) in patients (pts) with poor-risk diffuse large B-cell lymphoma (DLBCL). Journal of Clinical Oncology 2016 34:15_suppl, 7506-7506 [https://ascopubs.org/doi/full/10.1200/JCO.2016.34.15_suppl.7506 link to abstract] -->
-# '''PILLAR-2:''' Witzig TE, Tobinai K, Rigacci L, Ikeda T, Vanazzi A, Hino M, Shi Y, Mayer J, Costa LJ, Bermudez Silva CD, Zhu J, Belada D, Bouabdallah K, Kattan JG, Kuruvilla J, Kim WS, Larouche JF, Ogura M, Ozcan M, Fayad L, Wu C, Fan J, Louveau AL, Voi M, Cavalli F. Adjuvant everolimus in high-risk diffuse large B-cell lymphoma: final results from the PILLAR-2 randomized phase III trial. Ann Oncol. 2018 Mar 1;29(3):707-714. [https://academic.oup.com/annonc/article-abstract/29/3/707/4748817 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29253068 PubMed]
+#'''PILLAR-2:''' Witzig TE, Tobinai K, Rigacci L, Ikeda T, Vanazzi A, Hino M, Shi Y, Mayer J, Costa LJ, Bermudez Silva CD, Zhu J, Belada D, Bouabdallah K, Kattan JG, Kuruvilla J, Kim WS, Larouche JF, Ogura M, Ozcan M, Fayad L, Wu C, Fan J, Louveau AL, Voi M, Cavalli F. Adjuvant everolimus in high-risk diffuse large B-cell lymphoma: final results from the PILLAR-2 randomized phase III trial. Ann Oncol. 2018 Mar 1;29(3):707-714. [https://academic.oup.com/annonc/article-abstract/29/3/707/4748817 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29253068 PubMed]
 ==Radiation therapy {{#subobject:98e441|Regimen=1}}==
@@ Line 2,153: / Line 2,337: @@
 ===Regimen variant #1, testicular irradiation {{#subobject:a72fd1|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://jco.ascopubs.org/content/29/20/2766.long Vitolo et al. 2011 (IELSG-10)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Preceding treatment====
 *[[#R-CHOP|R-CHOP]] x 6 to 8 cycles
 ====Radiotherapy====
 *[[External beam radiotherapy]] 25 to 30 Gy to the contralateral testis. For patients with stage II disease, involved-field radiation therapy was added; see paper for details.
 ===Regimen variant #2, IFRT x 30 Gy {{#subobject:54f3d9|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://jco.ascopubs.org/content/22/15/3032.long Horning et al. 2004 (ECOG E1484)]
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#1a9851" |Phase III (E-esc)
 |[[#Observation|Observation]]
 | style="background-color:#91cf60" |Seems to have superior DFS
@@ Line 2,179: / Line 2,366: @@
 |}
 ====Preceding treatment====
 *ECOG E1484: [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]] x 8, with CR
 ====Radiotherapy====
 *[[External beam radiotherapy|IFRT]] 30 Gy
 ===Regimen variant #3, 36 Gy {{#subobject:214e87|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://www.bloodjournal.org/content/104/3/634.long Pfreundschuh et al. 2004 (NHL-B2)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2808%2970002-0/fulltext Pfreundschuh et al. 2008 (RICOVER-60)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70481-3/fulltext Schmitz et al. 2012 (DSHNHL 2002-1)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |[http://jco.ascopubs.org/content/32/36/4127.full Pfreundschuh et al. 2014 (SMARTE-R-CHOP-14)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Preceding treatment====
 *NHL-B2: [[Diffuse_large_B-cell_lymphoma_-_historical#CHOEP-14|CHOEP-14]] x 6 versus [[Diffuse_large_B-cell_lymphoma_-_historical#CHOEP-21|CHOEP-21]] x 6 versus [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP-14|CHOP-14]] x 6 versus [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP-21]] x 6
 *RICOVER-60: [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP-14|CHOP-14]] x 6 versus [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP-14|CHOP-14]] x 8 versus [[#R-CHOP-14|R-CHOP-14]] x 6 versus [[#R-CHOP-14|R-CHOP-14]] x 8
 *DSHNHL 2002-1: [[#R-CHOEP-14|R-CHOEP-14]] x 8 versus R-MegaCHOEP
 *SMARTE-R-CHOP-14: [[#R-CHOP-14|R-CHOP-14]] x 6
 ====Radiotherapy====
 *[[External beam radiotherapy]] 36 Gy in daily fractions
 ===Regimen variant #4, IFRT x 40 Gy {{#subobject:54f3d9|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://jco.ascopubs.org/content/22/15/3032.long Horning et al. 2004 (ECOG E1484)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[https://ascopubs.org/doi/full/10.1200/JCO.2006.07.0722 Bonnet et al. 2007]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#Observation|Observation]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287635/ Persky et al. 2014 (SWOG S0313)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[http://www.bloodjournal.org/content/131/2/174.long Lamy et al. 2017 (LYSA/GOELAMS 02-03)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#Observation|Observation]]
-|style="background-color:#eeee00"|Non-inferior EFS
+| style="background-color:#eeee00" |Non-inferior EFS
 |-
 |}
 ====Preceding treatment====
 *ECOG E1484: [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]] x 8, with PR
 *SWOG S0313: [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]] x 3, with CR
 *Bonnet et al. 2007: [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]] x 4
 *LYSA/GOELAMS 02-03: [[#R-CHOP-14|R-CHOP-14]] x 4 to 6
 ====Radiotherapy====
 *[[External beam radiotherapy]] 40 Gy in daily fractions of 1.80 to 2.00 Gy
 ====Subsequent treatment====
 *SWOG S0313: [[#Ibritumomab_tiuxetan_monotherapy|Ibritumomab tiuxetan consolidation]]
 ===Regimen variant #5, IFRT x 40 to 55 Gy {{#subobject:0cd919|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.nejm.org/doi/full/10.1056/NEJM199807023390104 Miller et al. 1998 (SWOG S8736)]
-|style="background-color:#1a9851"|Phase III (E-switch-ooc)
+| style="background-color:#1a9851" |Phase III (E-switch-ooc)
 |[[Complex_multipart_regimens#SWOG_S8736|See link]]
 |[[Complex_multipart_regimens#SWOG_S8736|See link]]
 |-
 |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2806%2970664-7/fulltext Pfreundschuh et al. 2006 (NCIC CTG LY.9)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[http://jco.ascopubs.org/content/26/14/2258.long Persky et al. 2008 (SWOG S0014)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287635/ Persky et al. 2014 (SWOG S0313)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |}
 ''Note: these studies did not specify an exact dose; see papers for details.''
 ====Preceding treatment====
 *SWOG S8736 and SWOG S0014: [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]] x 3
 *NCIC CTG LY.9: CHOP-like therapy x 6 versus R-CHOP-like therapy x 6
 *SWOG S0313: [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]] x 3, with PR
 ====Radiotherapy====
 *[[External beam radiotherapy]] 46 to 50 Gy in daily fractions of 1.80 to 2.00 Gy
 ====Subsequent treatment====
 *SWOG S0313: [[#Ibritumomab_tiuxetan_monotherapy|Ibritumumoab tiuxetan consolidation]]
 ===References===
-# '''SWOG S8736:''' Miller TP, Dahlberg S, Cassady JR, Adelstein DJ, Spier CM, Grogan TM, LeBlanc M, Carlin S, Chase E, Fisher RI. Chemotherapy alone compared with chemotherapy plus radiotherapy for localized intermediate- and high-grade non-Hodgkin's lymphoma. N Engl J Med. 1998 Jul 2;339(1):21-6. [https://www.nejm.org/doi/full/10.1056/NEJM199807023390104 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9647875 PubMed]
-## '''Update:''' Stephens DM, Li H, LeBlanc ML, Puvvada SD, Persky D, Friedberg JW, Smith SM. Continued risk of relapse independent of treatment modality in limited-stage diffuse large B-cell lymphoma: Final and long-term analysis of Southwest Oncology Group study S8736. J Clin Oncol. 2016 Sep 1;34(25):2997-3004. Epub 2016 Jul 5. [http://jco.ascopubs.org/content/34/25/2997.full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5012710/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27382104 PubMed]
+#'''SWOG S8736:''' Miller TP, Dahlberg S, Cassady JR, Adelstein DJ, Spier CM, Grogan TM, LeBlanc M, Carlin S, Chase E, Fisher RI. Chemotherapy alone compared with chemotherapy plus radiotherapy for localized intermediate- and high-grade non-Hodgkin's lymphoma. N Engl J Med. 1998 Jul 2;339(1):21-6. [https://www.nejm.org/doi/full/10.1056/NEJM199807023390104 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9647875 PubMed]
-# '''NHL-B2:''' Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rübe C, Rudolph C, Reiser M, Hossfeld DK, Eimermacher H, Hasenclever D, Schmitz N, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):634-41. Epub 2004 Mar 11. [http://www.bloodjournal.org/content/104/3/634.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15016643 PubMed]
+##'''Update:''' Stephens DM, Li H, LeBlanc ML, Puvvada SD, Persky D, Friedberg JW, Smith SM. Continued risk of relapse independent of treatment modality in limited-stage diffuse large B-cell lymphoma: Final and long-term analysis of Southwest Oncology Group study S8736. J Clin Oncol. 2016 Sep 1;34(25):2997-3004. Epub 2016 Jul 5. [http://jco.ascopubs.org/content/34/25/2997.full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5012710/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27382104 PubMed]
-# '''ECOG E1484:''' Horning SJ, Weller E, Kim K, Earle JD, O'Connell MJ, Habermann TM, Glick JH. Chemotherapy with or without radiotherapy in limited-stage diffuse aggressive non-Hodgkin's lymphoma: Eastern Cooperative Oncology Group study 1484. J Clin Oncol. 2004 Aug 1;22(15):3032-8. Epub 2004 Jun 21. [http://jco.ascopubs.org/content/22/15/3032.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15210738 PubMed]
+#'''NHL-B2:''' Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rübe C, Rudolph C, Reiser M, Hossfeld DK, Eimermacher H, Hasenclever D, Schmitz N, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):634-41. Epub 2004 Mar 11. [http://www.bloodjournal.org/content/104/3/634.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15016643 PubMed]
-# '''LNH 93-01:''' Reyes F, Lepage E, Ganem G, Molina TJ, Brice P, Coiffier B, Morel P, Ferme C, Bosly A, Lederlin P, Laurent G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte (GELA). ACVBP versus CHOP plus radiotherapy for localized aggressive lymphoma. N Engl J Med. 2005 Mar 24;352(12):1197-205. [https://www.nejm.org/doi/full/10.1056/NEJMoa042040 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15788496 PubMed]
+#'''ECOG E1484:''' Horning SJ, Weller E, Kim K, Earle JD, O'Connell MJ, Habermann TM, Glick JH. Chemotherapy with or without radiotherapy in limited-stage diffuse aggressive non-Hodgkin's lymphoma: Eastern Cooperative Oncology Group study 1484. J Clin Oncol. 2004 Aug 1;22(15):3032-8. Epub 2004 Jun 21. [http://jco.ascopubs.org/content/22/15/3032.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15210738 PubMed]
-# '''NCIC CTG LY.9:''' Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2806%2970664-7/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16648042 PubMed]
+#'''LNH 93-01:''' Reyes F, Lepage E, Ganem G, Molina TJ, Brice P, Coiffier B, Morel P, Ferme C, Bosly A, Lederlin P, Laurent G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte (GELA). ACVBP versus CHOP plus radiotherapy for localized aggressive lymphoma. N Engl J Med. 2005 Mar 24;352(12):1197-205. [https://www.nejm.org/doi/full/10.1056/NEJMoa042040 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15788496 PubMed]
-## '''Update:''' Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N; MabThera International Trial (MInT) Group. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011 Oct;12(11):1013-22. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2811%2970235-2/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21940214 PubMed]
+#'''NCIC CTG LY.9:''' Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2806%2970664-7/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16648042 PubMed]
-# Bonnet C, Fillet G, Mounier N, Ganem G, Molina TJ, Thiéblemont C, Fermé C, Quesnel B, Martin C, Gisselbrecht C, Tilly H, Reyes F; Groupe d'Etude des Lymphomes de l'Adulte. CHOP alone compared with CHOP plus radiotherapy for localized aggressive lymphoma in elderly patients: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2007 Mar 1;25(7):787-92. Epub 2007 Jan 16. [https://ascopubs.org/doi/full/10.1200/JCO.2006.07.0722 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17228021 PubMed]
+##'''Update:''' Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N; MabThera International Trial (MInT) Group. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011 Oct;12(11):1013-22. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2811%2970235-2/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21940214 PubMed]
-# '''RICOVER-60:''' Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, Reiser M, Nickenig C, Clemens M, Peter N, Bokemeyer C, Eimermacher H, Ho A, Hoffmann M, Mertelsmann R, Trümper L, Balleisen L, Liersch R, Metzner B, Hartmann F, Glass B, Poeschel V, Schmitz N, Ruebe C, Feller AC, Loeffler M; German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 2008 Feb;9(2):105-16. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2808%2970002-0/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18226581 PubMed]
+#Bonnet C, Fillet G, Mounier N, Ganem G, Molina TJ, Thiéblemont C, Fermé C, Quesnel B, Martin C, Gisselbrecht C, Tilly H, Reyes F; Groupe d'Etude des Lymphomes de l'Adulte. CHOP alone compared with CHOP plus radiotherapy for localized aggressive lymphoma in elderly patients: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2007 Mar 1;25(7):787-92. Epub 2007 Jan 16. [https://ascopubs.org/doi/full/10.1200/JCO.2006.07.0722 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17228021 PubMed]
-# '''SWOG S0014:''' Persky DO, Unger JM, Spier CM, Stea B, LeBlanc M, McCarty MJ, Rimsza LM, Fisher RI, Miller TP; Southwest Oncology Group. Phase II study of rituximab plus three cycles of CHOP and involved-field radiotherapy for patients with limited-stage aggressive B-cell lymphoma: Southwest Oncology Group study 0014. J Clin Oncol. 2008 May 10;26(14):2258-63. Epub 2008 Apr 14. [http://jco.ascopubs.org/content/26/14/2258.long link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18413640 PubMed]
+#'''RICOVER-60:''' Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, Reiser M, Nickenig C, Clemens M, Peter N, Bokemeyer C, Eimermacher H, Ho A, Hoffmann M, Mertelsmann R, Trümper L, Balleisen L, Liersch R, Metzner B, Hartmann F, Glass B, Poeschel V, Schmitz N, Ruebe C, Feller AC, Loeffler M; German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 2008 Feb;9(2):105-16. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2808%2970002-0/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18226581 PubMed]
-# '''IELSG-10:''' Vitolo U, Chiappella A, Ferreri AJ, Martelli M, Baldi I, Balzarotti M, Bottelli C, Conconi A, Gomez H, Lopez-Guillermo A, Martinelli G, Merli F, Novero D, Orsucci L, Pavone V, Ricardi U, Storti S, Gospodarowicz MK, Cavalli F, Sarris AH, Zucca E. First-line treatment for primary testicular diffuse large B-cell lymphoma with rituximab-CHOP, CNS prophylaxis, and contralateral testis irradiation: final results of an international phase II trial. J Clin Oncol. 2011 Jul 10;29(20):2766-72. Epub 2011 Jun 6. [http://jco.ascopubs.org/content/29/20/2766.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21646602 PubMed]
+#'''SWOG S0014:''' Persky DO, Unger JM, Spier CM, Stea B, LeBlanc M, McCarty MJ, Rimsza LM, Fisher RI, Miller TP; Southwest Oncology Group. Phase II study of rituximab plus three cycles of CHOP and involved-field radiotherapy for patients with limited-stage aggressive B-cell lymphoma: Southwest Oncology Group study 0014. J Clin Oncol. 2008 May 10;26(14):2258-63. Epub 2008 Apr 14. [http://jco.ascopubs.org/content/26/14/2258.long link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18413640 PubMed]
-# '''DSHNHL 2002-1:''' Schmitz N, Nickelsen M, Ziepert M, Haenel M, Borchmann P, Schmidt C, Viardot A, Bentz M, Peter N, Ehninger G, Doelken G, Ruebe C, Truemper L, Rosenwald A, Pfreundschuh M, Loeffler M, Glass B; for the German High-Grade Lymphoma Study Group (DSHNHL). Conventional chemotherapy (CHOEP-14) with rituximab or high-dose chemotherapy (MegaCHOEP) with rituximab for young, high-risk patients with aggressive B-cell lymphoma: an open-label, randomised, phase 3 trial (DSHNHL 2002-1). Lancet Oncol. 2012 Dec;13(12):1250-1259. Epub 2012 Nov 16. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70481-3/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23168367 PubMed]
+#'''IELSG-10:''' Vitolo U, Chiappella A, Ferreri AJ, Martelli M, Baldi I, Balzarotti M, Bottelli C, Conconi A, Gomez H, Lopez-Guillermo A, Martinelli G, Merli F, Novero D, Orsucci L, Pavone V, Ricardi U, Storti S, Gospodarowicz MK, Cavalli F, Sarris AH, Zucca E. First-line treatment for primary testicular diffuse large B-cell lymphoma with rituximab-CHOP, CNS prophylaxis, and contralateral testis irradiation: final results of an international phase II trial. J Clin Oncol. 2011 Jul 10;29(20):2766-72. Epub 2011 Jun 6. [http://jco.ascopubs.org/content/29/20/2766.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21646602 PubMed]
-# '''SWOG S0313:''' Persky DO, Miller TP, Unger JM, Spier CM, Puvvada S, Stea BD, Press OW, Constine LS, Barton KP, Friedberg JW, LeBlanc M, Fisher RI. Ibritumomab consolidation after 3 cycles of CHOP plus radiotherapy in high-risk limited-stage aggressive B-cell lymphoma: SWOG S0313. Blood. 2015 Jan 8;125(2):236-41. Epub 2014 Nov 13. [http://www.bloodjournal.org/content/125/2/236.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287635/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25395425 PubMed]
+#'''DSHNHL 2002-1:''' Schmitz N, Nickelsen M, Ziepert M, Haenel M, Borchmann P, Schmidt C, Viardot A, Bentz M, Peter N, Ehninger G, Doelken G, Ruebe C, Truemper L, Rosenwald A, Pfreundschuh M, Loeffler M, Glass B; for the German High-Grade Lymphoma Study Group (DSHNHL). Conventional chemotherapy (CHOEP-14) with rituximab or high-dose chemotherapy (MegaCHOEP) with rituximab for young, high-risk patients with aggressive B-cell lymphoma: an open-label, randomised, phase 3 trial (DSHNHL 2002-1). Lancet Oncol. 2012 Dec;13(12):1250-1259. Epub 2012 Nov 16. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70481-3/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23168367 PubMed]
-# '''SMARTE-R-CHOP-14:''' Pfreundschuh M, Poeschel V, Zeynalova S, Hänel M, Held G, Schmitz N, Viardot A, Dreyling MH, Hallek M, Mueller C, Wiesen MH, Witzens-Harig M, Truemper L, Keller U, Rixecker T, Zwick C, Murawski N. Optimization of rituximab for the treatment of diffuse large B-cell lymphoma (II): extended rituximab exposure time in the SMARTE-R-CHOP-14 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group. J Clin Oncol. 2014 Dec 20;32(36):4127-33. Epub 2014 Nov 17. Erratum in: J Clin Oncol. 2015 Jun 10;33(17):1991. [http://jco.ascopubs.org/content/32/36/4127.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25403207 PubMed]
+#'''SWOG S0313:''' Persky DO, Miller TP, Unger JM, Spier CM, Puvvada S, Stea BD, Press OW, Constine LS, Barton KP, Friedberg JW, LeBlanc M, Fisher RI. Ibritumomab consolidation after 3 cycles of CHOP plus radiotherapy in high-risk limited-stage aggressive B-cell lymphoma: SWOG S0313. Blood. 2015 Jan 8;125(2):236-41. Epub 2014 Nov 13. [http://www.bloodjournal.org/content/125/2/236.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287635/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25395425 PubMed]
-# '''LYSA/GOELAMS 02-03:''' Lamy T, Damaj G, Soubeyran P, Gyan E, Cartron G, Bouabdallah K, Gressin R, Cornillon J, Banos A, Le Du K, Benchalal M, Moles MP, Le Gouill S, Fleury J, Godmer P, Maisonneuve H, Deconinck E, Houot R, Laribi K, Marolleau JP, Tournilhac O, Branger B, Devillers A, Vuillez JP, Fest T, Colombat P, Costes V, Szablewski V, Béné MC, Delwail V; LYSA Group. R-CHOP 14 with or without radiotherapy in nonbulky limited-stage diffuse large B-cell lymphoma. Blood. 2018 Jan 11;131(2):174-181. Epub 2017 Oct 23. [http://www.bloodjournal.org/content/131/2/174.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29061568 PubMed]
+#'''SMARTE-R-CHOP-14:''' Pfreundschuh M, Poeschel V, Zeynalova S, Hänel M, Held G, Schmitz N, Viardot A, Dreyling MH, Hallek M, Mueller C, Wiesen MH, Witzens-Harig M, Truemper L, Keller U, Rixecker T, Zwick C, Murawski N. Optimization of rituximab for the treatment of diffuse large B-cell lymphoma (II): extended rituximab exposure time in the SMARTE-R-CHOP-14 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group. J Clin Oncol. 2014 Dec 20;32(36):4127-33. Epub 2014 Nov 17. Erratum in: J Clin Oncol. 2015 Jun 10;33(17):1991. [http://jco.ascopubs.org/content/32/36/4127.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25403207 PubMed]
+#'''LYSA/GOELAMS 02-03:''' Lamy T, Damaj G, Soubeyran P, Gyan E, Cartron G, Bouabdallah K, Gressin R, Cornillon J, Banos A, Le Du K, Benchalal M, Moles MP, Le Gouill S, Fleury J, Godmer P, Maisonneuve H, Deconinck E, Houot R, Laribi K, Marolleau JP, Tournilhac O, Branger B, Devillers A, Vuillez JP, Fest T, Colombat P, Costes V, Szablewski V, Béné MC, Delwail V; LYSA Group. R-CHOP 14 with or without radiotherapy in nonbulky limited-stage diffuse large B-cell lymphoma. Blood. 2018 Jan 11;131(2):174-181. Epub 2017 Oct 23. [http://www.bloodjournal.org/content/131/2/174.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29061568 PubMed]
 ==R-IFE {{#subobject:62de3a|Regimen=1}}==
@@ Line 2,311: / Line 2,515: @@
 ===Regimen {{#subobject:6de486|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61040-4/fulltext Récher et al. 2011 (LNH03-2B)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |[http://annonc.oxfordjournals.org/content/24/4/1032.long Ketterer et al. 2013 (LNH03-1B)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |}
 ====Preceding treatment====
 *[[#Methotrexate_monotherapy|Methotrexate consolidation]] x 2
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Etoposide (Vepesid)]] 300 mg/m<sup>2</sup> IV once on day 1
@@ Line 2,330: / Line 2,537: @@
 '''14-day cycle for 4 cycles'''
 ====Subsequent treatment====
 *[[#Cytarabine_monotherapy|Cytarabine consolidation]], in 2 weeks
 ===References===
-# '''LNH03-2B:''' Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, Thiéblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquières H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011 Nov 26;378(9806):1858-67. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61040-4/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22118442 PubMed]
-## '''Subgroup analysis:''' Molina TJ, Canioni D, Copie-Bergman C, Recher C, Brière J, Haioun C, Berger F, Fermé C, Copin MC, Casasnovas O, Thieblemont C, Petrella T, Leroy K, Salles G, Fabiani B, Morschauser F, Mounier N, Coiffier B, Jardin F, Gaulard P, Jais JP, Tilly H. Young patients with non-germinal center B-cell-like diffuse large B-cell lymphoma benefit from intensified chemotherapy with ACVBP plus rituximab compared with CHOP plus rituximab: analysis of data from the Groupe d'Etudes des Lymphomes de l'Adulte/lymphoma study association phase III trial LNH 03-2B. J Clin Oncol. 2014 Dec 10;32(35):3996-4003. Epub 2014 Nov 10. [https://ascopubs.org/doi/full/10.1200/JCO.2013.54.9493 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25385729 PubMed]
+#'''LNH03-2B:''' Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, Thiéblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquières H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011 Nov 26;378(9806):1858-67. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61040-4/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22118442 PubMed]
-# '''LNH03-1B:''' Ketterer N, Coiffier B, Thieblemont C, Fermé C, Brière J, Casasnovas O, Bologna S, Christian B, Connerotte T, Récher C, Bordessoule D, Fruchart C, Delarue R, Bonnet C, Morschhauser F, Anglaret B, Soussain C, Fabiani B, Tilly H, Haioun C. Phase III study of ACVBP versus ACVBP plus rituximab for patients with localized low-risk diffuse large B-cell lymphoma (LNH03-1B). Ann Oncol. 2013 Apr;24(4):1032-7. Epub 2012 Dec 12. [http://annonc.oxfordjournals.org/content/24/4/1032.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23235801 PubMed]
+##'''Subgroup analysis:''' Molina TJ, Canioni D, Copie-Bergman C, Recher C, Brière J, Haioun C, Berger F, Fermé C, Copin MC, Casasnovas O, Thieblemont C, Petrella T, Leroy K, Salles G, Fabiani B, Morschauser F, Mounier N, Coiffier B, Jardin F, Gaulard P, Jais JP, Tilly H. Young patients with non-germinal center B-cell-like diffuse large B-cell lymphoma benefit from intensified chemotherapy with ACVBP plus rituximab compared with CHOP plus rituximab: analysis of data from the Groupe d'Etudes des Lymphomes de l'Adulte/lymphoma study association phase III trial LNH 03-2B. J Clin Oncol. 2014 Dec 10;32(35):3996-4003. Epub 2014 Nov 10. [https://ascopubs.org/doi/full/10.1200/JCO.2013.54.9493 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25385729 PubMed]
+#'''LNH03-1B:''' Ketterer N, Coiffier B, Thieblemont C, Fermé C, Brière J, Casasnovas O, Bologna S, Christian B, Connerotte T, Récher C, Bordessoule D, Fruchart C, Delarue R, Bonnet C, Morschhauser F, Anglaret B, Soussain C, Fabiani B, Tilly H, Haioun C. Phase III study of ACVBP versus ACVBP plus rituximab for patients with localized low-risk diffuse large B-cell lymphoma (LNH03-1B). Ann Oncol. 2013 Apr;24(4):1032-7. Epub 2012 Dec 12. [http://annonc.oxfordjournals.org/content/24/4/1032.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23235801 PubMed]
 ==TBI, then auto HSCT {{#subobject:37bf17|Regimen=1}}==
@@ Line 2,344: / Line 2,553: @@
 ===Regimen {{#subobject:619e49|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985418/ Stiff et al. 2013 (SWOG S9704)]
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#1a9851" |Phase III (E-esc)
 |[[#R-CHOP|R-CHOP x 8]]
-|style="background-color:#1a9850"|Superior PFS
+| style="background-color:#1a9850" |Superior PFS
 |-
 |}
 ====Preceding treatment====
 *[[#R-CHOP|R-CHOP]] x 6
 {{#lst:Autologous HSCT conditioning regimens|635694}}
@@ Line 2,361: / Line 2,571: @@
 ===References===
-# '''SWOG S9704:''' Stiff PJ, Unger JM, Cook JR, Constine LS, Couban S, Stewart DA, Shea TC, Porcu P, Winter JN, Kahl BS, Miller TP, Tubbs RR, Marcellus D, Friedberg JW, Barton KP, Mills GM, LeBlanc M, Rimsza LM, Forman SJ, Fisher RI. Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. N Engl J Med. 2013 Oct 31;369(18):1681-90. [https://www.nejm.org/doi/full/10.1056/NEJMoa1301077 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985418/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24171516 PubMed]
-## '''Subgroup analysis:''' Puvvada SD, Stiff PJ, Leblanc M, Cook JR, Couban S, Leonard JP, Kahl B, Marcellus D, Shea TC, Winter JN, Li H, Rimsza LM, Friedberg JW, Smith SM. Outcomes of MYC-associated lymphomas after R-CHOP with and without consolidative autologous stem cell transplant: subset analysis of randomized trial intergroup SWOG S9704. Br J Haematol. 2016 Sep;174(5):686-91. Epub 2016 Apr 13. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.14100/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125530/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27072903 PubMed]
+#'''SWOG S9704:''' Stiff PJ, Unger JM, Cook JR, Constine LS, Couban S, Stewart DA, Shea TC, Porcu P, Winter JN, Kahl BS, Miller TP, Tubbs RR, Marcellus D, Friedberg JW, Barton KP, Mills GM, LeBlanc M, Rimsza LM, Forman SJ, Fisher RI. Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. N Engl J Med. 2013 Oct 31;369(18):1681-90. [https://www.nejm.org/doi/full/10.1056/NEJMoa1301077 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985418/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24171516 PubMed]
+##'''Subgroup analysis:''' Puvvada SD, Stiff PJ, Leblanc M, Cook JR, Couban S, Leonard JP, Kahl B, Marcellus D, Shea TC, Winter JN, Li H, Rimsza LM, Friedberg JW, Smith SM. Outcomes of MYC-associated lymphomas after R-CHOP with and without consolidative autologous stem cell transplant: subset analysis of randomized trial intergroup SWOG S9704. Br J Haematol. 2016 Sep;174(5):686-91. Epub 2016 Apr 13. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.14100/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125530/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27072903 PubMed]
 ==Z-BEAM, then auto HSCT {{#subobject:19f0d0|Regimen=1}}==
@@ Line 2,372: / Line 2,583: @@
 ===Regimen variant #1 {{#subobject:9aeafe|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1002/cncr.27418/full Shimoni et al. 2012 (SHEBA-07-4466-AN-CTIL)]
@@ Line 2,391: / Line 2,602: @@
 ===Regimen variant #2 {{#subobject:e7f161|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://www.bbmt.org/article/S1083-8791(14)00473-X/fulltext Fruchart et al. 2014 (ZBEAM2)]
@@ Line 2,399: / Line 2,610: @@
 |}
 ====Preceding treatment====
 *[[#ACVBP-R|R-ACVBP]] or [[#R-CHOP|R-CHOP]]
 {{#lst:Autologous HSCT|e7f161}}
 ===References===
-# Shimoni A, Zwas ST, Oksman Y, Hardan I, Shem-Tov N, Yerushalmi R, Avigdor A, Ben-Bassat I, Nagler A. Yttrium-90-ibritumomab tiuxetan (Zevalin) combined with high-dose BEAM chemotherapy and autologous stem cell transplantation for chemo-refractory aggressive non-Hodgkin's lymphoma. Exp Hematol. 2007 Apr;35(4):534-40. [http://www.exphem.org/article/S0301-472X(07)00050-1/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17379063 PubMed]
-# '''SHEBA-07-4466-AN-CTIL:''' Shimoni A, Avivi I, Rowe JM, Yeshurun M, Levi I, Or R, Patachenko P, Avigdor A, Zwas T, Nagler A. A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma. Cancer. 2012 Oct 1;118(19):4706-14. Epub 2012 Jan 17. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.27418/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22252613 PubMed]
+#Shimoni A, Zwas ST, Oksman Y, Hardan I, Shem-Tov N, Yerushalmi R, Avigdor A, Ben-Bassat I, Nagler A. Yttrium-90-ibritumomab tiuxetan (Zevalin) combined with high-dose BEAM chemotherapy and autologous stem cell transplantation for chemo-refractory aggressive non-Hodgkin's lymphoma. Exp Hematol. 2007 Apr;35(4):534-40. [http://www.exphem.org/article/S0301-472X(07)00050-1/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17379063 PubMed]
-# '''GELTAMO Z-BEAM LDCGB:''' Briones J, Novelli S, García-Marco JA, Tomás JF, Bernal T, Grande C, Canales MA, Torres A, Moraleda JM, Panizo C, Jarque I, Palmero F, Hernández M, González-Barca E, López D, Caballero D. Autologous stem cell transplantation after conditioning with Yttrium-90 ibritumomab tiuxetan plus beam in refractory non-Hodgkin diffuse large B-cell lymphoma: results of a prospective, multicenter, phase II clinical trial. Haematologica. 2014 Mar;99(3):505-10. Epub 2013 Oct 25. [http://www.haematologica.org/content/99/3/505.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943314/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24162789 PubMed]
+#'''SHEBA-07-4466-AN-CTIL:''' Shimoni A, Avivi I, Rowe JM, Yeshurun M, Levi I, Or R, Patachenko P, Avigdor A, Zwas T, Nagler A. A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma. Cancer. 2012 Oct 1;118(19):4706-14. Epub 2012 Jan 17. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.27418/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22252613 PubMed]
-# '''ZBEAM2:''' Fruchart C, Tilly H, Morschhauser F, Ghesquières H, Bouteloup M, Fermé C, Van Den Neste E, Bordessoule D, Bouabdallah R, Delmer A, Casasnovas RO, Ysebaert L, Ciappuccini R, Briere J, Gisselbrecht C. Upfront consolidation combining yttrium-90 ibritumomab tiuxetan and high-dose therapy with stem cell transplantation in poor-risk patients with diffuse large B cell lymphoma. Biol Blood Marrow Transplant. 2014 Dec;20(12):1905-11. Epub 2014 Jul 26. [http://www.bbmt.org/article/S1083-8791(14)00473-X/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25072780 PubMed]
+#'''GELTAMO Z-BEAM LDCGB:''' Briones J, Novelli S, García-Marco JA, Tomás JF, Bernal T, Grande C, Canales MA, Torres A, Moraleda JM, Panizo C, Jarque I, Palmero F, Hernández M, González-Barca E, López D, Caballero D. Autologous stem cell transplantation after conditioning with Yttrium-90 ibritumomab tiuxetan plus beam in refractory non-Hodgkin diffuse large B-cell lymphoma: results of a prospective, multicenter, phase II clinical trial. Haematologica. 2014 Mar;99(3):505-10. Epub 2013 Oct 25. [http://www.haematologica.org/content/99/3/505.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943314/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24162789 PubMed]
+#'''ZBEAM2:''' Fruchart C, Tilly H, Morschhauser F, Ghesquières H, Bouteloup M, Fermé C, Van Den Neste E, Bordessoule D, Bouabdallah R, Delmer A, Casasnovas RO, Ysebaert L, Ciappuccini R, Briere J, Gisselbrecht C. Upfront consolidation combining yttrium-90 ibritumomab tiuxetan and high-dose therapy with stem cell transplantation in poor-risk patients with diffuse large B cell lymphoma. Biol Blood Marrow Transplant. 2014 Dec;20(12):1905-11. Epub 2014 Jul 26. [http://www.bbmt.org/article/S1083-8791(14)00473-X/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25072780 PubMed]
 =Maintenance after upfront therapy=
@@ Line 2,415: / Line 2,628: @@
 ===Regimen variant #1, 1 year {{#subobject:085502|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5214342/ Reddy et al. 2016 (VICC HEM 0835)]
-|style="background-color:#1a9851"|Randomized Phase II (E-de-esc)
+| style="background-color:#1a9851" |Randomized Phase II (E-de-esc)
 |Lenalidomide & Rituximab
-|style="background-color:#ffffbf"|Did not meet primary endpoint of RFS12
+| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS12
 |-
 |}
 ====Preceding treatment====
 *[[#R-CHOP|R-CHOP]] with or without radiation
 ====Chemotherapy====
 *[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
@@ Line 2,435: / Line 2,651: @@
 ===Regimen variant #2, 2 years {{#subobject:9e4448|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://ascopubs.org/doi/full/10.1200/JCO.2017.72.6984 Thieblemont et al. 2017 (REMARC)]
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#1a9851" |Phase III (E-esc)
 |[[#Observation|Observation]]
-|style="background-color:#91cf60"|Seems to have superior PFS
+| style="background-color:#91cf60" |Seems to have superior PFS
 |-
 |}
 ====Preceding treatment====
 *[[#R-CHOP|R-CHOP-21]] or [[#R-CHOP-14|R-CHOP14]]
 ====Chemotherapy====
 *[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
@@ Line 2,454: / Line 2,673: @@
 ===References===
-# '''VICC HEM 0835:''' Reddy NM, Greer JP, Morgan DS, Chen H, Park SI, Richards KL. A phase II randomized study of lenalidomide or lenalidomide and rituximab as maintenance therapy following standard chemotherapy for patients with high/high-intermediate risk diffuse large B-cell lymphoma. Leukemia. 2017 Jan;31(1):241-244. Epub 2016 Sep 22. [https://www.nature.com/leu/journal/v31/n1/full/leu2016255a.html link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5214342/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27654851 PubMed]
+#'''VICC HEM 0835:''' Reddy NM, Greer JP, Morgan DS, Chen H, Park SI, Richards KL. A phase II randomized study of lenalidomide or lenalidomide and rituximab as maintenance therapy following standard chemotherapy for patients with high/high-intermediate risk diffuse large B-cell lymphoma. Leukemia. 2017 Jan;31(1):241-244. Epub 2016 Sep 22. [https://www.nature.com/leu/journal/v31/n1/full/leu2016255a.html link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5214342/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27654851 PubMed]
 <!-- # '''Abstract:''' Catherine Thieblemont, Hervé Tilly, Maria Gomez da Silva, Rene-Olivier Casasnovas, Christophe Fruchart, Franck Morschhauser, Corinne Haioun, Julien Lazarovici, Sebastian Grosicki, Aurore Perrot, Judith Trotman, Catherine Sebban, Dolores Caballero, Richard Greil, Koen Van Eygen, Josette Briere, Jose Cabecadas, Gilles Andre Salles, Philippe Gaulard, Andre Bosly and Bertrand Coiffier. First Analysis of an International Double-Blind Randomized Phase III Study of Lenalidomide Maintenance in Elderly Patients with DLBCL Treated with R-CHOP in First Line, the Remarc Study from Lysa. Blood 2016 128:471 [http://www.bloodjournal.org/content/128/22/471 link to abstract] -->
-# '''REMARC:''' Thieblemont C, Tilly H, Gomes da Silva M, Casasnovas RO, Fruchart C, Morschhauser F, Haioun C, Lazarovici J, Grosicka A, Perrot A, Trotman J, Sebban C, Caballero D, Greil R, van Eygen K, Cohen AM, Gonzalez H, Bouabdallah R, Oberic L, Corront B, Choufi B, Lopez-Guillermo A, Catalano J, Van Hoof A, Briere J, Cabeçadas J, Salles G, Gaulard P, Bosly A, Coiffier B. Lenalidomide maintenance compared with placebo in responding elderly patients with diffuse large B-cell lymphoma treated with first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol. 2017 Aug 1;35(22):2473-2481. Epub 2017 Apr 20. [https://ascopubs.org/doi/full/10.1200/JCO.2017.72.6984 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28426350 PubMed]
+#'''REMARC:''' Thieblemont C, Tilly H, Gomes da Silva M, Casasnovas RO, Fruchart C, Morschhauser F, Haioun C, Lazarovici J, Grosicka A, Perrot A, Trotman J, Sebban C, Caballero D, Greil R, van Eygen K, Cohen AM, Gonzalez H, Bouabdallah R, Oberic L, Corront B, Choufi B, Lopez-Guillermo A, Catalano J, Van Hoof A, Briere J, Cabeçadas J, Salles G, Gaulard P, Bosly A, Coiffier B. Lenalidomide maintenance compared with placebo in responding elderly patients with diffuse large B-cell lymphoma treated with first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol. 2017 Aug 1;35(22):2473-2481. Epub 2017 Apr 20. [https://ascopubs.org/doi/full/10.1200/JCO.2017.72.6984 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28426350 PubMed]
 ==Rituximab monotherapy {{#subobject:c28fe4|Regimen=1}}==
@@ Line 2,466: / Line 2,686: @@
 ===Regimen variant #1 {{#subobject:da32ff|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4486230/ Jaeger et al. 2015 (NHL13)]
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#1a9851" |Phase III (E-esc)
 |[[#Observation|Observation]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of EFS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 |-
 |}
 ''Patients required to be in CR or CRu prior to enrollment. The protocol was amended after the first 69 patients enrolled to increase length of treatment from 1 to 2 years.''
 ====Preceding treatment====
 *Rituximab (375 mg/m<sup>2</sup>) x 8 and 4 to 8 cycles of CHOP-like chemotherapy
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 2,487: / Line 2,710: @@
 ===Regimen variant #2 {{#subobject:6c6458|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/bjh.13652/full Witzens-Harig et al. 2015 (HD2002)]
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#1a9851" |Phase III (E-esc)
 |[[#Observation|Observation]]
-|style="background-color:#1a9850"|Superior OS in males
+| style="background-color:#1a9850" |Superior OS in males
 |-
 |}
 ====Preceding treatment====
 *"Standard treatment" which was not further described in the paper, beyond that a majority of patient received R-CHOP (see Tables)
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 2,507: / Line 2,733: @@
 ===Regimen variant #3 {{#subobject:7c3ba2|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://annonc.oxfordjournals.org/content/20/12/1985.long Haioun et al. 2009 (LNH 98-3)]
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#1a9851" |Phase III (E-esc)
 |[[#Observation|Observation]]
-|style="background-color:#d9ef8b"|Might have superior EFS
+| style="background-color:#d9ef8b" |Might have superior EFS
 |-
 |}
 ====Preceding treatment====
 *[[#CBVM.2C_then_auto_HSCT|CBVM, then auto HSCT]]
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
@@ Line 2,527: / Line 2,756: @@
 ===Regimen variant #4 {{#subobject:8afe47|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://jco.ascopubs.org/content/24/19/3121.long Habermann et al. 2006 (ECOG E4494/CALGB 9793)]
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#1a9851" |Phase III (E-esc)
 |[[#Observation|Observation]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of FFS
@@ Line 2,540: / Line 2,769: @@
 ''Note: in ECOG E4494/CALGB 9793, rituximab maintenance had superior FFS in the group receiving [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]] upfront, which is no longer standard of care.''
 ====Preceding treatment====
 *[[#R-CHOP|R-CHOP]] versus [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]]
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
@@ Line 2,547: / Line 2,779: @@
 ===References===
-# '''ECOG E4494/CALGB 9793:''' Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, Dakhil SR, Woda B, Fisher RI, Peterson BA, Horning SJ. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006 Jul 1;24(19):3121-7. Epub 2006 Jun 5. [http://jco.ascopubs.org/content/24/19/3121.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16754935 PubMed]
-# '''LNH 98-3:''' Haioun C, Mounier N, Emile JF, Ranta D, Coiffier B, Tilly H, Récher C, Fermé C, Gabarre J, Herbrecht R, Morchhauser F, Gisselbrecht C. Rituximab versus observation after high-dose consolidative first-line chemotherapy with autologous stem-cell transplantation in patients with poor-risk diffuse large B-cell lymphoma. Ann Oncol. 2009 Dec;20(12):1985-92. Epub 2009 Jun 30. [http://annonc.oxfordjournals.org/content/20/12/1985.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19567453 PubMed]
+#'''ECOG E4494/CALGB 9793:''' Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, Dakhil SR, Woda B, Fisher RI, Peterson BA, Horning SJ. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006 Jul 1;24(19):3121-7. Epub 2006 Jun 5. [http://jco.ascopubs.org/content/24/19/3121.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16754935 PubMed]
+#'''LNH 98-3:''' Haioun C, Mounier N, Emile JF, Ranta D, Coiffier B, Tilly H, Récher C, Fermé C, Gabarre J, Herbrecht R, Morchhauser F, Gisselbrecht C. Rituximab versus observation after high-dose consolidative first-line chemotherapy with autologous stem-cell transplantation in patients with poor-risk diffuse large B-cell lymphoma. Ann Oncol. 2009 Dec;20(12):1985-92. Epub 2009 Jun 30. [http://annonc.oxfordjournals.org/content/20/12/1985.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19567453 PubMed]
 <!-- These data have been presented in part at the 55th Annual Meeting of the American Society of Hematology, New Orleans 2013, the 12th International Conference on Malignant Lymphoma 2013, Lugano, and the 18th Congress of the European Hematology Association, Stockholm 2013. -->
-# '''NHL13:''' Jaeger U, Trneny M, Melzer H, Praxmarer M, Nawarawong W, Ben Yehuda D, Goldstein D, Mihaljevic B, Ilhan O, Ballova V, Hedenus M, Hsiao LT, Au WY, Burgstaller S, Weidinger G, Keil F, Dittrich C, Skrabs C, Klingler A, Chott A, Fridrik MA, Greil R. Rituximab maintenance for patients with aggressive B-cell lymphoma in first remission: results of the randomized NHL13 trial. Haematologica. 2015 Jul;100(7):955-63. Epub 2015 Apr 24. [http://www.haematologica.org/content/100/7/955 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4486230/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25911553 PubMed]
+#'''NHL13:''' Jaeger U, Trneny M, Melzer H, Praxmarer M, Nawarawong W, Ben Yehuda D, Goldstein D, Mihaljevic B, Ilhan O, Ballova V, Hedenus M, Hsiao LT, Au WY, Burgstaller S, Weidinger G, Keil F, Dittrich C, Skrabs C, Klingler A, Chott A, Fridrik MA, Greil R. Rituximab maintenance for patients with aggressive B-cell lymphoma in first remission: results of the randomized NHL13 trial. Haematologica. 2015 Jul;100(7):955-63. Epub 2015 Apr 24. [http://www.haematologica.org/content/100/7/955 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4486230/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25911553 PubMed]
-# '''HD2002:''' Witzens-Harig M, Benner A, McClanahan F, Klemmer J, Brandt J, Brants E, Rieger M, Meissner J, Hensel M, Neben K, Dreger P, Lengfelder E, Schmidt-Wolf I, Krämer A, Ho AD. Rituximab maintenance improves survival in male patients with diffuse large B-cell lymphoma: results of the HD2002 prospective multicentre randomized phase III trial. Br J Haematol. 2015 Dec;171(5):710-9. Epub 2015 Oct 9. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13652/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26449739 PubMed]
+#'''HD2002:''' Witzens-Harig M, Benner A, McClanahan F, Klemmer J, Brandt J, Brants E, Rieger M, Meissner J, Hensel M, Neben K, Dreger P, Lengfelder E, Schmidt-Wolf I, Krämer A, Ho AD. Rituximab maintenance improves survival in male patients with diffuse large B-cell lymphoma: results of the HD2002 prospective multicentre randomized phase III trial. Br J Haematol. 2015 Dec;171(5):710-9. Epub 2015 Oct 9. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13652/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26449739 PubMed]
 =Relapsed or refractory, salvage therapy=
@@ Line 2,564: / Line 2,797: @@
 ===Regimen {{#subobject:294f6d|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3724189/ Matasar et al. 2013 (GSK 110927)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[https://ascopubs.org/doi/full/10.1200/JCO.2016.69.0198 van Imhoff et al. 2016 (ORCHARRD)]
-|style="background-color:#1a9851"|Phase III (E-switch-ic)
+| style="background-color:#1a9851" |Phase III (E-switch-ic)
 |[[#R-DHAP|R-DHAP]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 |-
 |}
 ====Chemotherapy====
 *[[Ofatumumab (Arzerra)]] as follows:
 **Cycle 1: 1000 mg IV once per day on days 1 & 8
@@ Line 2,589: / Line 2,823: @@
 ====Supportive medications====
 *GSK 110927 recommended: [[Filgrastim (Neupogen)]] or [[Pegfilgrastim (Neulasta)]]
 '''21-day cycle for 3 cycles'''
 ====Subsequent treatment====
-*GSK 110927, responders: Stem-cell mobilization and autologous hematopoietic stem cell transplant (regimen not specified)
+*GSK 110927, responders: Stem-cell mobilization and autologous hematopoietic stem cell transplant (regimen not specified)
 *ORCHARRD, responders: [[#BEAM.2C_then_auto_HSCT|BEAM with autologous hematopoietic stem cell transplant]] except those in Japan who received [[#LEED.2C_then_auto_HSCT|LEED with autologous hematopoietic stem cell transplant]]
 ===References===
 <!-- Presented at the 2011 American Society of Hematology Annual Meeting, San Diego, CA, December 10-13, 2011. -->
-# '''GSK 110927:''' Matasar MJ, Czuczman MS, Rodriguez MA, Fennessy M, Shea TC, Spitzer G, Lossos IS, Kharfan-Dabaja MA, Joyce R, Fayad L, Henkel K, Liao Q, Edvardsen K, Jewell RC, Fecteau D, Singh RP, Lisby S, Moskowitz CH. Ofatumumab in combination with ICE or DHAP chemotherapy in relapsed or refractory intermediate grade B-cell lymphoma. Blood. 2013 Jul 25;122(4):499-506. Epub 2013 May 21. [http://www.bloodjournal.org/content/122/4/499.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3724189/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23692856 PubMed]
-# '''ORCHARRD:''' van Imhoff GW, McMillan A, Matasar MJ, Radford J, Ardeshna KM, Kuliczkowski K, Kim W, Hong X, Goerloev JS, Davies A, Barrigón MD, Ogura M, Leppä S, Fennessy M, Liao Q, van der Holt B, Lisby S, Hagenbeek A. Ofatumumab versus rituximab salvage chemoimmunotherapy in relapsed or refractory diffuse large B-cell lymphoma: The ORCHARRD study. J Clin Oncol. 2017 Feb 10;35(5):544-51. Epub 2016 Dec 28. [https://ascopubs.org/doi/full/10.1200/JCO.2016.69.0198 link to original article] [https://ascopubs.org/doi/suppl/10.1200/JCO.2016.69.0198/suppl_file/ds_2016.690198.pdf link to data supplement] '''verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/28029326 PubMed]
+#'''GSK 110927:''' Matasar MJ, Czuczman MS, Rodriguez MA, Fennessy M, Shea TC, Spitzer G, Lossos IS, Kharfan-Dabaja MA, Joyce R, Fayad L, Henkel K, Liao Q, Edvardsen K, Jewell RC, Fecteau D, Singh RP, Lisby S, Moskowitz CH. Ofatumumab in combination with ICE or DHAP chemotherapy in relapsed or refractory intermediate grade B-cell lymphoma. Blood. 2013 Jul 25;122(4):499-506. Epub 2013 May 21. [http://www.bloodjournal.org/content/122/4/499.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3724189/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23692856 PubMed]
+#'''ORCHARRD:''' van Imhoff GW, McMillan A, Matasar MJ, Radford J, Ardeshna KM, Kuliczkowski K, Kim W, Hong X, Goerloev JS, Davies A, Barrigón MD, Ogura M, Leppä S, Fennessy M, Liao Q, van der Holt B, Lisby S, Hagenbeek A. Ofatumumab versus rituximab salvage chemoimmunotherapy in relapsed or refractory diffuse large B-cell lymphoma: The ORCHARRD study. J Clin Oncol. 2017 Feb 10;35(5):544-51. Epub 2016 Dec 28. [https://ascopubs.org/doi/full/10.1200/JCO.2016.69.0198 link to original article] [https://ascopubs.org/doi/suppl/10.1200/JCO.2016.69.0198/suppl_file/ds_2016.690198.pdf link to data supplement] '''verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/28029326 PubMed]
 ==O-ICE {{#subobject:f3f288|Regimen=1}}==
@@ Line 2,610: / Line 2,847: @@
 ===Regimen {{#subobject:abb23b|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3724189/ Matasar et al. 2013 (GSK 110927)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''Note: Subsequent consolidation therapy was not specified.''
 ====Chemotherapy====
 *[[Ofatumumab (Arzerra)]] as follows:
 **Cycle 1: 1000 mg IV once per day on days 1 & 8
@@ Line 2,628: / Line 2,866: @@
 ====Supportive medications====
 *[[Mesna (Mesnex)]] 5000 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 2, '''mixed with [[Ifosfamide (Ifex)]]'''
 *Recommended: [[Filgrastim (Neupogen)]] or [[Pegfilgrastim (Neulasta)]]
@@ Line 2,635: / Line 2,874: @@
 ===References===
 <!-- Presented at the 2011 American Society of Hematology Annual Meeting, San Diego, CA, December 10-13, 2011. -->
-# '''GSK 110927:''' Matasar MJ, Czuczman MS, Rodriguez MA, Fennessy M, Shea TC, Spitzer G, Lossos IS, Kharfan-Dabaja MA, Joyce R, Fayad L, Henkel K, Liao Q, Edvardsen K, Jewell RC, Fecteau D, Singh RP, Lisby S, Moskowitz CH. Ofatumumab in combination with ICE or DHAP chemotherapy in relapsed or refractory intermediate grade B-cell lymphoma. Blood. 2013 Jul 25;122(4):499-506. Epub 2013 May 21. [http://www.bloodjournal.org/content/122/4/499.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3724189/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23692856 PubMed]
+#'''GSK 110927:''' Matasar MJ, Czuczman MS, Rodriguez MA, Fennessy M, Shea TC, Spitzer G, Lossos IS, Kharfan-Dabaja MA, Joyce R, Fayad L, Henkel K, Liao Q, Edvardsen K, Jewell RC, Fecteau D, Singh RP, Lisby S, Moskowitz CH. Ofatumumab in combination with ICE or DHAP chemotherapy in relapsed or refractory intermediate grade B-cell lymphoma. Blood. 2013 Jul 25;122(4):499-506. Epub 2013 May 21. [http://www.bloodjournal.org/content/122/4/499.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3724189/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23692856 PubMed]
 ==R-DexaBEAM {{#subobject:81a0a4|Regimen=1}}==
@@ Line 2,646: / Line 2,886: @@
 ===Regimen {{#subobject:801417|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/bjh.13234/full Kirschey et al. 2014 (Mz-135)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''Note: the dosing in the manuscript is different than below. The below are the correct doses as verified by the authors.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1 & 8
 *[[Dexamethasone (Decadron)]] 8 mg PO three times per day on days 1 to 10
@@ Line 2,664: / Line 2,905: @@
 '''3- to 4-week cycle for 2 cycles'''
 ====Subsequent treatment====
 *[[#R-BEAM.2C_then_auto_HSCT|R-BEAM with autologous hematopoietic stem cell transplant]] or [[#R-TBI.2FCy.2C_then_auto_HSCT|R-TBI/Cy with autologous hematopoietic stem cell transplant]]
 ===References===
-# '''Mz-135:''' Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13234/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25546611 PubMed]
+#'''Mz-135:''' Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13234/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25546611 PubMed]
 ==R-DHAOx {{#subobject:0d0c67|Regimen=1}}==
@@ Line 2,678: / Line 2,921: @@
 ===Regimen {{#subobject:962cf0|Variant=1}}===
 {| class="wikitable" style="width: 75%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 33%" |Study
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
+! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1002/ajh.24824/full Witzig et al. 2017 (MCCRC MC0485)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 | style="background-color:#bfd3e6" |ORR: 71% (95% CI, 56–84)
 |-
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] as follows:
 **Cycle 1 only: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
@@ Line 2,696: / Line 2,940: @@
 ====Supportive medications====
 *[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 4
 '''21-day cycles'''
 ====Subsequent treatment====
 *Most responders proceeded to high-dose chemotherapy with autologous hematopoietic stem cell transplant after 2 cycles, although this was not mandated in the protocol
 ===References===
-# '''MCCRC MC0485:''' Witzig TE, Johnston PB, LaPlant BR, Kurtin PJ, Pederson LD, Moore DF Jr, Nabbout NH, Nikcevich DA, Rowland KM, Grothey A. Long-term follow-up of chemoimmunotherapy with rituximab, oxaliplatin, cytosine arabinoside, dexamethasone (ROAD) in patients with relapsed CD20+ B-cell non-Hodgkin lymphoma: Results of a study of the Mayo Clinic Cancer Center Research Consortium (MCCRC) MC0485 now known as academic and community cancer research united (ACCRU). Am J Hematol. 2017 Oct;92(10):1004-1010. Epub 2017 Aug 17. [https://onlinelibrary.wiley.com/doi/10.1002/ajh.24824/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28614905 PubMed]
+#'''MCCRC MC0485:''' Witzig TE, Johnston PB, LaPlant BR, Kurtin PJ, Pederson LD, Moore DF Jr, Nabbout NH, Nikcevich DA, Rowland KM, Grothey A. Long-term follow-up of chemoimmunotherapy with rituximab, oxaliplatin, cytosine arabinoside, dexamethasone (ROAD) in patients with relapsed CD20+ B-cell non-Hodgkin lymphoma: Results of a study of the Mayo Clinic Cancer Center Research Consortium (MCCRC) MC0485 now known as academic and community cancer research united (ACCRU). Am J Hematol. 2017 Oct;92(10):1004-1010. Epub 2017 Aug 17. [https://onlinelibrary.wiley.com/doi/10.1002/ajh.24824/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28614905 PubMed]
 ==R-DHAP {{#subobject:18c266|Regimen=1}}==
@@ Line 2,714: / Line 2,961: @@
 ===Regimen variant #1 {{#subobject:af0858|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664033/ Gisselbrecht et al. 2010 (CORAL)]
-|style="background-color:#1a9851"|Phase III (E-switch-ic)
+| style="background-color:#1a9851" |Phase III (E-switch-ic)
 |[[#R-ICE|R-ICE]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of mobilization-adjusted response rate after 3 cycles
+| style="background-color:#ffffbf" |Did not meet primary endpoint of mobilization-adjusted response rate after 3 cycles
 |-
 |[https://ascopubs.org/doi/full/10.1200/JCO.2016.69.0198 van Imhoff et al. 2016 (ORCHARRD)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#O-DHAP|O-DHAP]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 |-
 |}
 ''Note: '''CORAL''' makes reference to Velasquez et al. 1988 to describe this regimen, although this reference is for DHAP, not R-DHAP. The paper also contains the following regimen information:''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] as follows, '''given first''':
 **Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days -1 & 1 ('''CORAL''') or days 1 & 8 ('''ORCHARRD''')
 **Cycle 2: 375 mg/m<sup>2</sup> IV once on day 1
 *[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 *[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on day 2 (total dose per cycle: 4000 mg/m<sup>2</sup>)
@@ Line 2,740: / Line 2,988: @@
 ====Supportive medications====
 *'''CORAL''': [[Filgrastim (Neupogen) | G-CSF]] "depending on site policy, with R-DHAP, but always after the third cycle until the end of leukaphereses"
 '''21-day cycle for 3 cycles'''
 ====Subsequent treatment====
 *CORAL, responders: [[#BEAM.2C_then_auto_HSCT|BEAM with autologous hematopoietic stem cell transplant]]
 *ORCHARRD, responders: [[#BEAM.2C_then_auto_HSCT|BEAM with autologous hematopoietic stem cell transplant]] except those in Japan who received [[#LEED.2C_then_auto_HSCT|LEED with autologous hematopoietic stem cell transplant]]
@@ Line 2,749: / Line 2,999: @@
 ===Regimen variant #2 {{#subobject:ac829f|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://jco.ascopubs.org/content/32/31/3490.full Crump et al. 2014 (NCIC-CTG LY.12)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#R-GDP|R-GDP]]
-|style="background-color:#eeee01"|Non-inferior RR after 2 cycles
+| style="background-color:#eeee01" |Non-inferior RR after 2 cycles
 |-
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
@@ Line 2,768: / Line 3,019: @@
 '''21-day cycle for up to 3 cycles'''
 ====Subsequent treatment====
 *Responders: Stem-cell mobilization and high-dose chemotherapy with autologous hematopoietic stem cell transplant (regimen not specified)
 ===Regimen variant #3 {{#subobject:65859a|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.tandfonline.com/doi/full/10.1080/07357900600814490 Mey et al. 2006]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''The doses here were used after a mid-protocol amendment pertaining to the first cycle.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Dexamethasone (Decadron)]] as follows:
@@ Line 2,790: / Line 3,043: @@
 ***Older than 60 years: 500 mg/m<sup>2</sup> IV over 2 hours every 12 hours on day 4 (total dose per cycle: 1000 mg/m<sup>2</sup>)
 **Cycles 2 to 4 as follows:
 ***Younger than 60 years: 2000 mg/m<sup>2</sup> IV over 2 hours every 12 hours on day 4 (total dose per cycle: 4000 mg/m<sup>2</sup>)
 ***Older than 60 years: 1000 mg/m<sup>2</sup> IV over 2 hours every 12 hours on day 4 (total dose per cycle: 2000 mg/m<sup>2</sup>)
 *[[Cisplatin (Platinol)]] as follows:
@@ Line 2,798: / Line 3,051: @@
 '''21-day cycle for up to 4 cycles'''
 ====Subsequent treatment====
 *Patients with at least PR were allowed to undergo high-dose chemotherapy with autologous stem-cell transplant (regimen not specified)
 ===References===
-# Mey UJ, Orlopp KS, Flieger D, Strehl JW, Ho AD, Hensel M, Bopp C, Gorschlüter M, Wilhelm M, Birkmann J, Kaiser U, Neubauer A, Florschütz A, Rabe C, Hahn C, Glasmacher AG, Schmidt-Wolf IG. Dexamethasone, high-dose cytarabine, and cisplatin in combination with rituximab as salvage treatment for patients with relapsed or refractory aggressive non-Hodgkin's lymphoma. Cancer Invest. 2006 Oct;24(6):593-600. [https://www.tandfonline.com/doi/full/10.1080/07357900600814490 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16982464 PubMed]
+#Mey UJ, Orlopp KS, Flieger D, Strehl JW, Ho AD, Hensel M, Bopp C, Gorschlüter M, Wilhelm M, Birkmann J, Kaiser U, Neubauer A, Florschütz A, Rabe C, Hahn C, Glasmacher AG, Schmidt-Wolf IG. Dexamethasone, high-dose cytarabine, and cisplatin in combination with rituximab as salvage treatment for patients with relapsed or refractory aggressive non-Hodgkin's lymphoma. Cancer Invest. 2006 Oct;24(6):593-600. [https://www.tandfonline.com/doi/full/10.1080/07357900600814490 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16982464 PubMed]
 <!-- # Hagberg H, Gisselbrecht C; CORAL study group. Randomised phase III study of R-ICE versus R-DHAP in relapsed patients with CD20 diffuse large B-cell lymphoma (DLBCL) followed by high-dose therapy and a second randomisation to maintenance treatment with rituximab or not: an update of the CORAL study. Ann Oncol. 2006 May;17 Suppl 4:iv31-2. [http://annonc.oxfordjournals.org/content/17/suppl_4/iv31.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16702182 PubMed]
 # Presented at the 45th Annual Meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL, and at the 51st Annual Meeting of the American Society of Hematology, December 5-8, 2009, New Orleans, LA. -->
-# '''CORAL:''' Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Brière J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. Epub 2010 Jul 26. Erratum in: J Clin Oncol. 2012 May 20;30(15):1896. [http://jco.ascopubs.org/content/28/27/4184.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664033/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20660832 PubMed]
+#'''CORAL:''' Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Brière J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. Epub 2010 Jul 26. Erratum in: J Clin Oncol. 2012 May 20;30(15):1896. [http://jco.ascopubs.org/content/28/27/4184.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664033/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20660832 PubMed]
 <!-- Presented in part at the Annual Meeting of the American Society of Hematology, Atlanta, GA, December 7-10, 2013, and the International Conference on Malignant Lymphoma, Lugano, Switzerland, June 19-22, 2013. -->
-# '''NCIC-CTG LY.12:''' Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. [http://jco.ascopubs.org/content/32/31/3490.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25267740 PubMed]
+#'''NCIC-CTG LY.12:''' Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. [http://jco.ascopubs.org/content/32/31/3490.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25267740 PubMed]
-# '''ORCHARRD:''' van Imhoff GW, McMillan A, Matasar MJ, Radford J, Ardeshna KM, Kuliczkowski K, Kim W, Hong X, Goerloev JS, Davies A, Barrigón MD, Ogura M, Leppä S, Fennessy M, Liao Q, van der Holt B, Lisby S, Hagenbeek A. Ofatumumab versus rituximab salvage chemoimmunotherapy in relapsed or refractory diffuse large B-cell lymphoma: the ORCHARRD study. J Clin Oncol. 2017 Feb 10;35(5):544-51. Epub 2016 Dec 28. [https://ascopubs.org/doi/full/10.1200/JCO.2016.69.0198 link to original article] [https://ascopubs.org/doi/suppl/10.1200/JCO.2016.69.0198/suppl_file/ds_2016.690198.pdf link to data supplement] '''verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/28029326 PubMed]
+#'''ORCHARRD:''' van Imhoff GW, McMillan A, Matasar MJ, Radford J, Ardeshna KM, Kuliczkowski K, Kim W, Hong X, Goerloev JS, Davies A, Barrigón MD, Ogura M, Leppä S, Fennessy M, Liao Q, van der Holt B, Lisby S, Hagenbeek A. Ofatumumab versus rituximab salvage chemoimmunotherapy in relapsed or refractory diffuse large B-cell lymphoma: the ORCHARRD study. J Clin Oncol. 2017 Feb 10;35(5):544-51. Epub 2016 Dec 28. [https://ascopubs.org/doi/full/10.1200/JCO.2016.69.0198 link to original article] [https://ascopubs.org/doi/suppl/10.1200/JCO.2016.69.0198/suppl_file/ds_2016.690198.pdf link to data supplement] '''verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/28029326 PubMed]
 ==R-DHAP/R-VIM {{#subobject:e57948|Regimen=1}}==
@@ Line 2,817: / Line 3,072: @@
 ===Protocol {{#subobject:f46b7f|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://www.bloodjournal.org/content/111/2/537.long Vellenga et al. 2008 (HOVON-44)]
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#1a9851" |Phase III (E-esc)
 |DHAP/VIM
-|style="background-color:#1a9850"|Superior PFS
+| style="background-color:#1a9850" |Superior PFS
 |-
 |}
 ''Note: per the paper, "in case patients were non-responsive to R-DHAP but responsive to R-VIM, it was allowed to repeat the R-VIM regimen as the third cycle of reinduction chemotherapy." No statement is made as to whether Mesna is used in the VIM protocol.''
 ====Chemotherapy, R-DHAP portion====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 5
 *[[Dexamethasone (Decadron)]] 40 mg IV or PO once per day on days 1 to 4
@@ Line 2,838: / Line 3,094: @@
 ====Chemotherapy, R-VIM portion====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 6
 *[[Etoposide (Vepesid)]] 90 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
@@ Line 2,845: / Line 3,102: @@
 '''28-day cycle for 1 cycle, given in-between R-DHAP cycles'''
 ====Subsequent treatment====
 *Responders: Stem-cell mobilization, then [[#BEAM.2C_then_auto_HSCT|BEAM with autologous hematopoietic stem cell transplant]]
 ===References===
-# Vellenga E, van Putten WL, van 't Veer MB, Zijlstra JM, Fibbe WE, van Oers MH, Verdonck LF, Wijermans PW, van Imhoff GW, Lugtenburg PJ, Huijgens PC. Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20+ NHL: a prospective randomized HOVON trial. Blood. 2008 Jan 15;111(2):537-43. [http://www.bloodjournal.org/content/111/2/537.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17971487 PubMed]
+#Vellenga E, van Putten WL, van 't Veer MB, Zijlstra JM, Fibbe WE, van Oers MH, Verdonck LF, Wijermans PW, van Imhoff GW, Lugtenburg PJ, Huijgens PC. Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20+ NHL: a prospective randomized HOVON trial. Blood. 2008 Jan 15;111(2):537-43. [http://www.bloodjournal.org/content/111/2/537.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17971487 PubMed]
 ==R-EPOCH {{#subobject:ddfe7d|Regimen=1}}==
@@ Line 2,859: / Line 3,118: @@
 ===Regimen {{#subobject:a10d44|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://annonc.oxfordjournals.org/content/15/3/511.long Jermann et al. 2004]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''Note: this is not the dose-adjusted R-EPOCH regimen''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Etoposide (Vepesid)]] 65 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 2 (total dose per cycle: 195 mg/m<sup>2</sup>)
 *[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day PO on days 1 to 14
 *[[Vincristine (Oncovin)]] 0.5 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 2 (total dose per cycle: 1.5 mg/m<sup>2</sup>)
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 5
 *[[Doxorubicin (Adriamycin)]] 15 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 2 (total dose per cycle: 45 mg/m<sup>2</sup>)
@@ Line 2,877: / Line 3,137: @@
 '''21-day cycle for 4 to 6 cycles'''
 ====Subsequent treatment====
 *Patients younger than 60 who achieved at least PR: High-dose chemotherapy with autologous hematopoietic stem-cell transplantation (regimen not specified)
 ===References===
-# Jermann M, Jost LM, Taverna Ch, Jacky E, Honegger HP, Betticher DC, Egli F, Kroner T, Stahel RA. Rituximab-EPOCH, an effective salvage therapy for relapsed, refractory or transformed B-cell lymphomas: results of a phase II study. Ann Oncol. 2004 Mar;15(3):511-6. [http://annonc.oxfordjournals.org/content/15/3/511.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14998858 PubMed]
+#Jermann M, Jost LM, Taverna Ch, Jacky E, Honegger HP, Betticher DC, Egli F, Kroner T, Stahel RA. Rituximab-EPOCH, an effective salvage therapy for relapsed, refractory or transformed B-cell lymphomas: results of a phase II study. Ann Oncol. 2004 Mar;15(3):511-6. [http://annonc.oxfordjournals.org/content/15/3/511.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14998858 PubMed]
 ==R-ESHAP {{#subobject:7794d|Regimen=1}}==
@@ Line 2,890: / Line 3,153: @@
 ===Regimen {{#subobject:b6038c|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://www.haematologica.org/content/93/12/1829.long Martín et al. 2008]
-|style="background-color:#ffffbe"|Retrospective
+| style="background-color:#ffffbe" |Retrospective
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(11)70097-0/fulltext Avilés et al. 2010]
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#1a9851" |Phase III (E-esc)
 |[[#ESHAP|ESHAP]]
-|style="background-color:#ffffbf"|Did not meet efficacy endpoints
+| style="background-color:#ffffbf" |Did not meet efficacy endpoints
 |-
 |}
 ''Regimen details are based on ESHAP paper from 1994. Per retrospective review (Martin et al. 2008), 90% of patients given R-ESHAP received rituximab on day 1, 10% on day 5.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1 (or day 5)
 *[[Etoposide (Vepesid)]] 40 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 4
@@ Line 2,916: / Line 3,180: @@
 ====Supportive medications====
 *At least 1 liter normal saline with 25 to 50 g [[Mannitol]] once per day throughout chemotherapy
 *[[Metoclopramide (Reglan)]] 0.5 to 1 mg/kg (route not specified) "given regularly"
@@ Line 2,922: / Line 3,187: @@
 ===References===
-# '''Retrospective:''' Martín A, Conde E, Arnan M, Canales MA, Deben G, Sancho JM, Andreu R, Salar A, García-Sanchez P, Vázquez L, Nistal S, Requena MJ, Donato EM, González JA, León A, Ruiz C, Grande C, González-Barca E, Caballero MD; Grupo Español de Linfomas/Trasplante Autólogo de Médula Osea (GEL/TAMO Cooperative Group). R-ESHAP as salvage therapy for patients with relapsed or refractory diffuse large B-cell lymphoma: the influence of prior exposure to rituximab on outcome. A GEL/TAMO study. Haematologica. 2008 Dec;93(12):1829-36. Epub 2008 Oct 22. [http://www.haematologica.org/content/93/12/1829.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18945747 PubMed]
-# Avilés A, Neri N, Huerta-Guzmán J, de Jesús Nambo M. ESHAP versus rituximab-ESHAP in frail patients with refractory diffuse large B-cell lymphoma. Clin Lymphoma Myeloma Leuk. 2010 Apr;10(2):125-8. [http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(11)70097-0/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20371445 PubMed]
+#'''Retrospective:''' Martín A, Conde E, Arnan M, Canales MA, Deben G, Sancho JM, Andreu R, Salar A, García-Sanchez P, Vázquez L, Nistal S, Requena MJ, Donato EM, González JA, León A, Ruiz C, Grande C, González-Barca E, Caballero MD; Grupo Español de Linfomas/Trasplante Autólogo de Médula Osea (GEL/TAMO Cooperative Group). R-ESHAP as salvage therapy for patients with relapsed or refractory diffuse large B-cell lymphoma: the influence of prior exposure to rituximab on outcome. A GEL/TAMO study. Haematologica. 2008 Dec;93(12):1829-36. Epub 2008 Oct 22. [http://www.haematologica.org/content/93/12/1829.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18945747 PubMed]
+#Avilés A, Neri N, Huerta-Guzmán J, de Jesús Nambo M. ESHAP versus rituximab-ESHAP in frail patients with refractory diffuse large B-cell lymphoma. Clin Lymphoma Myeloma Leuk. 2010 Apr;10(2):125-8. [http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(11)70097-0/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20371445 PubMed]
 ==R-GDP {{#subobject:a5d411|Regimen=1}}==
@@ Line 2,934: / Line 3,200: @@
 ===Regimen variant #1, 1 day of cisplatin/cycle {{#subobject:c6480d|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://jco.ascopubs.org/content/32/31/3490.full Crump et al. 2014 (NCIC-CTG LY.12)]
-|style="background-color:#1a9851"|Phase III (E-switch-ic)
+| style="background-color:#1a9851" |Phase III (E-switch-ic)
 |[[#R-DHAP|R-DHAP]]
-|style="background-color:#eeee01"|Non-inferior RR after 2 cycles
+| style="background-color:#eeee01" |Non-inferior RR after 2 cycles
 |-
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
@@ Line 2,953: / Line 3,220: @@
 '''21-day cycle for up to 3 cycles'''
 ====Subsequent treatment====
 *Responders: Stem-cell mobilization and high-dose chemotherapy with autologous hematopoietic stem cell transplant (regimen not specified)
 ===Regimen variant #2, 3 days of cisplatin/cycle {{#subobject:325d38|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://link.springer.com/article/10.1007%2Fs12032-012-0211-2 Hou et al. 2012]
-|style="background-color:#91cf61"|Non-randomized
+| style="background-color:#91cf61" |Non-randomized
 |-
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
@@ Line 2,973: / Line 3,242: @@
 ===References===
-# Hou Y, Wang HQ, Ba Y. Rituximab, gemcitabine, cisplatin, and dexamethasone in patients with refractory or relapsed aggressive B-cell lymphoma. Med Oncol. 2012 Dec;29(4):2409-16. Epub 2012 Apr 3. [http://link.springer.com/article/10.1007%2Fs12032-012-0211-2 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22476761 PubMed]
-# '''NCIC-CTG LY.12:''' Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. [http://jco.ascopubs.org/content/32/31/3490.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25267740 PubMed]
+#Hou Y, Wang HQ, Ba Y. Rituximab, gemcitabine, cisplatin, and dexamethasone in patients with refractory or relapsed aggressive B-cell lymphoma. Med Oncol. 2012 Dec;29(4):2409-16. Epub 2012 Apr 3. [http://link.springer.com/article/10.1007%2Fs12032-012-0211-2 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22476761 PubMed]
+#'''NCIC-CTG LY.12:''' Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. [http://jco.ascopubs.org/content/32/31/3490.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25267740 PubMed]
 ==R-ICE {{#subobject:117cd8|Regimen=1}}==
@@ Line 2,985: / Line 3,255: @@
 ===Regimen variant #1 {{#subobject:35e1ac|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664033/ Gisselbrecht et al. 2010 (CORAL)]
-|style="background-color:#1a9851"|Phase III (E-switch-ic)
+| style="background-color:#1a9851" |Phase III (E-switch-ic)
 |[[#R-DHAP|R-DHAP]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of mobilization-adjusted response rate after 3 cycles
+| style="background-color:#ffffbf" |Did not meet primary endpoint of mobilization-adjusted response rate after 3 cycles
 |-
 |[http://www.tandfonline.com/doi/full/10.3109/10428194.2015.1007504 Fayad et al. 2015 (SG040-0005)]
-|style="background-color:#1a9851"|Randomized Phase IIb (C)
+| style="background-color:#1a9851" |Randomized Phase IIb (C)
 |R-ICE + Dacetuzumab
-|style="background-color:#ffffbf"|Did not meet primary endpoint of CR rate
+| style="background-color:#ffffbf" |Did not meet primary endpoint of CR rate
 |-
 |}
 ''Note: Gisselbrecht et al. 2010 refers to the non-randomized regimen described in variant #3 below, although it has slightly different day numbering. Doses are the same.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] as follows (given first before other chemotherapy):
 **Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days -1 & 1
 **Cycles 2 & 3: 375 mg/m<sup>2</sup> IV once on day 1
 *[[Ifosfamide (Ifex)]] 5000 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 2
 *[[Carboplatin (Paraplatin)]] AUC 5 (maximum dose of 800 mg) IV once on day 2
@@ Line 3,011: / Line 3,282: @@
 ====Supportive medications====
 *[[Mesna (Mesnex)]] given with [[Ifosfamide (Ifex)]] (dose & schedule not specified)
 *"[[Filgrastim (Neupogen) | Granulocyte colony-stimulating factor]] was administered after R-ICE"
@@ Line 3,016: / Line 3,288: @@
 '''21-day cycle for 3 cycles'''
 ====Subsequent treatment====
 *CORAL with complete or partial response: [[#BEAM.2C_then_auto_HSCT|BEAM with autologous hematopoietic stem cell transplant]]
 ===Regimen variant #2 {{#subobject:871cdf|Variant=1}}===
 {| class="wikitable" style="width: 75%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 33%" |Study
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
+! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
 |[http://zhxyxzz.yiigle.com/zhxyxzz20143504/395338.htm Guo et al. 2014]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 | style="background-color:#e0ecf4" |ORR: 78%
 |-
@@ Line 3,031: / Line 3,304: @@
 ''Note: original article is in Chinese; this information is from the English abstract.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Ifosfamide (Ifex)]] 1600 mg/m<sup>2</sup> IV once per day on days 2 to 4
@@ Line 3,040: / Line 3,314: @@
 ===Regimen variant #3 {{#subobject:820b17|Variant=1}}===
 {| class="wikitable" style="width: 75%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 33%" |Study
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
+! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
 |[http://annonc.oxfordjournals.org/content/14/suppl_1/i5.long Zelenetz et al. 2003]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 | style="background-color:#e0ecf4" |ORR: 81% (*)
 |-
 |[http://www.bloodjournal.org/content/103/10/3684.long Kewalramani et al. 2004]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 | style="background-color:#e0ecf4" |ORR: 78% (*)
 |-
@@ Line 3,055: / Line 3,329: @@
 ''Third cycle intended to be followed by peripheral blood hematopoietic stem cell collection. ORR reported in Zelenetz et al. 2003 is for the subset of DLBCL patients who received R-ICE; it is unclear if these patients were exposed to rituximab previously. None of the patients in Kewalaramani et al. 2004 had previously received rituximab.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] as follows:
 **Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days -2 & 1
@@ Line 3,064: / Line 3,339: @@
 ====Supportive medications====
 *(as described by Kewalramani et al. 2004):
 *[[Mesna (Mesnex)]] 5000 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 4, '''mixed with [[Ifosfamide (Ifex)]]'''
@@ Line 3,073: / Line 3,349: @@
 ===References===
-# Zelenetz AD, Hamlin P, Kewalramani T, Yahalom J, Nimer S, Moskowitz CH. Ifosfamide, carboplatin, etoposide (ICE)-based second-line chemotherapy for the management of relapsed and refractory aggressive non-Hodgkin's lymphoma. Ann Oncol. 2003;14 Suppl 1:i5-10. [http://annonc.oxfordjournals.org/content/14/suppl_1/i5.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12736224 PubMed]
-# Kewalramani T, Zelenetz AD, Nimer SD, Portlock C, Straus D, Noy A, O'Connor O, Filippa DA, Teruya-Feldstein J, Gencarelli A, Qin J, Waxman A, Yahalom J, Moskowitz CH. Rituximab and ICE as second-line therapy before autologous stem cell transplantation for relapsed or primary refractory diffuse large B-cell lymphoma. Blood. 2004 May 15;103(10):3684-8. Epub 2004 Jan 22. [http://www.bloodjournal.org/content/103/10/3684.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14739217 PubMed]
+#Zelenetz AD, Hamlin P, Kewalramani T, Yahalom J, Nimer S, Moskowitz CH. Ifosfamide, carboplatin, etoposide (ICE)-based second-line chemotherapy for the management of relapsed and refractory aggressive non-Hodgkin's lymphoma. Ann Oncol. 2003;14 Suppl 1:i5-10. [http://annonc.oxfordjournals.org/content/14/suppl_1/i5.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12736224 PubMed]
+#Kewalramani T, Zelenetz AD, Nimer SD, Portlock C, Straus D, Noy A, O'Connor O, Filippa DA, Teruya-Feldstein J, Gencarelli A, Qin J, Waxman A, Yahalom J, Moskowitz CH. Rituximab and ICE as second-line therapy before autologous stem cell transplantation for relapsed or primary refractory diffuse large B-cell lymphoma. Blood. 2004 May 15;103(10):3684-8. Epub 2004 Jan 22. [http://www.bloodjournal.org/content/103/10/3684.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14739217 PubMed]
 <!-- # Hagberg H, Gisselbrecht C; CORAL study group. Randomised phase III study of R-ICE versus R-DHAP in relapsed patients with CD20 diffuse large B-cell lymphoma (DLBCL) followed by high-dose therapy and a second randomisation to maintenance treatment with rituximab or not: an update of the CORAL study. Ann Oncol. 2006 May;17 Suppl 4:iv31-2. [http://annonc.oxfordjournals.org/content/17/suppl_4/iv31.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16702182 PubMed]
 Presented at the 45th Annual Meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL, and at the 51st Annual Meeting of the American Society of Hematology, December 5-8, 2009, New Orleans, LA. -->
-# Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Brière J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. Epub 2010 Jul 26. Erratum in: J Clin Oncol. 2012 May 20;30(15):1896. [http://jco.ascopubs.org/content/28/27/4184.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664033/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20660832 PubMed]
+#Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Brière J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. Epub 2010 Jul 26. Erratum in: J Clin Oncol. 2012 May 20;30(15):1896. [http://jco.ascopubs.org/content/28/27/4184.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664033/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20660832 PubMed]
-# Guo Y, Chen Y, Hong X, Yu L, Ma J, Shi Y, Liu T, Jiang W, Zhu J, Jin J, Zou P, Wu D, Shen Z. [A phase II multicenter study to investigate R-ICE as a salvage therapy for relapsed diffuse large B-cell lymphoma]. Zhonghua Xue Ye Xue Za Zhi. 2014 Apr;35(4):314-7. Chinese. [http://zhxyxzz.yiigle.com/zhxyxzz20143504/395338.htm link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24759019 PubMed]
+#Guo Y, Chen Y, Hong X, Yu L, Ma J, Shi Y, Liu T, Jiang W, Zhu J, Jin J, Zou P, Wu D, Shen Z. [A phase II multicenter study to investigate R-ICE as a salvage therapy for relapsed diffuse large B-cell lymphoma]. Zhonghua Xue Ye Xue Za Zhi. 2014 Apr;35(4):314-7. Chinese. [http://zhxyxzz.yiigle.com/zhxyxzz20143504/395338.htm link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24759019 PubMed]
-# '''SG040-0005:''' Fayad L, Ansell SM, Advani R, Coiffier B, Stuart R, Bartlett NL, Forero-Torres A, Kuliczkowski K, Belada D, Ng E, Drachman JG. Dacetuzumab plus rituximab, ifosfamide, carboplatin and etoposide as salvage therapy for patients with diffuse large B-cell lymphoma relapsing after rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone: a randomized, double-blind, placebo-controlled phase 2b trial. Leuk Lymphoma. 2015;56(9):2569-78. Epub 2015 Feb 26. [http://www.tandfonline.com/doi/full/10.3109/10428194.2015.1007504 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25651427 PubMed]
+#'''SG040-0005:''' Fayad L, Ansell SM, Advani R, Coiffier B, Stuart R, Bartlett NL, Forero-Torres A, Kuliczkowski K, Belada D, Ng E, Drachman JG. Dacetuzumab plus rituximab, ifosfamide, carboplatin and etoposide as salvage therapy for patients with diffuse large B-cell lymphoma relapsing after rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone: a randomized, double-blind, placebo-controlled phase 2b trial. Leuk Lymphoma. 2015;56(9):2569-78. Epub 2015 Feb 26. [http://www.tandfonline.com/doi/full/10.3109/10428194.2015.1007504 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25651427 PubMed]
 ==RICER {{#subobject:28fda|Regimen=1}}==
@@ Line 3,090: / Line 3,367: @@
 ===Regimen {{#subobject:f8dffd|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4283736/ Feldman et al. 2014 (RV-DLBCL-PI-0463)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Ifosfamide (Ifex)]] 5000 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 2, '''mixed with [[Mesna (Mesnex)]]'''
@@ Line 3,105: / Line 3,383: @@
 ====Supportive medications====
 *[[Mesna (Mesnex)]] 5000 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 2, '''mixed with [[Ifosfamide (Ifex)]]'''
 *[[Aspirin]] 81 mg PO once per day from day 1 until platelets less than 50 × 10<sup>9</sup>/L
@@ Line 3,112: / Line 3,391: @@
 '''14-day cycle for 2 cycles'''
 ====Subsequent treatment====
 *Responders received a 3rd cycle with hematopoietic stem cell collection 10 to 14 days afterwards, then [[#BEAM.2C_then_auto_HSCT|BEAM with autologous hematopoietic stem cell transplant (details not described)]]
 ===References===
-# '''RV-DLBCL-PI-0463:''' Feldman T, Mato AR, Chow KF, Protomastro EA, Yannotti KM, Bhattacharyya P, Yang X, Donato ML, Rowley SD, Carini C, Valentinetti M, Smith J, Gadaleta G, Bejot C, Stives S, Timberg M, Kdiry S, Pecora AL, Beaven AW, Goy A. Addition of lenalidomide to rituximab, ifosfamide, carboplatin, etoposide (RICER) in first-relapse/primary refractory diffuse large B-cell lymphoma. Br J Haematol. 2014 Jul;166(1):77-83. Epub 2014 Mar 25. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.12846/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4283736/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24661044 PubMed]
+#'''RV-DLBCL-PI-0463:''' Feldman T, Mato AR, Chow KF, Protomastro EA, Yannotti KM, Bhattacharyya P, Yang X, Donato ML, Rowley SD, Carini C, Valentinetti M, Smith J, Gadaleta G, Bejot C, Stives S, Timberg M, Kdiry S, Pecora AL, Beaven AW, Goy A. Addition of lenalidomide to rituximab, ifosfamide, carboplatin, etoposide (RICER) in first-relapse/primary refractory diffuse large B-cell lymphoma. Br J Haematol. 2014 Jul;166(1):77-83. Epub 2014 Mar 25. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.12846/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4283736/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24661044 PubMed]
 ==R-IFE {{#subobject:19b4ea|Regimen=1}}==
@@ Line 3,125: / Line 3,406: @@
 ===Regimen {{#subobject:116aa7|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/bjh.13036/full Pardal et al. 2014 (GELTAMO-2006)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''These were patients with PET-positive disease at interim assessment.''
 ====Preceding treatment====
 *[[#R-MegaCHOP|R-MegaCHOP]] x 3
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Ifosfamide (Ifex)]] 3333 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 1 (total dose per cycle: 10,000 mg/m<sup>2</sup>)
@@ Line 3,141: / Line 3,425: @@
 ====Supportive medications====
 *[[Mesna (Mesnex)]] given after R-IFE; details not supplied in manuscript
 *[[Pegfilgrastim (Neulasta)]] given after each cycle
@@ Line 3,146: / Line 3,431: @@
 '''2 cycles (duration not specified)'''
 ====Subsequent treatment====
 *Responders: [[#BEAM.2C_then_auto_HSCT|BEAM with autologous hematopoietic stem cell transplant]]
 ===References===
-# '''GELTAMO-2006:''' Pardal E, Coronado M, Martín A, Grande C, Marín-Niebla A, Panizo C, Bello JL, Conde E, Hernández MT, Arranz R, Bargay J, González-Barca E, Pérez-Ceballos E, Montes-Moreno S, Caballero MD. Intensification treatment based on early FDG-PET in patients with high-risk diffuse large B-cell lymphoma: a phase II GELTAMO trial. Br J Haematol. 2014 Nov;167(3):327-36. Epub 2014 Jul 28. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13036/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25066542 PubMed]
+#'''GELTAMO-2006:''' Pardal E, Coronado M, Martín A, Grande C, Marín-Niebla A, Panizo C, Bello JL, Conde E, Hernández MT, Arranz R, Bargay J, González-Barca E, Pérez-Ceballos E, Montes-Moreno S, Caballero MD. Intensification treatment based on early FDG-PET in patients with high-risk diffuse large B-cell lymphoma: a phase II GELTAMO trial. Br J Haematol. 2014 Nov;167(3):327-36. Epub 2014 Jul 28. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13036/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25066542 PubMed]
 ==R-NIMP {{#subobject:fb6d8|Regimen=1}}==
@@ Line 3,160: / Line 3,447: @@
 ===Regimen {{#subobject:8fecee|Variant=1}}===
 {| class="wikitable" style="width: 75%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 33%" |Study
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
+! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/bjh.12379/full Gyan et al. 2013]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |68% (95%CI: 53–79)
 |-
@@ Line 3,171: / Line 3,458: @@
 ''BSA was capped at 2 for all dose calculations.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV once per day on days 1 & 15
@@ Line 3,178: / Line 3,466: @@
 ====Supportive medications====
 *[[Mesna (Mesnex)]] given with [[Ifosfamide (Ifex)]] "at the same dose"; schedule not specified in the paper
 *Recommended: [[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 7
@@ Line 3,184: / Line 3,473: @@
 '''28-day cycle for 3 cycles'''
 ====Subsequent treatment====
 *Responders were recommended to undergo 3 additional cycles of R-NIMP (if transplant ineligible) or high-dose chemotherapy with autologous hematopoietic stem cell transplant (regimen not specified).
 ===References===
-# Gyan E, Damotte D, Courby S, Sénécal D, Quittet P, Schmidt-Tanguy A, Banos A, Le Gouill S, Lamy T, Fontan J, Maisonneuve H, Alexis M, Dreyfus F, Tournilhac O, Laribi K, Solal-Céligny P, Arakelyan N, Cartron G, Gressin R; GOELAMS Group. High response rate and acceptable toxicity of a combination of rituximab, vinorelbine, ifosfamide, mitoxantrone and prednisone for the treatment of diffuse large B-cell lymphoma in first relapse: results of the R-NIMP GOELAMS study. Br J Haematol. 2013 Jul;162(2):240-9. Epub 2013 May 21. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.12379/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23692641 PubMed]
+#Gyan E, Damotte D, Courby S, Sénécal D, Quittet P, Schmidt-Tanguy A, Banos A, Le Gouill S, Lamy T, Fontan J, Maisonneuve H, Alexis M, Dreyfus F, Tournilhac O, Laribi K, Solal-Céligny P, Arakelyan N, Cartron G, Gressin R; GOELAMS Group. High response rate and acceptable toxicity of a combination of rituximab, vinorelbine, ifosfamide, mitoxantrone and prednisone for the treatment of diffuse large B-cell lymphoma in first relapse: results of the R-NIMP GOELAMS study. Br J Haematol. 2013 Jul;162(2):240-9. Epub 2013 May 21. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.12379/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23692641 PubMed]
 =Consolidation after salvage therapy=
@@ Line 3,199: / Line 3,490: @@
 ===Regimen {{#subobject:61a3cd|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://www.bloodjournal.org/content/77/7/1587.long Philip et al. 1991 (Parma)]
@@ Line 3,210: / Line 3,501: @@
 |-
 |[https://www.nejm.org/doi/full/10.1056/NEJM199512073332305 Philip et al. 1995 (PARMA)]
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#1a9851" |Phase III (E-esc)
 |[[#DHAP|DHAP]] x 4
-|style="background-color:#91cf60"|Seems to have superior OS
+| style="background-color:#91cf60" |Seems to have superior OS
 |-
 |}
@@ Line 3,219: / Line 3,510: @@
 {{#lst:Autologous HSCT conditioning regimens|728b1c}}
 ===References===
-# Philip T, Chauvin F, Armitage J, Bron D, Hagenbeek A, Biron P, Spitzer G, Velasquez W, Weisenburger DD, Fernandez-Ranada J, Somers R, Rizzoli V, Harousseau JL, Sotto JJ, Cahn JY, Guilhot F, Biggs J, Sonneveld P, Misset JL, Manna A, Jagannath S, Guglielmi C, Chevreau C, Delmer A, Santini G, Coiffier B. Parma international protocol: pilot study of DHAP followed by involved-field radiotherapy and BEAC with autologous bone marrow transplantation. Blood. 1991 Apr 1;77(7):1587-92. [http://www.bloodjournal.org/content/77/7/1587.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/2009374 PubMed]
-# '''PARMA:''' Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, Coiffier B, Biron P, Mandelli F, Chauvin F. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med. 1995 Dec 7;333(23):1540-5. [https://www.nejm.org/doi/full/10.1056/NEJM199512073332305 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7477169 PubMed]
+#Philip T, Chauvin F, Armitage J, Bron D, Hagenbeek A, Biron P, Spitzer G, Velasquez W, Weisenburger DD, Fernandez-Ranada J, Somers R, Rizzoli V, Harousseau JL, Sotto JJ, Cahn JY, Guilhot F, Biggs J, Sonneveld P, Misset JL, Manna A, Jagannath S, Guglielmi C, Chevreau C, Delmer A, Santini G, Coiffier B. Parma international protocol: pilot study of DHAP followed by involved-field radiotherapy and BEAC with autologous bone marrow transplantation. Blood. 1991 Apr 1;77(7):1587-92. [http://www.bloodjournal.org/content/77/7/1587.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/2009374 PubMed]
+#'''PARMA:''' Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, Coiffier B, Biron P, Mandelli F, Chauvin F. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med. 1995 Dec 7;333(23):1540-5. [https://www.nejm.org/doi/full/10.1056/NEJM199512073332305 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7477169 PubMed]
 ==BEAM, then allo HSCT {{#subobject:bda306|Regimen=1}}==
@@ Line 3,230: / Line 3,522: @@
 ===Regimen {{#subobject:a8d4a|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://annonc.oxfordjournals.org/content/10/5/527.long Przepiorka et al. 1999]
@@ Line 3,239: / Line 3,531: @@
 {{#lst:Allogeneic HSCT|a8d4a}}
 ====Immunotherapy====
 *[[Allogeneic stem cells]]
 '''Stem cells transfused on day 0'''
 ===References===
-# Przepiorka D, van Besien K, Khouri I, Hagemeister F, Samuels B, Folloder J, Ueno NT, Molldrem J, Mehra R, Körbling M, Giralt S, Gajewski J, Donato M, Cleary K, Claxton D, Braunschweig I, Andersson B, Anderlini P, Champlin R. Carmustine, etoposide, cytarabine and melphalan as a preparative regimen for allogeneic transplantation for high-risk malignant lymphoma. Ann Oncol. 1999 May;10(5):527-32. [http://annonc.oxfordjournals.org/content/10/5/527.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10416001 PubMed]
+#Przepiorka D, van Besien K, Khouri I, Hagemeister F, Samuels B, Folloder J, Ueno NT, Molldrem J, Mehra R, Körbling M, Giralt S, Gajewski J, Donato M, Cleary K, Claxton D, Braunschweig I, Andersson B, Anderlini P, Champlin R. Carmustine, etoposide, cytarabine and melphalan as a preparative regimen for allogeneic transplantation for high-risk malignant lymphoma. Ann Oncol. 1999 May;10(5):527-32. [http://annonc.oxfordjournals.org/content/10/5/527.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10416001 PubMed]
 ==BEAM, then auto HSCT {{#subobject:0304c6|Regimen=1}}==
@@ Line 3,253: / Line 3,548: @@
 ===Regimen variant #1 {{#subobject:445dc0|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1002/cncr.27418/full Shimoni et al. 2012 (SHEBA-07-4466-AN-CTIL)]
@@ Line 3,264: / Line 3,559: @@
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/bjh.13036/full Pardal et al. 2014 (GELTAMO-2006)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 | style="background-color:#d3d3d3" |
 | style="background-color:#d3d3d3" |
 |-
 |[https://ascopubs.org/doi/full/10.1200/JCO.2016.69.0198 van Imhoff et al. 2016 (ORCHARRD)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 | style="background-color:#d3d3d3" |
 | style="background-color:#d3d3d3" |
@@ Line 3,275: / Line 3,570: @@
 |}
 ====Preceding treatment====
 *GELTAMO-2006: [[#R-MegaCHOP|R-MegaCHOP]] x 3, then [[#R-IFE_2|R-IFE]] x 2
 *ORCHARRD: [[#O-DHAP|O-DHAP]] x 3 versus [[#R-DHAP|R-DHAP]] x 3
@@ Line 3,282: / Line 3,578: @@
 ===Regimen variant #2 {{#subobject:445dc0|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://www.bloodjournal.org/content/111/2/537.long Vellenga et al. 2008 (HOVON-44)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664033/ Gisselbrecht et al. 2010 (CORAL)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |}
 ====Preceding treatment====
 *HOVON-44: DHAP/VIM versus [[#R-DHAP.2FR-VIM|R-DHAP/R-VIM]]
 *CORAL: [[#R-ICE|R-ICE]] x 3 versus [[#R-DHAP|R-DHAP]] x 3
@@ Line 3,299: / Line 3,596: @@
 ====Subsequent treatment====
 *CORAL: [[#Rituximab_monotherapy_2|Rituximab maintenance]] versus [[#Observation_2|observation]]
 ===Regimen variant #3, 300/100q12/200/140 {{#subobject:76416d|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.nejm.org/doi/full/10.1056/NEJM198706113162401 Philip et al. 1987]
-|style="background-color:#91cf61"|Non-randomized
+| style="background-color:#91cf61" |Non-randomized
 |-
 |}
 {{#lst:Autologous HSCT|76416d}}
 ===References===
-# Philip T, Armitage JO, Spitzer G, Chauvin F, Jagannath S, Cahn JY, Colombat P, Goldstone AH, Gorin NC, Flesh M, Laporte JP, Maraninchi D, Pico J, Bosly A, Anderson C, Schots R, Biron P, Cabanillas F, Dicke K. High-dose therapy and autologous bone marrow transplantation after failure of conventional chemotherapy in adults with intermediate-grade or high-grade non-Hodgkin's lymphoma. N Engl J Med. 1987 Jun 11;316(24):1493-8. [https://www.nejm.org/doi/full/10.1056/NEJM198706113162401 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/3295541 PubMed]
-# '''HOVON-44:''' Vellenga E, van Putten WL, van 't Veer MB, Zijlstra JM, Fibbe WE, van Oers MH, Verdonck LF, Wijermans PW, van Imhoff GW, Lugtenburg PJ, Huijgens PC. Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20+ NHL: a prospective randomized HOVON trial. Blood. 2008 Jan 15;111(2):537-43. [http://www.bloodjournal.org/content/111/2/537.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17971487 PubMed]
+#Philip T, Armitage JO, Spitzer G, Chauvin F, Jagannath S, Cahn JY, Colombat P, Goldstone AH, Gorin NC, Flesh M, Laporte JP, Maraninchi D, Pico J, Bosly A, Anderson C, Schots R, Biron P, Cabanillas F, Dicke K. High-dose therapy and autologous bone marrow transplantation after failure of conventional chemotherapy in adults with intermediate-grade or high-grade non-Hodgkin's lymphoma. N Engl J Med. 1987 Jun 11;316(24):1493-8. [https://www.nejm.org/doi/full/10.1056/NEJM198706113162401 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/3295541 PubMed]
+#'''HOVON-44:''' Vellenga E, van Putten WL, van 't Veer MB, Zijlstra JM, Fibbe WE, van Oers MH, Verdonck LF, Wijermans PW, van Imhoff GW, Lugtenburg PJ, Huijgens PC. Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20+ NHL: a prospective randomized HOVON trial. Blood. 2008 Jan 15;111(2):537-43. [http://www.bloodjournal.org/content/111/2/537.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17971487 PubMed]
 <!--
 Presented at the 45th Annual Meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL, and at the 51st Annual Meeting of the American Society of Hematology, December 5-8, 2009, New Orleans, LA. -->
-# '''CORAL:''' Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Brière J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. Epub 2010 Jul 26. Erratum in: J Clin Oncol. 2012 May 20;30(15):1896. [http://jco.ascopubs.org/content/28/27/4184.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664033/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20660832 PubMed]
+#'''CORAL:''' Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Brière J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. Epub 2010 Jul 26. Erratum in: J Clin Oncol. 2012 May 20;30(15):1896. [http://jco.ascopubs.org/content/28/27/4184.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664033/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20660832 PubMed]
-# '''SHEBA-07-4466-AN-CTIL:''' Shimoni A, Avivi I, Rowe JM, Yeshurun M, Levi I, Or R, Patachenko P, Avigdor A, Zwas T, Nagler A. A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma. Cancer. 2012 Oct 1;118(19):4706-14. Epub 2012 Jan 17. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.27418/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22252613 PubMed]
+#'''SHEBA-07-4466-AN-CTIL:''' Shimoni A, Avivi I, Rowe JM, Yeshurun M, Levi I, Or R, Patachenko P, Avigdor A, Zwas T, Nagler A. A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma. Cancer. 2012 Oct 1;118(19):4706-14. Epub 2012 Jan 17. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.27418/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22252613 PubMed]
-# '''GELTAMO-2006:''' Pardal E, Coronado M, Martín A, Grande C, Marín-Niebla A, Panizo C, Bello JL, Conde E, Hernández MT, Arranz R, Bargay J, González-Barca E, Pérez-Ceballos E, Montes-Moreno S, Caballero MD. Intensification treatment based on early FDG-PET in patients with high-risk diffuse large B-cell lymphoma: a phase II GELTAMO trial. Br J Haematol. 2014 Nov;167(3):327-36. Epub 2014 Jul 28. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13036/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25066542 PubMed]
+#'''GELTAMO-2006:''' Pardal E, Coronado M, Martín A, Grande C, Marín-Niebla A, Panizo C, Bello JL, Conde E, Hernández MT, Arranz R, Bargay J, González-Barca E, Pérez-Ceballos E, Montes-Moreno S, Caballero MD. Intensification treatment based on early FDG-PET in patients with high-risk diffuse large B-cell lymphoma: a phase II GELTAMO trial. Br J Haematol. 2014 Nov;167(3):327-36. Epub 2014 Jul 28. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13036/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25066542 PubMed]
-# '''ORCHARRD:''' van Imhoff GW, McMillan A, Matasar MJ, Radford J, Ardeshna KM, Kuliczkowski K, Kim W, Hong X, Goerloev JS, Davies A, Barrigón MD, Ogura M, Leppä S, Fennessy M, Liao Q, van der Holt B, Lisby S, Hagenbeek A. Ofatumumab versus rituximab salvage chemoimmunotherapy in relapsed or refractory diffuse large B-cell lymphoma: the ORCHARRD study. J Clin Oncol. 2017 Feb 10;35(5):544-51. Epub 2016 Dec 28. [https://ascopubs.org/doi/full/10.1200/JCO.2016.69.0198 link to original article] [https://ascopubs.org/doi/suppl/10.1200/JCO.2016.69.0198/suppl_file/ds_2016.690198.pdf link to data supplement] '''verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/28029326 PubMed]
+#'''ORCHARRD:''' van Imhoff GW, McMillan A, Matasar MJ, Radford J, Ardeshna KM, Kuliczkowski K, Kim W, Hong X, Goerloev JS, Davies A, Barrigón MD, Ogura M, Leppä S, Fennessy M, Liao Q, van der Holt B, Lisby S, Hagenbeek A. Ofatumumab versus rituximab salvage chemoimmunotherapy in relapsed or refractory diffuse large B-cell lymphoma: the ORCHARRD study. J Clin Oncol. 2017 Feb 10;35(5):544-51. Epub 2016 Dec 28. [https://ascopubs.org/doi/full/10.1200/JCO.2016.69.0198 link to original article] [https://ascopubs.org/doi/suppl/10.1200/JCO.2016.69.0198/suppl_file/ds_2016.690198.pdf link to data supplement] '''verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/28029326 PubMed]
 ==BeEAM, then auto HSCT {{#subobject:dee72f|Regimen=1}}==
@@ Line 3,329: / Line 3,628: @@
 ===Regimen {{#subobject:81ff2e|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://www.bloodjournal.org/content/118/12/3419.long Visani et al. 2011]
@@ Line 3,338: / Line 3,637: @@
 {{#lst:Autologous HSCT|81ff2e}}
 ===References===
-# Visani G, Malerba L, Stefani PM, Capria S, Galieni P, Gaudio F, Specchia G, Meloni G, Gherlinzoni F, Giardini C, Falcioni S, Cuberli F, Gobbi M, Sarina B, Santoro A, Ferrara F, Rocchi M, Ocio EM, Caballero MD, Isidori A. BeEAM (bendamustine, etoposide, cytarabine, melphalan) before autologous stem cell transplantation is safe and effective for resistant/relapsed lymphoma patients. Blood. 2011 Sep 22;118(12):3419-25. Epub 2011 Aug 3. [http://www.bloodjournal.org/content/118/12/3419.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21816830 PubMed]
+#Visani G, Malerba L, Stefani PM, Capria S, Galieni P, Gaudio F, Specchia G, Meloni G, Gherlinzoni F, Giardini C, Falcioni S, Cuberli F, Gobbi M, Sarina B, Santoro A, Ferrara F, Rocchi M, Ocio EM, Caballero MD, Isidori A. BeEAM (bendamustine, etoposide, cytarabine, melphalan) before autologous stem cell transplantation is safe and effective for resistant/relapsed lymphoma patients. Blood. 2011 Sep 22;118(12):3419-25. Epub 2011 Aug 3. [http://www.bloodjournal.org/content/118/12/3419.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21816830 PubMed]
 ==CBV, then auto HSCT {{#subobject:935235|Regimen=1}}==
@@ Line 3,348: / Line 3,648: @@
 ===Regimen {{#subobject:35a696|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://jco.ascopubs.org/content/16/1/48.long Stiff et al. 1998]
@@ Line 3,357: / Line 3,657: @@
 {{#lst:Autologous HSCT|35a696}}
 ===References===
-# Stiff PJ, Dahlberg S, Forman SJ, McCall AR, Horning SJ, Nademanee AP, Blume KG, LeBlanc M, Fisher RI. Autologous bone marrow transplantation for patients with relapsed or refractory diffuse aggressive non-Hodgkin's lymphoma: value of augmented preparative regimens--a Southwest Oncology Group trial. J Clin Oncol. 1998 Jan;16(1):48-55. [http://jco.ascopubs.org/content/16/1/48.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9440722 PubMed]
+#Stiff PJ, Dahlberg S, Forman SJ, McCall AR, Horning SJ, Nademanee AP, Blume KG, LeBlanc M, Fisher RI. Autologous bone marrow transplantation for patients with relapsed or refractory diffuse aggressive non-Hodgkin's lymphoma: value of augmented preparative regimens--a Southwest Oncology Group trial. J Clin Oncol. 1998 Jan;16(1):48-55. [http://jco.ascopubs.org/content/16/1/48.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9440722 PubMed]
 ==Cyclophosphamide & TBI, then auto HSCT {{#subobject:0a4915|Regimen=1}}==
@@ Line 3,367: / Line 3,668: @@
 ===Regimen {{#subobject:a2b2d3|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.nejm.org/doi/full/10.1056/NEJM198406143102403 Phillips et al. 1984]
@@ Line 3,376: / Line 3,677: @@
 {{#lst:Autologous HSCT|a2b2d3}}
 ===References===
-# Phillips GL, Herzig RH, Lazarus HM, Fay JW, Wolff SN, Mill WB, Lin H, Thomas PR, Glasgow GP, Shina DC, Herzig GP. Treatment of resistant malignant lymphoma with cyclophosphamide, total body irradiation, and transplantation of cryopreserved autologous marrow. N Engl J Med. 1984 Jun 14;310(24):1557-61. [https://www.nejm.org/doi/full/10.1056/NEJM198406143102403 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6374452 PubMed]
+#Phillips GL, Herzig RH, Lazarus HM, Fay JW, Wolff SN, Mill WB, Lin H, Thomas PR, Glasgow GP, Shina DC, Herzig GP. Treatment of resistant malignant lymphoma with cyclophosphamide, total body irradiation, and transplantation of cryopreserved autologous marrow. N Engl J Med. 1984 Jun 14;310(24):1557-61. [https://www.nejm.org/doi/full/10.1056/NEJM198406143102403 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6374452 PubMed]
 ==FEAM, then auto HSCT {{#subobject:0aac6f|Regimen=1}}==
@@ Line 3,386: / Line 3,688: @@
 ===Regimen {{#subobject:74d43c|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.nature.com/bmt/journal/v45/n7/full/bmt2009318a.html Musso et al. 2009]
@@ Line 3,395: / Line 3,697: @@
 {{#lst:Autologous HSCT|74d43c}}
 ===References===
-# Musso M, Scalone R, Marcacci G, Lanza F, Di Renzo N, Cascavilla N, Di Bartolomeo P, Crescimanno A, Perrone T, Pinto A. Fotemustine plus etoposide, cytarabine and melphalan (FEAM) as a new conditioning regimen for lymphoma patients undergoing auto-SCT: a multicenter feasibility study. Bone Marrow Transplant. 2010 Jul;45(7):1147-53. Epub 2009 Nov 9. [https://www.nature.com/bmt/journal/v45/n7/full/bmt2009318a.html link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19898504 PubMed]
+#Musso M, Scalone R, Marcacci G, Lanza F, Di Renzo N, Cascavilla N, Di Bartolomeo P, Crescimanno A, Perrone T, Pinto A. Fotemustine plus etoposide, cytarabine and melphalan (FEAM) as a new conditioning regimen for lymphoma patients undergoing auto-SCT: a multicenter feasibility study. Bone Marrow Transplant. 2010 Jul;45(7):1147-53. Epub 2009 Nov 9. [https://www.nature.com/bmt/journal/v45/n7/full/bmt2009318a.html link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19898504 PubMed]
 ==FluBuCy, then allo HSCT {{#subobject:84acb0|Regimen=1}}==
@@ Line 3,405: / Line 3,708: @@
 ===Regimen {{#subobject:bfe434|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70161-5/fulltext Glass et al. 2014 (DSHNHL R3)]
@@ Line 3,414: / Line 3,717: @@
 {{#lst:Allogeneic HSCT|bfe434}}
 ====Immunotherapy====
 *[[Allogeneic stem cells]]
 '''Stem cells transfused on day 0'''
 ===References===
 <!-- # Glass B, rabbits Kamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M Silling G, Wilhelm C, Zeis M, Görlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N. High-dose chemotherapy Followed by allogeneic stem cell transplantation in relapsed and refractory high-risk aggressive non-Hodgkin's lymphoma: Results of a prospective study of the German high-grade non-Hodgkin's lymphoma study group. J Clin Oncol 30, 2012 (suppl; abstr 8004) -->
-# '''DSHNHL R3:''' Glass B, Hasenkamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M, Silling G, Wilhelm C, Zeis M, Görlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N; German High-Grade Lymphoma Study Group. Rituximab after lymphoma-directed conditioning and allogeneic stem-cell transplantation for relapsed and refractory aggressive non-Hodgkin lymphoma (DSHNHL R3): an open-label, randomised, phase 2 trial. Lancet Oncol. 2014 Jun;15(7):757-66. Epub 2014 May 11. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70161-5/fulltext link to original article] [http://www.dshnhl.org/app/download/9495510598/Studienprotokoll+DSHNHL+alloFBC+final+vollst.pdf link to original protocol (in German)] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24827808 PubMed]
+#'''DSHNHL R3:''' Glass B, Hasenkamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M, Silling G, Wilhelm C, Zeis M, Görlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N; German High-Grade Lymphoma Study Group. Rituximab after lymphoma-directed conditioning and allogeneic stem-cell transplantation for relapsed and refractory aggressive non-Hodgkin lymphoma (DSHNHL R3): an open-label, randomised, phase 2 trial. Lancet Oncol. 2014 Jun;15(7):757-66. Epub 2014 May 11. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70161-5/fulltext link to original article] [http://www.dshnhl.org/app/download/9495510598/Studienprotokoll+DSHNHL+alloFBC+final+vollst.pdf link to original protocol (in German)] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24827808 PubMed]
 ==Fludarabine, Busulfan, ATG, Ibritumomab tiuxetan, then allo HSCT {{#subobject:68bee2|Regimen=1}}==
@@ Line 3,427: / Line 3,733: @@
 ===Regimen {{#subobject:822e5a|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://annonc.oxfordjournals.org/content/26/1/193.full Bouabdallah et al. 2015 (ZEVALLO)]
@@ Line 3,436: / Line 3,742: @@
 {{#lst:Allogeneic HSCT|822e5a}}
 ====Immunotherapy====
 *[[Allogeneic stem cells]]
 '''Stem cells transfused on day 0'''
 ===References===
-# '''ZEVALLO:''' Bouabdallah K, Furst S, Asselineau J, Chevalier P, Tournilhac O, Ceballos P, Vigouroux S, Tabrizi R, Doussau A, Bouabdallah R, Mohty M, Le Gouill S, Blaise D, Milpied N. 90Y-ibritumomab tiuxetan, fludarabine, busulfan and antithymocyte globulin reduced-intensity allogeneic transplant conditioning for patients with advanced and high-risk B-cell lymphomas. Ann Oncol. 2015 Jan;26(1):193-8. Epub 2014 Oct 30. [http://annonc.oxfordjournals.org/content/26/1/193.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25361987 PubMed]
+#'''ZEVALLO:''' Bouabdallah K, Furst S, Asselineau J, Chevalier P, Tournilhac O, Ceballos P, Vigouroux S, Tabrizi R, Doussau A, Bouabdallah R, Mohty M, Le Gouill S, Blaise D, Milpied N. 90Y-ibritumomab tiuxetan, fludarabine, busulfan and antithymocyte globulin reduced-intensity allogeneic transplant conditioning for patients with advanced and high-risk B-cell lymphomas. Ann Oncol. 2015 Jan;26(1):193-8. Epub 2014 Oct 30. [http://annonc.oxfordjournals.org/content/26/1/193.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25361987 PubMed]
 ==LEED, then auto HSCT {{#subobject:bf49e4|Regimen=1}}==
@@ Line 3,449: / Line 3,758: @@
 ===Regimen {{#subobject:a8ec2f|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://ascopubs.org/doi/full/10.1200/JCO.2016.69.0198 van Imhoff et al. 2016 (ORCHARRD)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |}
 ====Preceding treatment====
 *[[#O-DHAP|O-DHAP]] x 3 versus [[#R-DHAP|R-DHAP]] x 3
 {{#lst:Autologous HSCT conditioning regimens|47e3df}}
@@ Line 3,462: / Line 3,772: @@
 ===References===
-# '''ORCHARRD:''' van Imhoff GW, McMillan A, Matasar MJ, Radford J, Ardeshna KM, Kuliczkowski K, Kim W, Hong X, Goerloev JS, Davies A, Barrigón MD, Ogura M, Leppä S, Fennessy M, Liao Q, van der Holt B, Lisby S, Hagenbeek A. Ofatumumab versus rituximab salvage chemoimmunotherapy in relapsed or refractory diffuse large B-cell lymphoma: the ORCHARRD study. J Clin Oncol. 2017 Feb 10;35(5):544-51. Epub 2016 Dec 28. [https://ascopubs.org/doi/full/10.1200/JCO.2016.69.0198 link to original article] [https://ascopubs.org/doi/suppl/10.1200/JCO.2016.69.0198/suppl_file/ds_2016.690198.pdf link to data supplement] '''verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/28029326 PubMed]
+#'''ORCHARRD:''' van Imhoff GW, McMillan A, Matasar MJ, Radford J, Ardeshna KM, Kuliczkowski K, Kim W, Hong X, Goerloev JS, Davies A, Barrigón MD, Ogura M, Leppä S, Fennessy M, Liao Q, van der Holt B, Lisby S, Hagenbeek A. Ofatumumab versus rituximab salvage chemoimmunotherapy in relapsed or refractory diffuse large B-cell lymphoma: the ORCHARRD study. J Clin Oncol. 2017 Feb 10;35(5):544-51. Epub 2016 Dec 28. [https://ascopubs.org/doi/full/10.1200/JCO.2016.69.0198 link to original article] [https://ascopubs.org/doi/suppl/10.1200/JCO.2016.69.0198/suppl_file/ds_2016.690198.pdf link to data supplement] '''verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/28029326 PubMed]
 ==R-BEAM, then auto HSCT {{#subobject:8b88db|Regimen=1}}==
@@ Line 3,472: / Line 3,783: @@
 ===Regimen variant #1, 750/300/800/800/140 {{#subobject:9131e1|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://ascopubs.org/doi/full/10.1200/JCO.2012.45.9453 Vose et al. 2013 (BMT CTN 0401)]
@@ Line 3,488: / Line 3,799: @@
 ===Regimen variant #2, 750/300/1600/3200/140 {{#subobject:77f5a0|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/bjh.13234/full Kirschey et al. 2014 (Mz-135)]
@@ Line 3,497: / Line 3,808: @@
 ''A minimum number of 2 × 10<sup>6</sup>/kg bw CD34-positive cells were required to proceed.''
 ====Preceding treatment====
 *[[#R-DexaBEAM|R-DexaBEAM]] x 2
 {{#lst:Autologous HSCT conditioning regimens|77f5a0}}
 ===References===
-# '''BMT CTN 0401:''' Vose JM, Carter S, Burns LJ, Ayala E, Press OW, Moskowitz CH, Stadtmauer EA, Mineshi S, Ambinder R, Fenske T, Horowitz M, Fisher R, Tomblyn M. Phase III randomized study of rituximab/carmustine, etoposide, cytarabine, and melphalan (BEAM) compared with iodine-131 tositumomab/BEAM with autologous hematopoietic cell transplantation for relapsed diffuse large B-cell lymphoma: results from the BMT CTN 0401 trial. J Clin Oncol. 2013 May 1;31(13):1662-8. Epub 2013 Mar 11. [https://ascopubs.org/doi/full/10.1200/JCO.2012.45.9453 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3635682/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23478060 PubMed]
-# '''Mz-135:''' Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13234/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25546611 PubMed]
+#'''BMT CTN 0401:''' Vose JM, Carter S, Burns LJ, Ayala E, Press OW, Moskowitz CH, Stadtmauer EA, Mineshi S, Ambinder R, Fenske T, Horowitz M, Fisher R, Tomblyn M. Phase III randomized study of rituximab/carmustine, etoposide, cytarabine, and melphalan (BEAM) compared with iodine-131 tositumomab/BEAM with autologous hematopoietic cell transplantation for relapsed diffuse large B-cell lymphoma: results from the BMT CTN 0401 trial. J Clin Oncol. 2013 May 1;31(13):1662-8. Epub 2013 Mar 11. [https://ascopubs.org/doi/full/10.1200/JCO.2012.45.9453 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3635682/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23478060 PubMed]
+#'''Mz-135:''' Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13234/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25546611 PubMed]
 ==R-TBI/Cy, then auto HSCT {{#subobject:38a16a|Regimen=1}}==
@@ Line 3,511: / Line 3,824: @@
 ===Regimen {{#subobject:1b28ce|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/bjh.13234/full Kirschey et al. 2014 (Mz-135)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Preceding treatment====
 *[[#R-DexaBEAM|R-DexaBEAM]] x 2
 {{#lst:Autologous HSCT conditioning regimens|785614}}
 '''Stem cells reinfused on day 0'''
 ===References===
-# '''Mz-135:''' Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13234/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25546611 PubMed]
+#'''Mz-135:''' Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13234/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25546611 PubMed]
 ==Z-BEAM, then auto HSCT {{#subobject:a6ae5d|Regimen=1}}==
@@ Line 3,533: / Line 3,848: @@
 ===Regimen {{#subobject:df0b80|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://www.exphem.org/article/S0301-472X(07)00050-1/fulltext Shimoni et al. 2007]
@@ Line 3,558: / Line 3,873: @@
 ===References===
-# Shimoni A, Zwas ST, Oksman Y, Hardan I, Shem-Tov N, Yerushalmi R, Avigdor A, Ben-Bassat I, Nagler A. Yttrium-90-ibritumomab tiuxetan (Zevalin) combined with high-dose BEAM chemotherapy and autologous stem cell transplantation for chemo-refractory aggressive non-Hodgkin's lymphoma. Exp Hematol. 2007 Apr;35(4):534-40. [http://www.exphem.org/article/S0301-472X(07)00050-1/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17379063 PubMed]
-# '''SHEBA-07-4466-AN-CTIL:''' Shimoni A, Avivi I, Rowe JM, Yeshurun M, Levi I, Or R, Patachenko P, Avigdor A, Zwas T, Nagler A. A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma. Cancer. 2012 Oct 1;118(19):4706-14. Epub 2012 Jan 17. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.27418/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22252613 PubMed]
+#Shimoni A, Zwas ST, Oksman Y, Hardan I, Shem-Tov N, Yerushalmi R, Avigdor A, Ben-Bassat I, Nagler A. Yttrium-90-ibritumomab tiuxetan (Zevalin) combined with high-dose BEAM chemotherapy and autologous stem cell transplantation for chemo-refractory aggressive non-Hodgkin's lymphoma. Exp Hematol. 2007 Apr;35(4):534-40. [http://www.exphem.org/article/S0301-472X(07)00050-1/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17379063 PubMed]
-# '''GELTAMO Z-BEAM LDCGB:''' Briones J, Novelli S, García-Marco JA, Tomás JF, Bernal T, Grande C, Canales MA, Torres A, Moraleda JM, Panizo C, Jarque I, Palmero F, Hernsández M, González-Barca E, López D, Caballero D. Autologous stem cell transplantation after conditioning with Yttrium-90 ibritumomab tiuxetan plus beam in refractory non-Hodgkin diffuse large B-cell lymphoma: results of a prospective, multicenter, phase II clinical trial. Haematologica. 2014 Mar;99(3):505-10. Epub 2013 Oct 25. [http://www.haematologica.org/content/99/3/505.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943314/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24162789 PubMed]
+#'''SHEBA-07-4466-AN-CTIL:''' Shimoni A, Avivi I, Rowe JM, Yeshurun M, Levi I, Or R, Patachenko P, Avigdor A, Zwas T, Nagler A. A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma. Cancer. 2012 Oct 1;118(19):4706-14. Epub 2012 Jan 17. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.27418/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22252613 PubMed]
+#'''GELTAMO Z-BEAM LDCGB:''' Briones J, Novelli S, García-Marco JA, Tomás JF, Bernal T, Grande C, Canales MA, Torres A, Moraleda JM, Panizo C, Jarque I, Palmero F, Hernsández M, González-Barca E, López D, Caballero D. Autologous stem cell transplantation after conditioning with Yttrium-90 ibritumomab tiuxetan plus beam in refractory non-Hodgkin diffuse large B-cell lymphoma: results of a prospective, multicenter, phase II clinical trial. Haematologica. 2014 Mar;99(3):505-10. Epub 2013 Oct 25. [http://www.haematologica.org/content/99/3/505.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943314/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24162789 PubMed]
 =Maintenance after salvage therapy=
@@ Line 3,570: / Line 3,886: @@
 ===Regimen variant #1, 25 mg 21/28, indefinite {{#subobject:ac6517|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(17)30016-9/fulltext Ferreri et al. 2017]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Preceding treatment====
 *Rituximab-containing salvage chemotherapy
 ====Chemotherapy====
 *[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
@@ Line 3,586: / Line 3,905: @@
 ===Regimen variant #2, 25 mg 21/28 for 12 months {{#subobject:baf27c|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4283736/ Feldman et al. 2014 (RV-DLBCL-PI-0463)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Preceding treatment====
 *[[#BEAM.2C_then_auto_HSCT|BEAM with autologous hematopoietic stem cell transplant (details not described)]]
 ====Chemotherapy====
 *[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
@@ Line 3,601: / Line 3,923: @@
 ===References===
-# '''RV-DLBCL-PI-0463:''' Feldman T, Mato AR, Chow KF, Protomastro EA, Yannotti KM, Bhattacharyya P, Yang X, Donato ML, Rowley SD, Carini C, Valentinetti M, Smith J, Gadaleta G, Bejot C, Stives S, Timberg M, Kdiry S, Pecora AL, Beaven AW, Goy A. Addition of lenalidomide to rituximab, ifosfamide, carboplatin, etoposide (RICER) in first-relapse/primary refractory diffuse large B-cell lymphoma. Br J Haematol. 2014 Jul;166(1):77-83. Epub 2014 Mar 25. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.12846/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4283736/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24661044 PubMed]
-# Ferreri AJ, Sassone M, Zaja F, Re A, Spina M, di Rocco A, Fabbri A, Stelitano C, Frezzato M, Rusconi C, Zambello R, Couto S, Ren Y, Arcari A, Bertoldero G, Nonis A, Scarfò L, Calimeri T, Cecchetti C, Chiozzotto M, Govi S, Ponzoni M. Lenalidomide maintenance in patients with relapsed diffuse large B-cell lymphoma who are not eligible for autologous stem cell transplantation: an open label, single-arm, multicentre phase 2 trial. Lancet Haematol. 2017 Mar;4(3):e137-e146. Epub 2017 Feb 17. [https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(17)30016-9/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28219694 PubMed]
+#'''RV-DLBCL-PI-0463:''' Feldman T, Mato AR, Chow KF, Protomastro EA, Yannotti KM, Bhattacharyya P, Yang X, Donato ML, Rowley SD, Carini C, Valentinetti M, Smith J, Gadaleta G, Bejot C, Stives S, Timberg M, Kdiry S, Pecora AL, Beaven AW, Goy A. Addition of lenalidomide to rituximab, ifosfamide, carboplatin, etoposide (RICER) in first-relapse/primary refractory diffuse large B-cell lymphoma. Br J Haematol. 2014 Jul;166(1):77-83. Epub 2014 Mar 25. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.12846/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4283736/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24661044 PubMed]
+#Ferreri AJ, Sassone M, Zaja F, Re A, Spina M, di Rocco A, Fabbri A, Stelitano C, Frezzato M, Rusconi C, Zambello R, Couto S, Ren Y, Arcari A, Bertoldero G, Nonis A, Scarfò L, Calimeri T, Cecchetti C, Chiozzotto M, Govi S, Ponzoni M. Lenalidomide maintenance in patients with relapsed diffuse large B-cell lymphoma who are not eligible for autologous stem cell transplantation: an open label, single-arm, multicentre phase 2 trial. Lancet Haematol. 2017 Mar;4(3):e137-e146. Epub 2017 Feb 17. [https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(17)30016-9/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28219694 PubMed]
 ==Observation==
@@ Line 3,612: / Line 3,935: @@
 ===Regimen===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2288718/ Thompson et al. 2008 (SWOG 9438)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |IL-2
-|style="background-color:#ffffbf"|Did not meet primary endpoints of PFS/OS
+| style="background-color:#ffffbf" |Did not meet primary endpoints of PFS/OS
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682835/ Furman et al. 2011 (CALGB 9254)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |Anti-B4-bR
-|style="background-color:#ffffbf"|Did not meet primary endpoint of EFS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664033/ Gisselbrecht et al. 2010 (CORAL)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#Rituximab_monotherapy_2|Rituximab]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of EFS (*)
+| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS (*)
 |-
 |}
 ''No further treatment. Reported efficacy for CORAL is based on the 2012 update.''
 ====Preceding treatment====
 *SWOG 9438: Cyclophosphamide, Etoposide, TBI with autologous hematopoietic stem cell transplant
 *CORAL: [[#BEAM.2C_then_auto_HSCT|BEAM with autologous hematopoietic stem cell transplant]]
 ===References===
-# '''SWOG 9438:''' Thompson JA, Fisher RI, Leblanc M, Forman SJ, Press OW, Unger JM, Nademanee AP, Stiff PJ, Petersdorf SH, Fefer A. Total body irradiation, etoposide, cyclophosphamide, and autologous peripheral blood stem-cell transplantation followed by randomization to therapy with interleukin-2 versus observation for patients with non-Hodgkin lymphoma: results of a phase 3 randomized trial by the Southwest Oncology Group (SWOG 9438). Blood. 2008 Apr 15;111(8):4048-54. Epub 2008 Feb 6. [http://www.bloodjournal.org/content/111/8/4048.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2288718/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18256325 PubMed]
-# '''CALGB 9254:''' Furman RR, Grossbard ML, Johnson JL, Pecora AL, Cassileth PA, Jung SH, Peterson BA, Nadler LM, Freedman A, Bayer RL, Bartlett NL, Hurd DD, Cheson BD; Cancer Leukemia Group B; Eastern Cooperative Oncology Group. A phase III study of anti-B4-blocked ricin as adjuvant therapy post-autologous bone marrow transplant: CALGB 9254. Leuk Lymphoma. 2011 Apr;52(4):587-96. Epub 2011 Jan 28. [https://www.tandfonline.com/doi/abs/10.3109/10428194.2010.543714 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682835/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21275630 PubMed]
+#'''SWOG 9438:''' Thompson JA, Fisher RI, Leblanc M, Forman SJ, Press OW, Unger JM, Nademanee AP, Stiff PJ, Petersdorf SH, Fefer A. Total body irradiation, etoposide, cyclophosphamide, and autologous peripheral blood stem-cell transplantation followed by randomization to therapy with interleukin-2 versus observation for patients with non-Hodgkin lymphoma: results of a phase 3 randomized trial by the Southwest Oncology Group (SWOG 9438). Blood. 2008 Apr 15;111(8):4048-54. Epub 2008 Feb 6. [http://www.bloodjournal.org/content/111/8/4048.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2288718/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18256325 PubMed]
+#'''CALGB 9254:''' Furman RR, Grossbard ML, Johnson JL, Pecora AL, Cassileth PA, Jung SH, Peterson BA, Nadler LM, Freedman A, Bayer RL, Bartlett NL, Hurd DD, Cheson BD; Cancer Leukemia Group B; Eastern Cooperative Oncology Group. A phase III study of anti-B4-blocked ricin as adjuvant therapy post-autologous bone marrow transplant: CALGB 9254. Leuk Lymphoma. 2011 Apr;52(4):587-96. Epub 2011 Jan 28. [https://www.tandfonline.com/doi/abs/10.3109/10428194.2010.543714 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682835/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21275630 PubMed]
 <!-- Presented at the 45th Annual Meeting of the American Society of Clinical Oncology, June 4-6, 2011, Chicago, IL. -->
-# '''CORAL:''' Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Brière J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. Epub 2010 Jul 26. Erratum in: J Clin Oncol. 2012 May 20;30(15):1896. [http://jco.ascopubs.org/content/28/27/4184.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664033/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20660832 PubMed]
+#'''CORAL:''' Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Brière J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. Epub 2010 Jul 26. Erratum in: J Clin Oncol. 2012 May 20;30(15):1896. [http://jco.ascopubs.org/content/28/27/4184.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664033/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20660832 PubMed]
-## '''Update:''' Gisselbrecht C, Schmitz N, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Milpied NJ, Radford J, Ketterer N, Shpilberg O, Dührsen U, Hagberg H, Ma DD, Viardot A, Lowenthal R, Brière J, Salles G, Moskowitz CH, Glass B. Rituximab maintenance therapy after autologous stem-cell transplantation in patients with relapsed CD20(+) diffuse large B-cell lymphoma: final analysis of the collaborative trial in relapsed aggressive lymphoma. J Clin Oncol. 2012 Dec 20;30(36):4462-9. Epub 2012 Oct 22. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.12846/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646314/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23091101 PubMed]
+##'''Update:''' Gisselbrecht C, Schmitz N, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Milpied NJ, Radford J, Ketterer N, Shpilberg O, Dührsen U, Hagberg H, Ma DD, Viardot A, Lowenthal R, Brière J, Salles G, Moskowitz CH, Glass B. Rituximab maintenance therapy after autologous stem-cell transplantation in patients with relapsed CD20(+) diffuse large B-cell lymphoma: final analysis of the collaborative trial in relapsed aggressive lymphoma. J Clin Oncol. 2012 Dec 20;30(36):4462-9. Epub 2012 Oct 22. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.12846/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646314/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23091101 PubMed]
 ==Rituximab monotherapy {{#subobject:4a4553|Regimen=1}}==
@@ Line 3,653: / Line 3,978: @@
 ===Regimen {{#subobject:7bef48|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664033/ Gisselbrecht et al. 2010 (CORAL)]
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#1a9851" |Phase III (E-esc)
 |[[#Observation_2|Observation]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of EFS (*)
+| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS (*)
 |-
 |}
 ''Treatment begins on day +28. Reported efficacy is based on the 2012 update.''
 ====Preceding treatment====
 *[[#BEAM.2C_then_auto_HSCT|BEAM with autologous hematopoietic stem cell transplant]]
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 3,674: / Line 4,002: @@
 ===References===
 <!-- Presented at the 45th Annual Meeting of the American Society of Clinical Oncology, June 4-6, 2011, Chicago, IL. -->
-# '''CORAL:''' Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Brière J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. Epub 2010 Jul 26. Erratum in: J Clin Oncol. 2012 May 20;30(15):1896. [http://jco.ascopubs.org/content/28/27/4184.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664033/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20660832 PubMed]
-## '''Update:''' Gisselbrecht C, Schmitz N, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Milpied NJ, Radford J, Ketterer N, Shpilberg O, Dührsen U, Hagberg H, Ma DD, Viardot A, Lowenthal R, Brière J, Salles G, Moskowitz CH, Glass B. Rituximab maintenance therapy after autologous stem-cell transplantation in patients with relapsed CD20(+) diffuse large B-cell lymphoma: final analysis of the collaborative trial in relapsed aggressive lymphoma. J Clin Oncol. 2012 Dec 20;30(36):4462-9. Epub 2012 Oct 22. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.12846/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646314/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23091101 PubMed]
+#'''CORAL:''' Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Brière J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. Epub 2010 Jul 26. Erratum in: J Clin Oncol. 2012 May 20;30(15):1896. [http://jco.ascopubs.org/content/28/27/4184.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664033/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20660832 PubMed]
+##'''Update:''' Gisselbrecht C, Schmitz N, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Milpied NJ, Radford J, Ketterer N, Shpilberg O, Dührsen U, Hagberg H, Ma DD, Viardot A, Lowenthal R, Brière J, Salles G, Moskowitz CH, Glass B. Rituximab maintenance therapy after autologous stem-cell transplantation in patients with relapsed CD20(+) diffuse large B-cell lymphoma: final analysis of the collaborative trial in relapsed aggressive lymphoma. J Clin Oncol. 2012 Dec 20;30(36):4462-9. Epub 2012 Oct 22. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.12846/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646314/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23091101 PubMed]
 =Relapsed or refractory, further lines of therapy=
@@ Line 3,690: / Line 4,019: @@
 |}
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|Years of enrollment
+! style="width: 25%" |Years of enrollment
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363293/ Locke et al. 2017 (ZUMA-1)]
@@ Line 3,702: / Line 4,031: @@
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882485/ Nellapu et al. 2017 (ZUMA-1)]
 |2015-2016
-|style="background-color:#91cf61"|Phase II (RT)
+| style="background-color:#91cf61" |Phase II (RT)
 | style="background-color:#e0ecf4" |ORR: 82%
 |-
 |}
 ====Preceding treatment====
 *Lymphodepletion with [[Autologous_HSCT#FC|FC]]
 ====Immunotherapy====
 *[[Axicabtagene ciloleucel (Yescarta)]] target dose of 2 × 10<sup>6</sup> CAR T cells/kg IV once on day 0
 ====Supportive medications====
 *[[Acetaminophen (Tylenol)]] 650 mg PO once on day 0, approximately 60 minutes prior to [[Axicabtagene ciloleucel (Yescarta)]]
 *[[Diphenhydramine (Benadryl)]] 12.5 mg IV or PO once on day 0, approximately 60 minutes prior to [[Axicabtagene ciloleucel (Yescarta)]]
@@ Line 3,718: / Line 4,051: @@
 ===References===
-# '''Phase 1:''' Locke FL, Neelapu SS, Bartlett NL, Siddiqi T, Chavez JC, Hosing CM, Ghobadi A, Budde LE, Bot A, Rossi JM, Jiang Y, Xue AX, Elias M, Aycock J, Wiezorek J, Go WY. Phase 1 results of ZUMA-1: A multicenter study of KTE-C19 anti-CD19 CAR T cell therapy in refractory aggressive lymphoma. Mol Ther. 2017 Jan 4;25(1):285-295. Epub 2017 Jan 4. [http://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(16)45375-X link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363293/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/28129122 PubMed]
-# '''ZUMA-1:''' Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang D, Wiezorek J, Go WY. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017 Dec 28;377(26):2531-2544. Epub 2017 Dec 10. [https://www.nejm.org/doi/full/10.1056/NEJMoa1707447 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882485/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29226797 PubMed]
+#'''Phase 1:''' Locke FL, Neelapu SS, Bartlett NL, Siddiqi T, Chavez JC, Hosing CM, Ghobadi A, Budde LE, Bot A, Rossi JM, Jiang Y, Xue AX, Elias M, Aycock J, Wiezorek J, Go WY. Phase 1 results of ZUMA-1: A multicenter study of KTE-C19 anti-CD19 CAR T cell therapy in refractory aggressive lymphoma. Mol Ther. 2017 Jan 4;25(1):285-295. Epub 2017 Jan 4. [http://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(16)45375-X link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363293/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/28129122 PubMed]
+#'''ZUMA-1:''' Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang D, Wiezorek J, Go WY. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017 Dec 28;377(26):2531-2544. Epub 2017 Dec 10. [https://www.nejm.org/doi/full/10.1056/NEJMoa1707447 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882485/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29226797 PubMed]
 ==Bendamustine monotherapy {{#subobject:78231d|Regimen=1}}==
@@ Line 3,729: / Line 4,063: @@
 ===Regimen {{#subobject:e3e516|Variant=1}}===
 {| class="wikitable" style="width: 75%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 33%" |Study
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
+! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
 |[https://academic.oup.com/annonc/article/13/8/1285/143237 Weidmann et al. 2002]
-|style="background-color:#ffffbe"|Phase II, <20 pts
+| style="background-color:#ffffbe" |Phase II, <20 pts
 |44%
 |-
 |}
 ====Chemotherapy====
 *[[Bendamustine]] 120 mg/m<sup>2</sup> IV once per day on days 1 & 2
@@ Line 3,744: / Line 4,079: @@
 ===References===
-# Weidmann E, Kim SZ, Rost A, Schuppert H, Seipelt G, Hoelzer D, Mitrou PS. Bendamustine is effective in relapsed or refractory aggressive non-Hodgkin's lymphoma. Ann Oncol. 2002 Aug;13(8):1285-9. [https://academic.oup.com/annonc/article/13/8/1285/143237 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12181253 PubMed]
+#Weidmann E, Kim SZ, Rost A, Schuppert H, Seipelt G, Hoelzer D, Mitrou PS. Bendamustine is effective in relapsed or refractory aggressive non-Hodgkin's lymphoma. Ann Oncol. 2002 Aug;13(8):1285-9. [https://academic.oup.com/annonc/article/13/8/1285/143237 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12181253 PubMed]
 ==Blinatumomab monotherapy {{#subobject:4c5004|Regimen=1}}==
@@ Line 3,754: / Line 4,090: @@
 ===Regimen {{#subobject:94f800|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4797019/ Viardot et al. 2016 (MT103-208)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 3,764: / Line 4,100: @@
 ''Two dosing schemas were evaluated; this is the preferred dosing regimen, per the authors.''
 ====Chemotherapy====
 *[[Blinatumomab (Blincyto)]] as follows:
 **9 mcg/day IV continuous infusion during week 1, then
@@ Line 3,770: / Line 4,107: @@
 ====Supportive medications====
 *[[Dexamethasone (Decadron)]] 20 mg PO 6 to 12 hours before infusion start and dose increases, 20 mg PO 1 hour before infusion start and dose increases, and 8 mg PO three times per day for 2 days following infusion start and dose increases
 **Patients with neurologic symptoms or cytokine release syndrome received 8 mg IV or PO every 8 hours for up to 3 days, with a subsequent taper over 4 days
@@ Line 3,779: / Line 4,117: @@
 ===References===
 <!--Presented in abstract form at the 55th annual meeting (New Orleans, LA, December 2013) and the 56th annual meeting (San Francisco, CA, December 2014) of the American Society of Hematology; the 2015 annual meeting of the American Society of Clinical Oncology (Chicago, IL, June 2015); and the 13th International Conference on Malignant Lymphoma (Lugano, Switzerland, June 2015). -->
-# '''MT103-208:''' Viardot A, Goebeler ME, Hess G, Neumann S, Pfreundschuh M, Adrian N, Zettl F, Libicher M, Sayehli C, Stieglmaier J, Zhang A, Nagorsen D, Bargou RC. Phase 2 study of the bispecific T-cell engager (BiTE) antibody blinatumomab in relapsed/refractory diffuse large B-cell lymphoma. Blood. 2016 Mar 17;127(11):1410-6. Epub 2016 Jan 11. [http://www.bloodjournal.org/content/127/11/1410.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4797019/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26755709 PubMed]
+#'''MT103-208:''' Viardot A, Goebeler ME, Hess G, Neumann S, Pfreundschuh M, Adrian N, Zettl F, Libicher M, Sayehli C, Stieglmaier J, Zhang A, Nagorsen D, Bargou RC. Phase 2 study of the bispecific T-cell engager (BiTE) antibody blinatumomab in relapsed/refractory diffuse large B-cell lymphoma. Blood. 2016 Mar 17;127(11):1410-6. Epub 2016 Jan 11. [http://www.bloodjournal.org/content/127/11/1410.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4797019/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26755709 PubMed]
 ==BR {{#subobject:1bb486|Regimen=1}}==
@@ Line 3,790: / Line 4,129: @@
 ===Regimen variant #1, 6 cycles {{#subobject:87e6f7|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 50%"|Study
+! style="width: 50%" |Study
-!style="width: 50%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://jco.ascopubs.org/content/31/17/2103.full Ohmachi et al. 2013 (SymBio 2010001)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918114/ Vacirca et al. 2013 (PI-08904)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''Note: Bendamustine was given on days 2 & 3 in SymBio 2010001 and on days 1 & 2 in PI-08904.''
 ====Chemotherapy====
 *[[Bendamustine]] 120 mg/m<sup>2</sup> IV once per day on days 1 & 2 OR on days 2 & 3
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 ====Supportive medications====
 *Recommended PCP prophylaxis: [[Trimethoprim-Sulfamethoxazole (Bactrim DS)]]
 *Recommended VZV prophylaxis: [[Acyclovir (Zovirax)]]
@@ Line 3,813: / Line 4,154: @@
 ===Regimen variant #2, indefinite {{#subobject:87ea7c|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200343/ Dang et al. 2017 (B1931008)]
@@ Line 3,825: / Line 4,166: @@
 |}
 ====Chemotherapy====
 *[[Bendamustine]] 120 mg/m<sup>2</sup> IV once per day on days 1 & 2
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 3,832: / Line 4,174: @@
 ===References===
 <!-- Presented at the 48th Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2012, Chicago, IL. -->
-# '''SymBio 2010001:''' Ohmachi K, Niitsu N, Uchida T, Kim SJ, Ando K, Takahashi N, Takahashi N, Uike N, Eom HS, Chae YS, Terauchi T, Tateishi U, Tatsumi M, Kim WS, Tobinai K, Suh C, Ogura M. Multicenter phase II study of bendamustine plus rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol. 2013 Jun 10;31(17):2103-9. Epub 2013 May 6. [http://jco.ascopubs.org/content/31/17/2103.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23650408 PubMed]
-# '''PI-08904:''' Vacirca JL, Acs PI, Tabbara IA, Rosen PJ, Lee P, Lynam E. Bendamustine combined with rituximab for patients with relapsed or refractory diffuse large B cell lymphoma. Ann Hematol. 2014 Mar;93(3):403-9. Epub 2013 Aug 17. [http://link.springer.com/article/10.1007%2Fs00277-013-1879-x/fulltext.html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918114/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23955074 PubMed]
+#'''SymBio 2010001:''' Ohmachi K, Niitsu N, Uchida T, Kim SJ, Ando K, Takahashi N, Takahashi N, Uike N, Eom HS, Chae YS, Terauchi T, Tateishi U, Tatsumi M, Kim WS, Tobinai K, Suh C, Ogura M. Multicenter phase II study of bendamustine plus rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol. 2013 Jun 10;31(17):2103-9. Epub 2013 May 6. [http://jco.ascopubs.org/content/31/17/2103.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23650408 PubMed]
-# '''B1931008:''' Dang NH, Ogura M, Castaigne S, Fayad LE, Jerkeman M, Radford J, Pezzutto A, Bondarenko I, Stewart DA, Shnaidman M, Sullivan S, Vandendries E, Tobinai K, Ramchandren R, Hamlin PA, Giné E, Ando K. Randomized, phase 3 trial of inotuzumab ozogamicin plus rituximab versus chemotherapy plus rituximab for relapsed/refractory aggressive B-cell non-Hodgkin lymphoma. Br J Haematol. 2018 Aug;182(4):583-586. Epub 2017 Jul 5. [https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.14820 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200343/ link to PMC article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28677896 PubMed]
+#'''PI-08904:''' Vacirca JL, Acs PI, Tabbara IA, Rosen PJ, Lee P, Lynam E. Bendamustine combined with rituximab for patients with relapsed or refractory diffuse large B cell lymphoma. Ann Hematol. 2014 Mar;93(3):403-9. Epub 2013 Aug 17. [http://link.springer.com/article/10.1007%2Fs00277-013-1879-x/fulltext.html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918114/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23955074 PubMed]
+#'''B1931008:''' Dang NH, Ogura M, Castaigne S, Fayad LE, Jerkeman M, Radford J, Pezzutto A, Bondarenko I, Stewart DA, Shnaidman M, Sullivan S, Vandendries E, Tobinai K, Ramchandren R, Hamlin PA, Giné E, Ando K. Randomized, phase 3 trial of inotuzumab ozogamicin plus rituximab versus chemotherapy plus rituximab for relapsed/refractory aggressive B-cell non-Hodgkin lymphoma. Br J Haematol. 2018 Aug;182(4):583-586. Epub 2017 Jul 5. [https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.14820 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200343/ link to PMC article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28677896 PubMed]
 ==BR & Polatuzumab vedotin {{#subobject:1cc486|Regimen=1}}==
@@ Line 3,844: / Line 4,187: @@
 ===Regimen {{#subobject:26c6f7|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://clinicaltrials.gov/ct2/show/NCT02257567 See note (GO29365)]
+|[https://ascopubs.org/doi/pdf/10.1200/JCO.19.00172 GO29365]
-|{{#subobject:xx|ToDo=1}}
+|2014-2016{{#subobject:xx|ToDo=1}}
 | style="background-color:#1a9851" |Randomized Phase II (E-RT-esc)
 |[[#BR_2|BR]]
@@ Line 3,857: / Line 4,200: @@
 |-
 |}
-''Note: this study has not been published to our knowledge; these details are from ClinicalTrials.gov.''
+<br />
 ====Chemotherapy====
 *[[Bendamustine]] as follows:
 **Cycle 1: 90 mg/m<sup>2</sup> IV once per day on days 2 & 3
@@ Line 3,866: / Line 4,210: @@
 **Cycle 1: 1.8 mg/kg IV over 90 minutes once on day 2
 **Cycles 2 to 6: 1.8 mg/kg IV over 90 minutes once on day 1
 ===References===
-# '''GO29365:''' [https://clinicaltrials.gov/ct2/show/NCT02257567 CT.gov]
+#'''GO29365:''' Sehn LH, Herrera AF, Flowers CR, Kamdar MK, McMillan A, Hertzberg M, Assouline S, Kim TM, Kim WS, Ozcan M, Hirata J, Penuel E, Paulson JN, Cheng J, Ku G, Matasar MJ. Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. J Clin Oncol. 2020 Jan 10; 38(2):155-165. Epub 2019 Nov 6. [https://ascopubs.org/doi/full/10.1200/JCO.19.00172 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/31693429 link to pubmed] [https://clinicaltrials.gov/ct2/show/NCT02257567 CT.gov]
 ==Brentuximab vedotin monotherapy {{#subobject:d4dff2|Regimen=1}}==
@@ Line 3,877: / Line 4,223: @@
 ===Regimen {{#subobject:965d6b|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://www.bloodjournal.org/content/125/9/1394 Jacobsen et al. 2015 (SGN35-012)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''Jacobsen et al. 2015 treated patients with CD30+ non-Hodgkin lymphoma, as determined by IHC; the 2016 update describes a subgroup with undetectable CD30.''
 ====Chemotherapy====
 *[[Brentuximab vedotin (Adcetris)]] 1.8 mg/kg IV over 30 minutes once on day 1
@@ Line 3,892: / Line 4,239: @@
 ===References===
 <!-- '''Abstract:''' Nancy L. Bartlett, MD, Jeff P. Sharman, MD, Yasuhiro Oki, MD, Ranjana H. Advani, MD, Celeste M. Bello, MD, Jane N. Winter, MD, Yin Yang, MS, Dana A. Kennedy, PharmD and Eric D. Jacobsen, MD. A Phase 2 Study Of Brentuximab Vedotin In Patients With Relapsed Or Refractory CD30-Positive Non-Hodgkin Lymphomas: Interim Results In Patients With DLBCL and Other B-Cell Lymphomas. ASH Abstract 848. [https://ash.confex.com/ash/2013/webprogram/Paper59695.html link to abstract] -->
-# '''SGN35-012:''' Jacobsen ED, Sharman JP, Oki Y, Advani RH, Winter JN, Bello CM, Spitzer G, Palanca-Wessels MC, Kennedy DA, Levine P, Yang J, Bartlett NL. Brentuximab vedotin demonstrates objective responses in a phase 2 study of relapsed/refractory DLBCL with variable CD30 expression. Blood. 2015 Feb 26;125(9):1394-402. Epub 2015 Jan 8. [http://www.bloodjournal.org/content/125/9/1394 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25573987 PubMed]
+#'''SGN35-012:''' Jacobsen ED, Sharman JP, Oki Y, Advani RH, Winter JN, Bello CM, Spitzer G, Palanca-Wessels MC, Kennedy DA, Levine P, Yang J, Bartlett NL. Brentuximab vedotin demonstrates objective responses in a phase 2 study of relapsed/refractory DLBCL with variable CD30 expression. Blood. 2015 Feb 26;125(9):1394-402. Epub 2015 Jan 8. [http://www.bloodjournal.org/content/125/9/1394 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25573987 PubMed]
 <!-- # '''Abstract:''' Nancy L. Bartlett, MD, Mitchell R. Smith, MD, Ranjana Advani, MD, Tatyana Feldman, MD, Kerry J. Savage, MD MSc, Maria Corinna Palanca-Wessels, MD, PhD and Tanya Siddiqi, MD. Brentuximab Vedotin Monotherapy in DLBCL Patients with Undetectable CD30: Preliminary Results from a Phase 2 Study. ASH Annual Meeting 2014 Abstract 629 [https://ash.confex.com/ash/2014/webprogram/Paper67042.html link to abstract] -->
-## '''Update:''' Bartlett NL, Smith MR, Siddiqi T, Advani RH, O'Connor OA, Sharman JP, Feldman T, Savage KJ, Shustov AR, Diefenbach CS, Oki Y, Palanca-Wessels MC, Uttarwar M, Li M, Yang J, Jacobsen ED. Brentuximab vedotin activity in diffuse large B-cell lymphoma with CD30 undetectable by visual assessment of conventional immunohistochemistry. Leuk Lymphoma. 2017 Jul;58(7):1607-1616. Epub 2016 Nov 20. [https://www.tandfonline.com/doi/full/10.1080/10428194.2016.1256481 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27868471 PubMed]
+##'''Update:''' Bartlett NL, Smith MR, Siddiqi T, Advani RH, O'Connor OA, Sharman JP, Feldman T, Savage KJ, Shustov AR, Diefenbach CS, Oki Y, Palanca-Wessels MC, Uttarwar M, Li M, Yang J, Jacobsen ED. Brentuximab vedotin activity in diffuse large B-cell lymphoma with CD30 undetectable by visual assessment of conventional immunohistochemistry. Leuk Lymphoma. 2017 Jul;58(7):1607-1616. Epub 2016 Nov 20. [https://www.tandfonline.com/doi/full/10.1080/10428194.2016.1256481 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27868471 PubMed]
 ==Etoposide monotherapy {{#subobject:1ed00b|Regimen=1}}==
@@ Line 3,903: / Line 4,251: @@
 ===Regimen variant #1, IV (3 days/cycle) {{#subobject:7a80fc|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://clincancerres.aacrjournals.org/content/23/15/4127.long Czuczman et al. 2017 (DLC-001)]
@@ Line 3,915: / Line 4,263: @@
 |}
 ====Chemotherapy====
 *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
@@ Line 3,921: / Line 4,270: @@
 ===Regimen variant #2, IV (5 days/cycle) {{#subobject:1bece4|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70212-7/fulltext Pettengell et al. 2012 (PIX301)]
-|style="background-color:#91cf61"|Phase III, <20 pts in this arm (C)
+| style="background-color:#91cf61" |Phase III, <20 pts in this arm (C)
 |[[#Pixantrone_monotherapy|Pixantrone]]
-|style="background-color:#fc8d59"|Seems to have inferior CR/CRu rate
+| style="background-color:#fc8d59" |Seems to have inferior CR/CRu rate
 |-
 |[http://clincancerres.aacrjournals.org/content/23/15/4127.long Czuczman et al. 2017 (DLC-001)]
@@ Line 3,938: / Line 4,287: @@
 |}
 ====Chemotherapy====
 *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 5
@@ Line 3,944: / Line 4,294: @@
 ===Regimen variant #3, PO (10 days/cycle) {{#subobject:c6531a|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://clincancerres.aacrjournals.org/content/23/15/4127.long Czuczman et al. 2017 (DLC-001)]
@@ Line 3,956: / Line 4,306: @@
 |}
 ====Chemotherapy====
 *[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup> PO once per day on days 1 to 10
@@ Line 3,962: / Line 4,313: @@
 ===Regimen variant #4, PO (14 days/cycle) {{#subobject:f3bee1|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://clincancerres.aacrjournals.org/content/23/15/4127.long Czuczman et al. 2017 (DLC-001)]
@@ Line 3,974: / Line 4,325: @@
 |}
 ====Chemotherapy====
 *[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup> PO once per day on days 1 to 14
@@ Line 3,980: / Line 4,332: @@
 ===Regimen variant #5, PO (21 days/cycle) {{#subobject:929913|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://link.springer.com/chapter/10.1007/978-3-642-78350-0_29 Hainsworth et al. 1992]
@@ Line 3,991: / Line 4,343: @@
 |-
 |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70212-7/fulltext Pettengell et al. 2012 (PIX301)]
-|style="background-color:#91cf61"|Phase III, <20 pts in this arm (C)
+| style="background-color:#91cf61" |Phase III, <20 pts in this arm (C)
 |[[#Pixantrone_monotherapy|Pixantrone]]
-|style="background-color:#fc8d59"|Seems to have inferior CR/CRu rate
+| style="background-color:#fc8d59" |Seems to have inferior CR/CRu rate
 |-
 |[http://clincancerres.aacrjournals.org/content/23/15/4127.long Czuczman et al. 2017 (DLC-001)]
@@ Line 4,003: / Line 4,355: @@
 ''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.''
 ====Chemotherapy====
 *[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup> PO once per day on days 1 to 21
@@ Line 4,008: / Line 4,361: @@
 ===References===
-# Hainsworth JD, Johnson DH, Greco FA. Chronic etoposide schedules in the treatment of non-Hodgkin's lymphoma. Semin Oncol. 1992 Dec;19(6 Suppl 14):13-8. [https://link.springer.com/chapter/10.1007/978-3-642-78350-0_29 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/1488651 PubMed]
-# '''PIX301:''' Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70212-7/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22652183 PubMed]
+#Hainsworth JD, Johnson DH, Greco FA. Chronic etoposide schedules in the treatment of non-Hodgkin's lymphoma. Semin Oncol. 1992 Dec;19(6 Suppl 14):13-8. [https://link.springer.com/chapter/10.1007/978-3-642-78350-0_29 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/1488651 PubMed]
-# '''DLC-001:''' Czuczman MS, Trněný M, Davies A, Rule S, Linton KM, Wagner-Johnston N, Gascoyne RD, Slack GW, Brousset P, Eberhard DA, Hernandez-Ilizaliturri FJ, Salles G, Witzig TE, Zinzani PL, Wright GW, Staudt LM, Yang Y, Williams PM, Lih CJ, Russo J, Thakurta A, Hagner P, Fustier P, Song D, Lewis ID. A phase 2/3 multicenter, randomized, open-label study to compare the efficacy and safety of lenalidomide versus investigator's choice in patients with relapsed or refractory diffuse large B-cell lymphoma. Clin Cancer Res. 2017 Aug 1;23(15):4127-4137. Epub 2017 Apr 5. [http://clincancerres.aacrjournals.org/content/23/15/4127.long link to original article] '''contains verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/28381416 PubMed]
+#'''PIX301:''' Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70212-7/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22652183 PubMed]
+#'''DLC-001:''' Czuczman MS, Trněný M, Davies A, Rule S, Linton KM, Wagner-Johnston N, Gascoyne RD, Slack GW, Brousset P, Eberhard DA, Hernandez-Ilizaliturri FJ, Salles G, Witzig TE, Zinzani PL, Wright GW, Staudt LM, Yang Y, Williams PM, Lih CJ, Russo J, Thakurta A, Hagner P, Fustier P, Song D, Lewis ID. A phase 2/3 multicenter, randomized, open-label study to compare the efficacy and safety of lenalidomide versus investigator's choice in patients with relapsed or refractory diffuse large B-cell lymphoma. Clin Cancer Res. 2017 Aug 1;23(15):4127-4137. Epub 2017 Apr 5. [http://clincancerres.aacrjournals.org/content/23/15/4127.long link to original article] '''contains verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/28381416 PubMed]
 ==Everolimus monotherapy {{#subobject:fb3cbd|Regimen=1}}==
@@ Line 4,019: / Line 4,373: @@
 ===Regimen {{#subobject:9aafa|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049870/ Witzig et al. 2011]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Chemotherapy====
 *[[Everolimus (Afinitor)]] 10 mg PO once per day on an empty stomach
 ====Supportive medications====
 *"Patients could receive white blood cell growth factors, if neutropenia developed at physician's discretion. Erythropoietin treatment for anemia was permitted per standard guidelines."
@@ Line 4,035: / Line 4,391: @@
 ===References===
-# Witzig TE, Reeder CB, LaPlant BR, Gupta M, Johnston PB, Micallef IN, Porrata LF, Ansell SM, Colgan JP, Jacobsen ED, Ghobrial IM, Habermann TM. A phase II trial of the oral mTOR inhibitor everolimus in relapsed aggressive lymphoma. Leukemia. 2011 Feb;25(2):341-7. Epub 2010 Dec 7. [https://www.nature.com/leu/journal/v25/n2/full/leu2010226a.html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049870/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21135857 PubMed]
+#Witzig TE, Reeder CB, LaPlant BR, Gupta M, Johnston PB, Micallef IN, Porrata LF, Ansell SM, Colgan JP, Jacobsen ED, Ghobrial IM, Habermann TM. A phase II trial of the oral mTOR inhibitor everolimus in relapsed aggressive lymphoma. Leukemia. 2011 Feb;25(2):341-7. Epub 2010 Dec 7. [https://www.nature.com/leu/journal/v25/n2/full/leu2010226a.html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049870/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21135857 PubMed]
 ==Everolimus & Rituximab {{#subobject:bae86f|Regimen=1}}==
@@ Line 4,045: / Line 4,402: @@
 ===Regimen {{#subobject:9621eb|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659994/ Barnes et al. 2013 (MGH 09-002)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Chemotherapy====
 *[[Everolimus (Afinitor)]] as follows:
 **Cycle 1: 5 mg PO once per day on days 1 to 14, then 10 mg PO once per day on days 15 to 28
@@ Line 4,062: / Line 4,420: @@
 '''28-day cycle for 6 cycles'''
 ====Subsequent treatment====
 *Responders had the option of continuing everolimus alone for another 6 months
 ===References===
-# '''MGH 09-002:''' Barnes JA, Jacobsen E, Feng Y, Freedman A, Hochberg EP, LaCasce AS, Armand P, Joyce R, Sohani AR, Rodig SJ, Neuberg D, Fisher DC, Abramson JS. Everolimus in combination with rituximab induces complete responses in heavily pretreated diffuse large B-cell lymphoma. Haematologica. 2013 Apr;98(4):615-9. Epub 2012 Nov 9. [http://www.haematologica.org/content/98/4/615.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659994/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23144193 PubMed]
+#'''MGH 09-002:''' Barnes JA, Jacobsen E, Feng Y, Freedman A, Hochberg EP, LaCasce AS, Armand P, Joyce R, Sohani AR, Rodig SJ, Neuberg D, Fisher DC, Abramson JS. Everolimus in combination with rituximab induces complete responses in heavily pretreated diffuse large B-cell lymphoma. Haematologica. 2013 Apr;98(4):615-9. Epub 2012 Nov 9. [http://www.haematologica.org/content/98/4/615.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659994/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23144193 PubMed]
 ==Gemcitabine monotherapy {{#subobject:df3421|Regimen=1}}==
@@ Line 4,074: / Line 4,434: @@
 ===Regimen variant #1, bi-weekly {{#subobject:5776e8|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://clincancerres.aacrjournals.org/content/23/15/4127.long Czuczman et al. 2017 (DLC-001)]
@@ Line 4,086: / Line 4,446: @@
 |}
 ====Chemotherapy====
 *[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 15
@@ Line 4,092: / Line 4,453: @@
 ===Regimen variant #2, 3 out of 4 weeks x 6 {{#subobject:853906|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://clincancerres.aacrjournals.org/content/23/15/4127.long Czuczman et al. 2017 (DLC-001)]
@@ Line 4,104: / Line 4,465: @@
 |}
 ====Chemotherapy====
 *[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
@@ Line 4,110: / Line 4,472: @@
 ===Regimen variant #3, indefinite 3 out of 4 weeks {{#subobject:4d3a21|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://jco.ascopubs.org/content/17/12/3786.long Fosså et al. 1999]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70212-7/fulltext Pettengell et al. 2012 (PIX301)]
-|style="background-color:#91cf61"|Phase III, <20 pts in this arm (C)
+| style="background-color:#91cf61" |Phase III, <20 pts in this arm (C)
 |[[#Pixantrone_monotherapy|Pixantrone]]
-|style="background-color:#fc8d59"|Seems to have inferior CR/CRu rate
+| style="background-color:#fc8d59" |Seems to have inferior CR/CRu rate
 |-
 |}
 ''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.''
 ====Chemotherapy====
 *[[Gemcitabine (Gemzar)]] as follows:
 **Cycle 1: 1250 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15
@@ Line 4,135: / Line 4,498: @@
 ===References===
-# Fosså A, Santoro A, Hiddemann W, Truemper L, Niederle N, Buksmaui S, Bonadonna G, Seeber S, Nowrousian MR. Gemcitabine as a single agent in the treatment of relapsed or refractory aggressive non-Hodgkin's lymphoma. J Clin Oncol. 1999 Dec;17(12):3786-92. [http://jco.ascopubs.org/content/17/12/3786.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10577850 PubMed]
-# '''PIX301:''' Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70212-7/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22652183 PubMed]
+#Fosså A, Santoro A, Hiddemann W, Truemper L, Niederle N, Buksmaui S, Bonadonna G, Seeber S, Nowrousian MR. Gemcitabine as a single agent in the treatment of relapsed or refractory aggressive non-Hodgkin's lymphoma. J Clin Oncol. 1999 Dec;17(12):3786-92. [http://jco.ascopubs.org/content/17/12/3786.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10577850 PubMed]
-# '''DLC-001:''' Czuczman MS, Trněný M, Davies A, Rule S, Linton KM, Wagner-Johnston N, Gascoyne RD, Slack GW, Brousset P, Eberhard DA, Hernandez-Ilizaliturri FJ, Salles G, Witzig TE, Zinzani PL, Wright GW, Staudt LM, Yang Y, Williams PM, Lih CJ, Russo J, Thakurta A, Hagner P, Fustier P, Song D, Lewis ID. A phase 2/3 multicenter, randomized, open-label study to compare the efficacy and safety of lenalidomide versus investigator's choice in patients with relapsed or refractory diffuse large B-cell lymphoma. Clin Cancer Res. 2017 Aug 1;23(15):4127-4137. Epub 2017 Apr 5. [http://clincancerres.aacrjournals.org/content/23/15/4127.long link to original article] '''contains verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/28381416 PubMed]
+#'''PIX301:''' Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70212-7/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22652183 PubMed]
+#'''DLC-001:''' Czuczman MS, Trněný M, Davies A, Rule S, Linton KM, Wagner-Johnston N, Gascoyne RD, Slack GW, Brousset P, Eberhard DA, Hernandez-Ilizaliturri FJ, Salles G, Witzig TE, Zinzani PL, Wright GW, Staudt LM, Yang Y, Williams PM, Lih CJ, Russo J, Thakurta A, Hagner P, Fustier P, Song D, Lewis ID. A phase 2/3 multicenter, randomized, open-label study to compare the efficacy and safety of lenalidomide versus investigator's choice in patients with relapsed or refractory diffuse large B-cell lymphoma. Clin Cancer Res. 2017 Aug 1;23(15):4127-4137. Epub 2017 Apr 5. [http://clincancerres.aacrjournals.org/content/23/15/4127.long link to original article] '''contains verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/28381416 PubMed]
 ==Gemcitabine & Rituximab {{#subobject:1ba986|Regimen=1}}==
@@ Line 4,147: / Line 4,511: @@
 ===Regimen {{#subobject:cd26f7|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200343/ Dang et al. 2017 (B1931008)]
@@ Line 4,159: / Line 4,523: @@
 |}
 ====Chemotherapy====
 *[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 *[[Rituximab (Rituxan)]] as follows:
@@ Line 4,167: / Line 4,532: @@
 ===References===
-# '''B1931008:''' Dang NH, Ogura M, Castaigne S, Fayad LE, Jerkeman M, Radford J, Pezzutto A, Bondarenko I, Stewart DA, Shnaidman M, Sullivan S, Vandendries E, Tobinai K, Ramchandren R, Hamlin PA, Giné E, Ando K. Randomized, phase 3 trial of inotuzumab ozogamicin plus rituximab versus chemotherapy plus rituximab for relapsed/refractory aggressive B-cell non-Hodgkin lymphoma. Br J Haematol. 2018 Aug;182(4):583-586. Epub 2017 Jul 5. [https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.14820 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200343/ link to PMC article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28677896 PubMed]
+#'''B1931008:''' Dang NH, Ogura M, Castaigne S, Fayad LE, Jerkeman M, Radford J, Pezzutto A, Bondarenko I, Stewart DA, Shnaidman M, Sullivan S, Vandendries E, Tobinai K, Ramchandren R, Hamlin PA, Giné E, Ando K. Randomized, phase 3 trial of inotuzumab ozogamicin plus rituximab versus chemotherapy plus rituximab for relapsed/refractory aggressive B-cell non-Hodgkin lymphoma. Br J Haematol. 2018 Aug;182(4):583-586. Epub 2017 Jul 5. [https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.14820 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200343/ link to PMC article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28677896 PubMed]
 ==GVD {{#subobject:7102c5|Regimen=1}}==
@@ Line 4,177: / Line 4,543: @@
 ===Regimen {{#subobject:b6f37c|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://link.springer.com/article/10.1007%2Fs12032-012-0350-5 Bai et al. 2013]
-|style="background-color:#ffffbe"|Retrospective
+| style="background-color:#ffffbe" |Retrospective
 |-
 |}
 ====Chemotherapy====
 *[[Gemcitabine (Gemzar)]] 800 mg/m<sup>2</sup> IV once on day 1
 *[[Vinorelbine (Navelbine)]] 15 mg/m<sup>2</sup> IV once on day 1
@@ Line 4,192: / Line 4,559: @@
 ===References===
-# '''Retrospective:''' Bai B, Huang HQ, Cai QQ, Wang XX, Cai QC, Lin ZX, Gao Y, Xia Y, Bu Q, Guo Y. Promising long-term outcome of gemcitabine, vinorelbine, liposomal doxorubicin (GVD) in 14-day schedule as salvage regimen for patients with previously heavily treated Hodgkin's lymphoma and aggressive non-Hodgkin's lymphoma. Med Oncol. 2013 Mar;30(1):350. Epub 2013 Jan 18. [http://link.springer.com/article/10.1007%2Fs12032-012-0350-5 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23329307 PubMed]
+#'''Retrospective:''' Bai B, Huang HQ, Cai QQ, Wang XX, Cai QC, Lin ZX, Gao Y, Xia Y, Bu Q, Guo Y. Promising long-term outcome of gemcitabine, vinorelbine, liposomal doxorubicin (GVD) in 14-day schedule as salvage regimen for patients with previously heavily treated Hodgkin's lymphoma and aggressive non-Hodgkin's lymphoma. Med Oncol. 2013 Mar;30(1):350. Epub 2013 Jan 18. [http://link.springer.com/article/10.1007%2Fs12032-012-0350-5 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23329307 PubMed]
 ==Ibritumomab tiuxetan monotherapy {{#subobject:0b97a2|Regimen=1}}==
@@ Line 4,201: / Line 4,569: @@
 ===Regimen {{#subobject:5fd5b6|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://www.bloodjournal.org/content/110/1/54.long Morschhauser et al. 2007]
@@ Line 4,210: / Line 4,578: @@
 ''To be completed''
 ====Radioimmunotherapy====
-*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin) ]]
+*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]]
 ===References===
-# Morschhauser F, Illidge T, Huglo D, Martinelli G, Paganelli G, Zinzani PL, Rule S, Liberati AM, Milpied N, Hess G, Stein H, Kalmus J, Marcus R. Efficacy and safety of yttrium-90 ibritumomab tiuxetan in patients with relapsed or refractory diffuse large B-cell lymphoma not appropriate for autologous stem-cell transplantation. Blood. 2007 Jul 1;110(1):54-8. Epub 2007 Mar 26. [http://www.bloodjournal.org/content/110/1/54.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17387223 PubMed]
+#Morschhauser F, Illidge T, Huglo D, Martinelli G, Paganelli G, Zinzani PL, Rule S, Liberati AM, Milpied N, Hess G, Stein H, Kalmus J, Marcus R. Efficacy and safety of yttrium-90 ibritumomab tiuxetan in patients with relapsed or refractory diffuse large B-cell lymphoma not appropriate for autologous stem-cell transplantation. Blood. 2007 Jul 1;110(1):54-8. Epub 2007 Mar 26. [http://www.bloodjournal.org/content/110/1/54.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17387223 PubMed]
 ==Ibrutinib monotherapy {{#subobject:ba5ba9|Regimen=1}}==
@@ Line 4,222: / Line 4,593: @@
 ===Regimen {{#subobject:f4ee96|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.nature.com/articles/nm.3884 Wilson et al. 2015 (PCYC-1106-CA)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''Clinically meaningful responses were observed in the ABC subtype, only. Further clinical trials are currently underway.''
 ====Chemotherapy====
 *[[Ibrutinib (Imbruvica)]] 560 mg PO once per day
@@ Line 4,237: / Line 4,609: @@
 ===References===
 <!-- # '''Abstract:''' Wyndham H. Wilson, MD, PhD, John F. Gerecitano, MD, PhD, Andre Goy, MD, Sven de Vos, MD, PhD, Vaishalee P. Kenkre, MD, Paul M. Barr, MD, Kristie A. Blum, MD, Andrei R. Shustov, MD, Ranjana H. Advani, MD, Jason Lih, PhD, Mickey Williams, PhD, Roland Schmitz, PhD, Yandan Yang, PhD, Stefania Pittaluga, MD, PhD, George Wright, PhD, Lori A. Kunkel, MD, Jesse McGreivy, MD, Sriram Balasubramanian, PhD, Mei Cheng, PhD, Davina Moussa, Joseph J. Buggy, PhD and Louis M. Staudt, MD, PhD. The Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib (PCI-32765), Has Preferential Activity in the ABC Subtype of Relapsed/Refractory De Novo Diffuse Large B-Cell Lymphoma (DLBCL): Interim Results of a Multicenter, Open-Label, Phase 2 Study. Blood 120, a686 (2012). [https://ash.confex.com/ash/2012/webprogram/Paper48270.html link to abstract] -->
-# '''PCYC-1106-CA:''' Wilson WH, Young RM, Schmitz R, Yang Y, Pittaluga S, Wright G, Lih CJ, Williams PM, Shaffer AL, Gerecitano J, de Vos S, Goy A, Kenkre VP, Barr PM, Blum KA, Shustov A, Advani R, Fowler NH, Vose JM, Elstrom RL, Habermann TM, Barrientos JC, McGreivy J, Fardis M, Chang BY, Clow F, Munneke B, Moussa D, Beaupre DM, Staudt LM. Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma. Nat Med. 2015 Aug;21(8):922-6. Epub 2015 Jul 20. [https://www.nature.com/articles/nm.3884 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26193343 PubMed]
+#'''PCYC-1106-CA:''' Wilson WH, Young RM, Schmitz R, Yang Y, Pittaluga S, Wright G, Lih CJ, Williams PM, Shaffer AL, Gerecitano J, de Vos S, Goy A, Kenkre VP, Barr PM, Blum KA, Shustov A, Advani R, Fowler NH, Vose JM, Elstrom RL, Habermann TM, Barrientos JC, McGreivy J, Fardis M, Chang BY, Clow F, Munneke B, Moussa D, Beaupre DM, Staudt LM. Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma. Nat Med. 2015 Aug;21(8):922-6. Epub 2015 Jul 20. [https://www.nature.com/articles/nm.3884 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26193343 PubMed]
 ==Ifosfamide monotherapy {{#subobject:b9a669|Regimen=1}}==
@@ Line 4,246: / Line 4,619: @@
 ===Regimen {{#subobject:cd9499|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pubmed/1743622 Case et al. 1991 (CALGB 8552)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70212-7/fulltext Pettengell et al. 2012 (PIX301)]
-|style="background-color:#91cf61"|Phase III, <20 pts in this arm (C)
+| style="background-color:#91cf61" |Phase III, <20 pts in this arm (C)
 |[[#Pixantrone_monotherapy|Pixantrone]]
-|style="background-color:#fc8d59"|Seems to have inferior CR/CRu rate
+| style="background-color:#fc8d59" |Seems to have inferior CR/CRu rate
 |-
 |}
 ''Dose & schedule is as given in Pettengell et al. 2012. CALGB 8552 used a different dose & schedule. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.''
 ====Chemotherapy====
 *[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup> IV once per day on days 1 & 2
 ====Supportive medications====
 *[[Mesna (Mesnex)]] dose not specified
@@ Line 4,272: / Line 4,647: @@
 ===References===
-# '''CALGB 8552:''' Case DC Jr, Anderson J, Ervin TJ, Gottlieb A. Phase II trial of ifosfamide and mesna in previously treated patients with non-Hodgkin's lymphoma: Cancer and Leukemia Group B study 8552. Hematol Oncol. 1991 Jul-Oct;9(4-5):189-96. [https://www.ncbi.nlm.nih.gov/pubmed/1743622 PubMed]
-# '''Review:''' Webb MS, Saltman DL, Connors JM, Goldie JH. A literature review of single agent treatment of multiply relapsed aggressive non-Hodgkin's lymphoma. Leuk Lymphoma. 2002 May;43(5):975-82.  [https://www.tandfonline.com/doi/full/10.1080/10428190290021632 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12148908 PubMed]
+#'''CALGB 8552:''' Case DC Jr, Anderson J, Ervin TJ, Gottlieb A. Phase II trial of ifosfamide and mesna in previously treated patients with non-Hodgkin's lymphoma: Cancer and Leukemia Group B study 8552. Hematol Oncol. 1991 Jul-Oct;9(4-5):189-96. [https://www.ncbi.nlm.nih.gov/pubmed/1743622 PubMed]
-# '''PIX301:''' Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70212-7/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22652183 PubMed]
+#'''Review:''' Webb MS, Saltman DL, Connors JM, Goldie JH. A literature review of single agent treatment of multiply relapsed aggressive non-Hodgkin's lymphoma. Leuk Lymphoma. 2002 May;43(5):975-82.  [https://www.tandfonline.com/doi/full/10.1080/10428190290021632 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12148908 PubMed]
+#'''PIX301:''' Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70212-7/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22652183 PubMed]
 ==Lenalidomide monotherapy {{#subobject:f5ca0d|Regimen=1}}==
@@ Line 4,283: / Line 4,659: @@
 ===Regimen variant #1, low dose {{#subobject:64ba17|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://clincancerres.aacrjournals.org/content/23/15/4127.long Czuczman et al. 2017 (DLC-001)]
@@ Line 4,296: / Line 4,672: @@
 ''This dose was intended for patients with CrCl at least 30 but less than 60 mL/min/1.73m<sup>2</sup>.''
 ====Chemotherapy====
 *[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 21
@@ Line 4,302: / Line 4,679: @@
 ===Regimen variant #2, normal dose {{#subobject:7d5704|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://jco.ascopubs.org/content/26/30/4952.long Wiernik et al. 2008 (NHL-002)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 | style="background-color:#d3d3d3" |
 | style="background-color:#8c6bb1" |ORR: 35%
 |-
 |[http://annonc.oxfordjournals.org/content/22/7/1622.long Witzig et al. 2011 (NHL-003)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 | style="background-color:#d3d3d3" |
 | style="background-color:#8c6bb1" |ORR: 28%
@@ Line 4,324: / Line 4,701: @@
 |}
 ====Chemotherapy====
 *[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
@@ Line 4,329: / Line 4,707: @@
 ===References===
-# '''NHL-002:''' Wiernik PH, Lossos IS, Tuscano JM, Justice G, Vose JM, Cole CE, Lam W, McBride K, Wride K, Pietronigro D, Takeshita K, Ervin-Haynes A, Zeldis JB, Habermann TM. Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin's lymphoma. J Clin Oncol. 2008 Oct 20;26(30):4952-7. Epub 2008 Jul 7. [http://jco.ascopubs.org/content/26/30/4952.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18606983 PubMed]
-# '''NHL-003:''' Witzig TE, Vose JM, Zinzani PL, Reeder CB, Buckstein R, Polikoff JA, Bouabdallah R, Haioun C, Tilly H, Guo P, Pietronigro D, Ervin-Haynes AL, Czuczman MS. An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma. Ann Oncol. 2011 Jul;22(7):1622-7. Epub 2011 Jan 12. [http://annonc.oxfordjournals.org/content/22/7/1622.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21228334 PubMed]
+#'''NHL-002:''' Wiernik PH, Lossos IS, Tuscano JM, Justice G, Vose JM, Cole CE, Lam W, McBride K, Wride K, Pietronigro D, Takeshita K, Ervin-Haynes A, Zeldis JB, Habermann TM. Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin's lymphoma. J Clin Oncol. 2008 Oct 20;26(30):4952-7. Epub 2008 Jul 7. [http://jco.ascopubs.org/content/26/30/4952.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18606983 PubMed]
-# '''DLC-001:''' Czuczman MS, Trněný M, Davies A, Rule S, Linton KM, Wagner-Johnston N, Gascoyne RD, Slack GW, Brousset P, Eberhard DA, Hernandez-Ilizaliturri FJ, Salles G, Witzig TE, Zinzani PL, Wright GW, Staudt LM, Yang Y, Williams PM, Lih CJ, Russo J, Thakurta A, Hagner P, Fustier P, Song D, Lewis ID. A phase 2/3 multicenter, randomized, open-label study to compare the efficacy and safety of lenalidomide versus investigator's choice in patients with relapsed or refractory diffuse large B-cell lymphoma. Clin Cancer Res. 2017 Aug 1;23(15):4127-4137. Epub 2017 Apr 5. [http://clincancerres.aacrjournals.org/content/23/15/4127.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28381416 PubMed]
+#'''NHL-003:''' Witzig TE, Vose JM, Zinzani PL, Reeder CB, Buckstein R, Polikoff JA, Bouabdallah R, Haioun C, Tilly H, Guo P, Pietronigro D, Ervin-Haynes AL, Czuczman MS. An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma. Ann Oncol. 2011 Jul;22(7):1622-7. Epub 2011 Jan 12. [http://annonc.oxfordjournals.org/content/22/7/1622.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21228334 PubMed]
+#'''DLC-001:''' Czuczman MS, Trněný M, Davies A, Rule S, Linton KM, Wagner-Johnston N, Gascoyne RD, Slack GW, Brousset P, Eberhard DA, Hernandez-Ilizaliturri FJ, Salles G, Witzig TE, Zinzani PL, Wright GW, Staudt LM, Yang Y, Williams PM, Lih CJ, Russo J, Thakurta A, Hagner P, Fustier P, Song D, Lewis ID. A phase 2/3 multicenter, randomized, open-label study to compare the efficacy and safety of lenalidomide versus investigator's choice in patients with relapsed or refractory diffuse large B-cell lymphoma. Clin Cancer Res. 2017 Aug 1;23(15):4127-4137. Epub 2017 Apr 5. [http://clincancerres.aacrjournals.org/content/23/15/4127.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28381416 PubMed]
 ==Lenalidomide & Rituximab {{#subobject:d4c873|Regimen=1}}==
@@ Line 4,341: / Line 4,720: @@
 ===Regimen variant #1 {{#subobject:a04708|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.nature.com/leu/journal/v27/n9/full/leu201395a.html Wang et al. 2013 (MDACC 2005-0461)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Chemotherapy====
 *[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 1 to 21
 *[[Rituximab (Rituxan)]] as follows:
@@ Line 4,357: / Line 4,737: @@
 ===Regimen variant #2 {{#subobject:ad1aa9|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(11)00023-1/abstract Zinzani et al. 2011a]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Chemotherapy====
 *[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 1 to 21
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1 & 21
@@ Line 4,370: / Line 4,751: @@
 '''28-day cycle for 4 cycles'''
 ====Subsequent treatment====
 *SD or better: [[#Lenalidomide_monotherapy_2|Lenalidomide maintenance]]
 ===References===
-# Zinzani PL, Pellegrini C, Gandolfi L, Stefoni V, Quirini F, Derenzini E, Broccoli A, Argnani L, Pileri S, Baccarani M. Combination of lenalidomide and rituximab in elderly patients with relapsed or refractory diffuse large B-cell lymphoma: a phase 2 trial. Clin Lymphoma Myeloma Leuk. 2011 Dec;11(6):462-6. Epub 2011 May 4. [http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(11)00023-1/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21859554 PubMed]
-## '''Update:''' Zinzani PL, Pellegrini C, Derenzini E, Argnani L, Pileri S. Long-term efficacy of the combination of lenalidomide and rituximab in elderly relapsed/refractory diffuse large B-cell lymphoma patients. Hematol Oncol. 2013 Dec;31(4):223-4. Epub 2013 Apr 26. [https://onlinelibrary.wiley.com/doi/10.1002/hon.2049/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23620452 PubMed]
+#Zinzani PL, Pellegrini C, Gandolfi L, Stefoni V, Quirini F, Derenzini E, Broccoli A, Argnani L, Pileri S, Baccarani M. Combination of lenalidomide and rituximab in elderly patients with relapsed or refractory diffuse large B-cell lymphoma: a phase 2 trial. Clin Lymphoma Myeloma Leuk. 2011 Dec;11(6):462-6. Epub 2011 May 4. [http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(11)00023-1/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21859554 PubMed]
-# '''MDACC 2005-0461:''' Wang M, Fowler N, Wagner-Bartak N, Feng L, Romaguera J, Neelapu SS, Hagemeister F, Fanale M, Oki Y, Pro B, Shah J, Thomas S, Younes A, Hosing C, Zhang L, Newberry KJ, Desai M, Cheng N, Badillo M, Bejarano M, Chen Y, Young KH, Champlin R, Kwak L, Fayad L. Oral lenalidomide with rituximab in relapsed or refractory diffuse large cell, follicular and transformed lymphoma: a phase II clinical trial. Leukemia. 2013 Sep;27(9):1902-9. Epub 2013 Apr 2. [https://www.nature.com/leu/journal/v27/n9/full/leu201395a.html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23545991 PubMed]
+##'''Update:''' Zinzani PL, Pellegrini C, Derenzini E, Argnani L, Pileri S. Long-term efficacy of the combination of lenalidomide and rituximab in elderly relapsed/refractory diffuse large B-cell lymphoma patients. Hematol Oncol. 2013 Dec;31(4):223-4. Epub 2013 Apr 26. [https://onlinelibrary.wiley.com/doi/10.1002/hon.2049/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23620452 PubMed]
+#'''MDACC 2005-0461:''' Wang M, Fowler N, Wagner-Bartak N, Feng L, Romaguera J, Neelapu SS, Hagemeister F, Fanale M, Oki Y, Pro B, Shah J, Thomas S, Younes A, Hosing C, Zhang L, Newberry KJ, Desai M, Cheng N, Badillo M, Bejarano M, Chen Y, Young KH, Champlin R, Kwak L, Fayad L. Oral lenalidomide with rituximab in relapsed or refractory diffuse large cell, follicular and transformed lymphoma: a phase II clinical trial. Leukemia. 2013 Sep;27(9):1902-9. Epub 2013 Apr 2. [https://www.nature.com/leu/journal/v27/n9/full/leu201395a.html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23545991 PubMed]
 ==Mitoxantrone monotherapy {{#subobject:6e3e59|Regimen=1}}==
@@ Line 4,385: / Line 4,768: @@
 ===Regimen {{#subobject:b18da6|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pubmed/3282421 Bajetta et al. 1988a]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Chemotherapy====
 *[[Mitoxantrone (Novantrone)]] 14 mg/m<sup>2</sup> IV over 30 minutes once on day 1
@@ Line 4,398: / Line 4,782: @@
 ===References===
-# Bajetta E, Buzzoni R, Valagussa P, Bonadonna G. Mitoxantrone: an active agent in refractory non-Hodgkin's lymphomas. Am J Clin Oncol. 1988 Apr;11(2):100-3. '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/3282421 PubMed]
-# '''PIX301:''' Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70212-7/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22652183 PubMed]
+#Bajetta E, Buzzoni R, Valagussa P, Bonadonna G. Mitoxantrone: an active agent in refractory non-Hodgkin's lymphomas. Am J Clin Oncol. 1988 Apr;11(2):100-3. '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/3282421 PubMed]
+#'''PIX301:''' Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70212-7/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22652183 PubMed]
 ==Obinutuzumab monotherapy {{#subobject:9d2627|Regimen=1}}==
@@ Line 4,408: / Line 4,793: @@
 ===Regimen {{#subobject:7475e|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://www.bloodjournal.org/content/119/22/5126.long Salles et al. 2012 (GAUGUIN)]
-|style="background-color:#91cf61"|Phase I/II
+| style="background-color:#91cf61" |Phase I/II
 |-
 |}
 ''Note: this is the phase II dosing reported in Morschhauser et al. 2013.''
 ====Chemotherapy====
 *[[Obinutuzumab (Gazyva)]] as follows:
 **Cycle 1: 1600 mg (diluted to 10 mg/mL) IV once per day on days 1 & 8
@@ Line 4,423: / Line 4,809: @@
 ====Supportive medications====
 *[[Acetaminophen (Tylenol)]] or paracetamol 650 to 1000 mg PO once per infusion, 30 minutes prior to [[Obinutuzumab (Gazyva)]]
 *[[:Category:Antihistamines|"An antihistamine"]] once per infusion, 30 minutes prior to [[Obinutuzumab (Gazyva)]]
@@ Line 4,433: / Line 4,820: @@
 ===References===
-# '''GAUGUIN:''' Salles G, Morschhauser F, Lamy T, Milpied N, Thieblemont C, Tilly H, Bieska G, Asikanius E, Carlile D, Birkett J, Pisa P, Cartron G. Phase 1 study results of the type II glycoengineered humanized anti-CD20 monoclonal antibody obinutuzumab (GA101) in B-cell lymphoma patients. Blood. 2012 May 31;119(22):5126-32. Epub 2012 Mar 19. [http://www.bloodjournal.org/content/119/22/5126.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22431570 PubMed]
-## '''Subgroup analysis:''' Morschhauser FA, Cartron G, Thieblemont C, Solal-Céligny P, Haioun C, Bouabdallah R, Feugier P, Bouabdallah K, Asikanius E, Lei G, Wenger M, Wassner-Fritsch E, Salles GA. Obinutuzumab (GA101) monotherapy in relapsed/refractory diffuse large B-cell lymphoma or mantle-cell lymphoma: results from the phase II GAUGUIN study. J Clin Oncol. 2013 Aug 10;31(23):2912-9. Epub 2013 Jul 8. [http://jco.ascopubs.org/content/31/23/2912.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23835718 PubMed]
+#'''GAUGUIN:''' Salles G, Morschhauser F, Lamy T, Milpied N, Thieblemont C, Tilly H, Bieska G, Asikanius E, Carlile D, Birkett J, Pisa P, Cartron G. Phase 1 study results of the type II glycoengineered humanized anti-CD20 monoclonal antibody obinutuzumab (GA101) in B-cell lymphoma patients. Blood. 2012 May 31;119(22):5126-32. Epub 2012 Mar 19. [http://www.bloodjournal.org/content/119/22/5126.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22431570 PubMed]
-## '''Subgroup analysis:''' Salles GA, Morschhauser F, Solal-Céligny P, Thieblemont C, Lamy T, Tilly H, Gyan E, Lei G, Wenger M, Wassner-Fritsch E, Cartron G. Obinutuzumab (GA101) in patients with relapsed/refractory indolent non-Hodgkin lymphoma: results from the phase II GAUGUIN study. J Clin Oncol. 2013 Aug 10;31(23):2920-6. Epub 2013 Jul 8. [http://jco.ascopubs.org/content/31/23/2920.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23835715 PubMed]
+##'''Subgroup analysis:''' Morschhauser FA, Cartron G, Thieblemont C, Solal-Céligny P, Haioun C, Bouabdallah R, Feugier P, Bouabdallah K, Asikanius E, Lei G, Wenger M, Wassner-Fritsch E, Salles GA. Obinutuzumab (GA101) monotherapy in relapsed/refractory diffuse large B-cell lymphoma or mantle-cell lymphoma: results from the phase II GAUGUIN study. J Clin Oncol. 2013 Aug 10;31(23):2912-9. Epub 2013 Jul 8. [http://jco.ascopubs.org/content/31/23/2912.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23835718 PubMed]
-## '''Subgroup analysis:''' Cartron G, de Guibert S, Dilhuydy MS, Morschhauser F, Leblond V, Dupuis J, Mahe B, Bouabdallah R, Lei G, Wenger M, Wassner-Fritsch E, Hallek M. Obinutuzumab (GA101) in relapsed/refractory chronic lymphocytic leukemia: final data from the phase 1/2 GAUGUIN study. Blood. 2014 Oct 2;124(14):2196-202. Epub 2014 Aug 20. [http://www.bloodjournal.org/content/124/14/2196 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25143487 PubMed]
+##'''Subgroup analysis:''' Salles GA, Morschhauser F, Solal-Céligny P, Thieblemont C, Lamy T, Tilly H, Gyan E, Lei G, Wenger M, Wassner-Fritsch E, Cartron G. Obinutuzumab (GA101) in patients with relapsed/refractory indolent non-Hodgkin lymphoma: results from the phase II GAUGUIN study. J Clin Oncol. 2013 Aug 10;31(23):2920-6. Epub 2013 Jul 8. [http://jco.ascopubs.org/content/31/23/2920.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23835715 PubMed]
+##'''Subgroup analysis:''' Cartron G, de Guibert S, Dilhuydy MS, Morschhauser F, Leblond V, Dupuis J, Mahe B, Bouabdallah R, Lei G, Wenger M, Wassner-Fritsch E, Hallek M. Obinutuzumab (GA101) in relapsed/refractory chronic lymphocytic leukemia: final data from the phase 1/2 GAUGUIN study. Blood. 2014 Oct 2;124(14):2196-202. Epub 2014 Aug 20. [http://www.bloodjournal.org/content/124/14/2196 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25143487 PubMed]
 ==Ofatumumab monotherapy {{#subobject:5ba252|Regimen=1}}==
@@ Line 4,446: / Line 4,834: @@
 ===Regimen {{#subobject:4f5008|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/bjh.12537/full Coiffier et al. 2013 (415 Study)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Chemotherapy====
 *[[Ofatumumab (Arzerra)]] as follows:
 **Cycle 1: 300 mg IV once on day 1, then 1000 mg IV once per day on days 8, 15, 22
@@ Line 4,459: / Line 4,848: @@
 ====Supportive medications====
 *[[Acetaminophen (Tylenol)]] (or equivalent) 1000 mg PO once per day on days 1, 8, 15, 22; 30 minutes to 2 hours prior to [[Ofatumumab (Arzerra)]]
 *[[Cetirizine (Zyrtec)]] (or equivalent) 10 mg PO once per day on days 1, 8, 15, 22; 30 minutes to 2 hours prior to [[Ofatumumab (Arzerra)]]
@@ Line 4,466: / Line 4,856: @@
 ===References===
-# '''415 Study:''' Coiffier B, Radford J, Bosly A, Martinelli G, Verhoef G, Barca G, Davies A, Decaudin D, Gallop-Evans E, Padmanabhan-Iyer S, Van Eygen K, Wu KL, Gupta IV, Lin TS, Goldstein N, Jewell RC, Winter P, Lisby S; 415 study investigators. A multicentre, phase II trial of ofatumumab monotherapy in relapsed/progressive diffuse large B-cell lymphoma. Br J Haematol. 2013 Nov;163(3):334-42. Epub 2013 Aug 23. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.12537/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24032456 PubMed]
+#'''415 Study:''' Coiffier B, Radford J, Bosly A, Martinelli G, Verhoef G, Barca G, Davies A, Decaudin D, Gallop-Evans E, Padmanabhan-Iyer S, Van Eygen K, Wu KL, Gupta IV, Lin TS, Goldstein N, Jewell RC, Winter P, Lisby S; 415 study investigators. A multicentre, phase II trial of ofatumumab monotherapy in relapsed/progressive diffuse large B-cell lymphoma. Br J Haematol. 2013 Nov;163(3):334-42. Epub 2013 Aug 23. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.12537/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24032456 PubMed]
 ==Oxaliplatin monotherapy {{#subobject:308526|Regimen=1}}==
@@ Line 4,475: / Line 4,866: @@
 ===Regimen variant #1, 100 mg/m<sup>2</sup> {{#subobject:1fc8c3|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://annonc.oxfordjournals.org/content/10/3/351.long Germann et al. 1999]
-|style="background-color:#ffffbe"|Phase II, <20 pts in this subgroup
+| style="background-color:#ffffbe" |Phase II, <20 pts in this subgroup
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70212-7/fulltext Pettengell et al. 2012 (PIX301)]
-|style="background-color:#91cf61"|Phase III, <20 pts in this arm (C)
+| style="background-color:#91cf61" |Phase III, <20 pts in this arm (C)
 |[[#Pixantrone_monotherapy|Pixantrone]]
-|style="background-color:#fc8d59"|Seems to have inferior CR/CRu rate
+| style="background-color:#fc8d59" |Seems to have inferior CR/CRu rate
 |-
 |[http://clincancerres.aacrjournals.org/content/23/15/4127.long Czuczman et al. 2017 (DLC-001)]
@@ Line 4,498: / Line 4,889: @@
 ''Germann et al. give a range of 100 to 130 mg/m<sup>2</sup>. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.''
 ====Chemotherapy====
 *[[Oxaliplatin (Eloxatin)]] 100 mg/m<sup>2</sup> IV once on day 1
@@ Line 4,504: / Line 4,896: @@
 ===Regimen variant #2, 130 mg/m<sup>2</sup> {{#subobject:1bc18a|Variant=1}}===
 {| class="wikitable" style="width: 75%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 33%" |Study
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
+! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
 |[http://annonc.oxfordjournals.org/content/10/3/351.long Germann et al. 1999]
-|style="background-color:#ffffbe"|Phase II, <20 pts in this subgroup
+| style="background-color:#ffffbe" |Phase II, <20 pts in this subgroup
 | style="background-color:#d3d3d3" |
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1002/cncr.21219/full Oki et al. 2005]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 | style="background-color:#8c6bb1" |ORR: 27% (95% CI, 13–47)
 |-
@@ Line 4,519: / Line 4,911: @@
 ''Germann et al. give a range of 100 to 130 mg/m<sup>2</sup>.''
 ====Chemotherapy====
 *[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1
@@ Line 4,524: / Line 4,917: @@
 ===References===
-# Germann N, Brienza S, Rotarski M, Emile JF, Di Palma M, Musset M, Reynes M, Soulié P, Cvitkovic E, Misset JL. Preliminary results on the activity of oxaliplatin (L-OHP) in refractory/recurrent non-Hodgkin's lymphoma patients. Ann Oncol. 1999 Mar;10(3):351-4. [http://annonc.oxfordjournals.org/content/10/3/351.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10355582 PubMed]
-# '''Review:''' Webb MS, Saltman DL, Connors JM, Goldie JH. A literature review of single agent treatment of multiply relapsed aggressive non-Hodgkin's lymphoma. Leuk Lymphoma. 2002 May;43(5):975-82.  [https://www.tandfonline.com/doi/full/10.1080/10428190290021632 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12148908 PubMed]
+#Germann N, Brienza S, Rotarski M, Emile JF, Di Palma M, Musset M, Reynes M, Soulié P, Cvitkovic E, Misset JL. Preliminary results on the activity of oxaliplatin (L-OHP) in refractory/recurrent non-Hodgkin's lymphoma patients. Ann Oncol. 1999 Mar;10(3):351-4. [http://annonc.oxfordjournals.org/content/10/3/351.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10355582 PubMed]
-# Oki Y, McLaughlin P, Pro B, Hagemeister FB, Bleyer A, Loyer E, Younes A. Phase II study of oxaliplatin in patients with recurrent or refractory non-Hodgkin lymphoma. Cancer. 2005 Aug 15;104(4):781-7. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.21219/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15973667 PubMed]
+#'''Review:''' Webb MS, Saltman DL, Connors JM, Goldie JH. A literature review of single agent treatment of multiply relapsed aggressive non-Hodgkin's lymphoma. Leuk Lymphoma. 2002 May;43(5):975-82.  [https://www.tandfonline.com/doi/full/10.1080/10428190290021632 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12148908 PubMed]
-# '''PIX301:''' Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70212-7/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22652183 PubMed]
+#Oki Y, McLaughlin P, Pro B, Hagemeister FB, Bleyer A, Loyer E, Younes A. Phase II study of oxaliplatin in patients with recurrent or refractory non-Hodgkin lymphoma. Cancer. 2005 Aug 15;104(4):781-7. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.21219/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15973667 PubMed]
-# '''DLC-001:''' Czuczman MS, Trněný M, Davies A, Rule S, Linton KM, Wagner-Johnston N, Gascoyne RD, Slack GW, Brousset P, Eberhard DA, Hernandez-Ilizaliturri FJ, Salles G, Witzig TE, Zinzani PL, Wright GW, Staudt LM, Yang Y, Williams PM, Lih CJ, Russo J, Thakurta A, Hagner P, Fustier P, Song D, Lewis ID. A phase 2/3 multicenter, randomized, open-label study to compare the efficacy and safety of lenalidomide versus investigator's choice in patients with relapsed or refractory diffuse large B-cell lymphoma. Clin Cancer Res. 2017 Aug 1;23(15):4127-4137. Epub 2017 Apr 5. [http://clincancerres.aacrjournals.org/content/23/15/4127.long link to original article] '''contains verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/28381416 PubMed]
+#'''PIX301:''' Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70212-7/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22652183 PubMed]
+#'''DLC-001:''' Czuczman MS, Trněný M, Davies A, Rule S, Linton KM, Wagner-Johnston N, Gascoyne RD, Slack GW, Brousset P, Eberhard DA, Hernandez-Ilizaliturri FJ, Salles G, Witzig TE, Zinzani PL, Wright GW, Staudt LM, Yang Y, Williams PM, Lih CJ, Russo J, Thakurta A, Hagner P, Fustier P, Song D, Lewis ID. A phase 2/3 multicenter, randomized, open-label study to compare the efficacy and safety of lenalidomide versus investigator's choice in patients with relapsed or refractory diffuse large B-cell lymphoma. Clin Cancer Res. 2017 Aug 1;23(15):4127-4137. Epub 2017 Apr 5. [http://clincancerres.aacrjournals.org/content/23/15/4127.long link to original article] '''contains verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/28381416 PubMed]
 ==Panobinostat monotherapy {{#subobject:6b0341|Regimen=1}}==
@@ Line 4,538: / Line 4,932: @@
 ===Regimen {{#subobject:d71d7c|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972610/ Assouline et al. 2016 (Q-CROC-02)]
-|style="background-color:#1a9851"|Randomized Phase II (E-de-esc)
+| style="background-color:#1a9851" |Randomized Phase II (E-de-esc)
 |[[#Panobinostat_.26_Rituximab|Panobinostat & Rituximab]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
+| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 |-
 |}
 ''Note: patients had a median of 2 prior treatments (range 1-8).''
 ====Chemotherapy====
 *[[Panobinostat (Farydak)]] 30 mg PO three times per week (e.g., MWF)
@@ Line 4,556: / Line 4,951: @@
 ===References===
-# '''Q-CROC-02:''' Assouline SE, Nielsen TH, Yu S, Alcaide M, Chong L, MacDonald D, Tosikyan A, Kukreti V, Kezouh A, Petrogiannis-Haliotis T, Albuquerque M, Fornika D, Alamouti S, Froment R, Greenwood CM, Oros KK, Camglioglu E, Sharma A, Christodoulopoulos R, Rousseau C, Johnson N, Crump M, Morin RD, Mann KK. Phase 2 study of panobinostat with or without rituximab in relapsed diffuse large B-cell lymphoma. Blood. 2016 Jul 14;128(2):185-94. Epub 2016 May 10. [http://www.bloodjournal.org/content/128/2/185.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972610/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27166360 PubMed]
+#'''Q-CROC-02:''' Assouline SE, Nielsen TH, Yu S, Alcaide M, Chong L, MacDonald D, Tosikyan A, Kukreti V, Kezouh A, Petrogiannis-Haliotis T, Albuquerque M, Fornika D, Alamouti S, Froment R, Greenwood CM, Oros KK, Camglioglu E, Sharma A, Christodoulopoulos R, Rousseau C, Johnson N, Crump M, Morin RD, Mann KK. Phase 2 study of panobinostat with or without rituximab in relapsed diffuse large B-cell lymphoma. Blood. 2016 Jul 14;128(2):185-94. Epub 2016 May 10. [http://www.bloodjournal.org/content/128/2/185.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972610/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27166360 PubMed]
 ==Panobinostat & Rituximab {{#subobject:f7bdff|Regimen=1}}==
@@ Line 4,566: / Line 4,962: @@
 ===Regimen {{#subobject:cc78db|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972610/ Assouline et al. 2016 (Q-CROC-02)]
-|style="background-color:#91cf61"|Randomized Phase II, <20 pts (E-esc)
+| style="background-color:#91cf61" |Randomized Phase II, <20 pts (E-esc)
 |[[#Panobinostat_monotherapy|Panobinostat]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
+| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 |-
 |}
 ''Note: patients had a median of 3 prior treatments (range 2-9).''
 ====Chemotherapy====
 *[[Panobinostat (Farydak)]] 30 mg PO three times per week (e.g., MWF)
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 4,585: / Line 4,982: @@
 ===References===
-# '''Q-CROC-02:''' Assouline SE, Nielsen TH, Yu S, Alcaide M, Chong L, MacDonald D, Tosikyan A, Kukreti V, Kezouh A, Petrogiannis-Haliotis T, Albuquerque M, Fornika D, Alamouti S, Froment R, Greenwood CM, Oros KK, Camglioglu E, Sharma A, Christodoulopoulos R, Rousseau C, Johnson N, Crump M, Morin RD, Mann KK. Phase 2 study of panobinostat with or without rituximab in relapsed diffuse large B-cell lymphoma. Blood. 2016 Jul 14;128(2):185-94. Epub 2016 May 10. [http://www.bloodjournal.org/content/128/2/185.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972610/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27166360 PubMed]
+#'''Q-CROC-02:''' Assouline SE, Nielsen TH, Yu S, Alcaide M, Chong L, MacDonald D, Tosikyan A, Kukreti V, Kezouh A, Petrogiannis-Haliotis T, Albuquerque M, Fornika D, Alamouti S, Froment R, Greenwood CM, Oros KK, Camglioglu E, Sharma A, Christodoulopoulos R, Rousseau C, Johnson N, Crump M, Morin RD, Mann KK. Phase 2 study of panobinostat with or without rituximab in relapsed diffuse large B-cell lymphoma. Blood. 2016 Jul 14;128(2):185-94. Epub 2016 May 10. [http://www.bloodjournal.org/content/128/2/185.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972610/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27166360 PubMed]
 ==Pixantrone monotherapy {{#subobject:bedd78|Regimen=1}}==
@@ Line 4,594: / Line 4,992: @@
 ===Regimen {{#subobject:7fef70|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70212-7/abstract Pettengell et al. 2012 (PIX301)]
-|style="background-color:#1a9851"|Phase III (E-switch-ic)
+| style="background-color:#1a9851" |Phase III (E-switch-ic)
 |Investigator's choice of:<br> 1. [[#Etoposide_monotherapy|Etoposide]]<br> 2. [[#Gemcitabine_monotherapy|Gemcitabine]]<br> 3. [[#Ifosfamide_monotherapy|Ifosfamide]]<br> 4. [[#Mitoxantrone_monotherapy|Mitoxantrone]]<br> 5. [[#Oxaliplatin_monotherapy|Oxaliplatin]]<br> 6. [[#Vinorelbine_monotherapy|Vinorelbine]]
-|style="background-color:#91cf60"|Seems to have superior CR/CRu rate
+| style="background-color:#91cf60" |Seems to have superior CR/CRu rate
 |-
 |}
 ====Chemotherapy====
 *[[Pixantrone (Pixuvri)]] 85 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
@@ Line 4,611: / Line 5,010: @@
 ===References===
-# '''PIX301:''' Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70212-7/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22652183 PubMed]
-## '''Post-hoc analysis:''' Pettengell R, Sebban C, Zinzani PL, Derigs HG, Kravchenko S, Singer JW, Theocharous P, Wang L, Pavlyuk M, Makhloufi KM, Coiffier B. Monotherapy with pixantrone in histologically confirmed relapsed or refractory aggressive B-cell non-Hodgkin lymphoma: post-hoc analyses from a phase III trial. Br J Haematol. 2016 Sep;174(5):692-9. Epub 2016 Apr 26. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.14101/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5074333/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27118109 PubMed]
+#'''PIX301:''' Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70212-7/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22652183 PubMed]
+##'''Post-hoc analysis:''' Pettengell R, Sebban C, Zinzani PL, Derigs HG, Kravchenko S, Singer JW, Theocharous P, Wang L, Pavlyuk M, Makhloufi KM, Coiffier B. Monotherapy with pixantrone in histologically confirmed relapsed or refractory aggressive B-cell non-Hodgkin lymphoma: post-hoc analyses from a phase III trial. Br J Haematol. 2016 Sep;174(5):692-9. Epub 2016 Apr 26. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.14101/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5074333/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27118109 PubMed]
 ==Rituximab monotherapy {{#subobject:d826ec|Regimen=1}}==
@@ Line 4,621: / Line 5,021: @@
 ===Regimen {{#subobject:99a6d0|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://www.bloodjournal.org/content/92/6/1927.long Coiffier et al. 1998]
@@ Line 4,638: / Line 5,038: @@
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] as follows:
 **Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
@@ Line 4,645: / Line 5,046: @@
 ===References===
-# Coiffier B, Haioun C, Ketterer N, Engert A, Tilly H, Ma D, Johnson P, Lister A, Feuring-Buske M, Radford JA, Capdeville R, Diehl V, Reyes F. Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: a multicenter phase II study. Blood. 1998 Sep 15;92(6):1927-32. [http://www.bloodjournal.org/content/92/6/1927.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9731049 PubMed]
-# '''DLC-001:''' Czuczman MS, Trněný M, Davies A, Rule S, Linton KM, Wagner-Johnston N, Gascoyne RD, Slack GW, Brousset P, Eberhard DA, Hernandez-Ilizaliturri FJ, Salles G, Witzig TE, Zinzani PL, Wright GW, Staudt LM, Yang Y, Williams PM, Lih CJ, Russo J, Thakurta A, Hagner P, Fustier P, Song D, Lewis ID. A phase 2/3 multicenter, randomized, open-label study to compare the efficacy and safety of lenalidomide versus investigator's choice in patients with relapsed or refractory diffuse large B-cell lymphoma. Clin Cancer Res. 2017 Aug 1;23(15):4127-4137. Epub 2017 Apr 5. [http://clincancerres.aacrjournals.org/content/23/15/4127.long link to original article] '''contains verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/28381416 PubMed]
+#Coiffier B, Haioun C, Ketterer N, Engert A, Tilly H, Ma D, Johnson P, Lister A, Feuring-Buske M, Radford JA, Capdeville R, Diehl V, Reyes F. Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: a multicenter phase II study. Blood. 1998 Sep 15;92(6):1927-32. [http://www.bloodjournal.org/content/92/6/1927.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9731049 PubMed]
+#'''DLC-001:''' Czuczman MS, Trněný M, Davies A, Rule S, Linton KM, Wagner-Johnston N, Gascoyne RD, Slack GW, Brousset P, Eberhard DA, Hernandez-Ilizaliturri FJ, Salles G, Witzig TE, Zinzani PL, Wright GW, Staudt LM, Yang Y, Williams PM, Lih CJ, Russo J, Thakurta A, Hagner P, Fustier P, Song D, Lewis ID. A phase 2/3 multicenter, randomized, open-label study to compare the efficacy and safety of lenalidomide versus investigator's choice in patients with relapsed or refractory diffuse large B-cell lymphoma. Clin Cancer Res. 2017 Aug 1;23(15):4127-4137. Epub 2017 Apr 5. [http://clincancerres.aacrjournals.org/content/23/15/4127.long link to original article] '''contains verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/28381416 PubMed]
 ==R-BL {{#subobject:fe578a|Regimen=1}}==
@@ Line 4,657: / Line 5,059: @@
 ===Regimen {{#subobject:f063a7|Variant=1}}===
 {| class="wikitable" style="width: 75%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 33%" |Study
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
+! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/bjh.14049/abstract Hitz et al. 2016 (SAKK 38/08)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |ORR: 61% (95% CI 45-76%)
 |-
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Bendamustine]] 70 mg/m<sup>2</sup> IV once per day on days 1 & 2
@@ Line 4,674: / Line 5,077: @@
 ===References===
-# Hitz F, Zucca E, Pabst T, Fischer N, Cairoli A, Samaras P, Caspar CB, Mach N, Krasniqi F, Schmidt A, Rothermundt C, Enoiu M, Eckhardt K, Berardi Vilei S, Rondeau S, Mey U. Rituximab, bendamustine and lenalidomide in patients with aggressive B-cell lymphoma not eligible for anthracycline-based therapy or intensive salvage chemotherapy - SAKK 38/08. Br J Haematol. 2016 Jul;174(2):255-63. Epub 2016 Mar 28. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.14049/abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27018242 PubMed]
+#Hitz F, Zucca E, Pabst T, Fischer N, Cairoli A, Samaras P, Caspar CB, Mach N, Krasniqi F, Schmidt A, Rothermundt C, Enoiu M, Eckhardt K, Berardi Vilei S, Rondeau S, Mey U. Rituximab, bendamustine and lenalidomide in patients with aggressive B-cell lymphoma not eligible for anthracycline-based therapy or intensive salvage chemotherapy - SAKK 38/08. Br J Haematol. 2016 Jul;174(2):255-63. Epub 2016 Mar 28. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.14049/abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27018242 PubMed]
 ==R-CVEP {{#subobject:cea36|Regimen=1}}==
@@ Line 4,685: / Line 5,089: @@
 ===Regimen {{#subobject:d9b3c|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/bjh.13195/full Straus et al. 2014 (MSK 08-045)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 4,695: / Line 5,099: @@
 ''The MTD for vorinostat was 300 mg in this phase I/II trial.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once per day on days 1 & 8
@@ Line 4,704: / Line 5,109: @@
 ===References===
-# '''MSK 08-045:''' Straus DJ, Hamlin PA, Matasar MJ, Lia Palomba M, Drullinsky PR, Zelenetz AD, Gerecitano JF, Noy A, Hamilton AM, Elstrom R, Wegner B, Wortman K, Cella D. Phase I/II trial of vorinostat with rituximab, cyclophosphamide, etoposide and prednisone as palliative treatment for elderly patients with relapsed or refractory diffuse large B-cell lymphoma not eligible for autologous stem cell transplantation. Br J Haematol. 2015 Mar;168(5):663-70. Epub 2014 Oct 15. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13195/full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25316653 PubMed]
+#'''MSK 08-045:''' Straus DJ, Hamlin PA, Matasar MJ, Lia Palomba M, Drullinsky PR, Zelenetz AD, Gerecitano JF, Noy A, Hamilton AM, Elstrom R, Wegner B, Wortman K, Cella D. Phase I/II trial of vorinostat with rituximab, cyclophosphamide, etoposide and prednisone as palliative treatment for elderly patients with relapsed or refractory diffuse large B-cell lymphoma not eligible for autologous stem cell transplantation. Br J Haematol. 2015 Mar;168(5):663-70. Epub 2014 Oct 15. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13195/full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25316653 PubMed]
 ==R-GemOx {{#subobject:bb9813|Regimen=1}}==
@@ Line 4,715: / Line 5,121: @@
 ===Regimen variant #1, 14-day cycles {{#subobject:a875bf|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://annonc.oxfordjournals.org/content/18/8/1363.long El Gnaoui et al. 2007]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3815173/ Mounier et al. 2013]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV at fixed dose rate over 100 minutes once on day 2
@@ Line 4,731: / Line 5,138: @@
 ====Supportive medications====
 *[[Methylprednisolone (Solumedrol)]] 1 mg/kg IV once on day 1, prior to [[Rituximab (Rituxan)]]
 *[[Acetaminophen (Tylenol)]] 1000 mg PO once on day 1, prior to [[Rituximab (Rituxan)]]
@@ Line 4,740: / Line 5,148: @@
 ===Regimen variant #2, 21-day cycles {{#subobject:b976d9|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/j.1600-0609.2007.00996.x/full López et al. 2008]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once on day 1
@@ Line 4,754: / Line 5,163: @@
 '''21-day cycle for 6 to 8 cycles'''
 ===References===
-# El Gnaoui T, Dupuis J, Belhadj K, Jais JP, Rahmouni A, Copie-Bergman C, Gaillard I, Diviné M, Tabah-Fisch I, Reyes F, Haioun C. Rituximab, gemcitabine and oxaliplatin: an effective salvage regimen for patients with relapsed or refractory B-cell lymphoma not candidates for high-dose therapy. Ann Oncol. 2007 Aug;18(8):1363-8. Epub 2007 May 11. [http://annonc.oxfordjournals.org/content/18/8/1363.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17496309 PubMed]
-# López A, Gutiérrez A, Palacios A, Blancas I, Navarrete M, Morey M, Perelló A, Alarcón J, Martínez J, Rodríguez J. GEMOX-R regimen is a highly effective salvage regimen in patients with refractory/relapsing diffuse large-cell lymphoma: a phase II study. Eur J Haematol. 2008 Feb;80(2):127-32. Epub 2007 Nov 20. [https://onlinelibrary.wiley.com/doi/10.1111/j.1600-0609.2007.00996.x/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18005385 PubMed]
+#El Gnaoui T, Dupuis J, Belhadj K, Jais JP, Rahmouni A, Copie-Bergman C, Gaillard I, Diviné M, Tabah-Fisch I, Reyes F, Haioun C. Rituximab, gemcitabine and oxaliplatin: an effective salvage regimen for patients with relapsed or refractory B-cell lymphoma not candidates for high-dose therapy. Ann Oncol. 2007 Aug;18(8):1363-8. Epub 2007 May 11. [http://annonc.oxfordjournals.org/content/18/8/1363.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17496309 PubMed]
-# Mounier N, El-Gnaoui T, Tilly H, Canioni D, Sebban C, Casasnovas RO, Delarue R, Sonet A, Beaussart P, Petrella T, Castaigne S, Bologna S, Salles G, Rahmouni A, Gaulard P, Haioun C. Rituximab plus gemcitabine and oxaliplatin in refractory/relapsed patients with diffuse large B-cell lymphoma who are not candidates for high-dose therapy: a phase II Lymphoma Study Association trial. Haematologica. 2013 Nov;98(11):1726-31. Epub 2013 Jun 10. [http://www.haematologica.org/content/98/11/1726.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3815173/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23753028 PubMed]
+#López A, Gutiérrez A, Palacios A, Blancas I, Navarrete M, Morey M, Perelló A, Alarcón J, Martínez J, Rodríguez J. GEMOX-R regimen is a highly effective salvage regimen in patients with refractory/relapsing diffuse large-cell lymphoma: a phase II study. Eur J Haematol. 2008 Feb;80(2):127-32. Epub 2007 Nov 20. [https://onlinelibrary.wiley.com/doi/10.1111/j.1600-0609.2007.00996.x/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18005385 PubMed]
+#Mounier N, El-Gnaoui T, Tilly H, Canioni D, Sebban C, Casasnovas RO, Delarue R, Sonet A, Beaussart P, Petrella T, Castaigne S, Bologna S, Salles G, Rahmouni A, Gaulard P, Haioun C. Rituximab plus gemcitabine and oxaliplatin in refractory/relapsed patients with diffuse large B-cell lymphoma who are not candidates for high-dose therapy: a phase II Lymphoma Study Association trial. Haematologica. 2013 Nov;98(11):1726-31. Epub 2013 Jun 10. [http://www.haematologica.org/content/98/11/1726.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3815173/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23753028 PubMed]
 ==Temsirolimus monotherapy {{#subobject:4baa29|Regimen=1}}==
@@ Line 4,765: / Line 5,175: @@
 ===Regimen {{#subobject:21e303|Variant=1}}===
 {| class="wikitable" style="width: 75%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 33%" |Study
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
+! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020703/ Smith et al. 2010]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 | style="background-color:#8c6bb1" |ORR: 28%
 |-
 |}
 ====Chemotherapy====
 *[[Temsirolimus (Torisel)]] 25 mg IV over 30 minutes once per day on days 1, 8, 15, 22
@@ Line 4,780: / Line 5,191: @@
 ===References===
-# Smith SM, van Besien K, Karrison T, Dancey J, McLaughlin P, Younes A, Smith S, Stiff P, Lester E, Modi S, Doyle LA, Vokes EE, Pro B. Temsirolimus has activity in non-mantle cell non-Hodgkin's lymphoma subtypes: The University of Chicago phase II consortium. J Clin Oncol. 2010 Nov 1;28(31):4740-6. Epub 2010 Sep 13. [http://jco.ascopubs.org/content/28/31/4740.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020703/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20837940 PubMed]
+#Smith SM, van Besien K, Karrison T, Dancey J, McLaughlin P, Younes A, Smith S, Stiff P, Lester E, Modi S, Doyle LA, Vokes EE, Pro B. Temsirolimus has activity in non-mantle cell non-Hodgkin's lymphoma subtypes: The University of Chicago phase II consortium. J Clin Oncol. 2010 Nov 1;28(31):4740-6. Epub 2010 Sep 13. [http://jco.ascopubs.org/content/28/31/4740.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020703/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20837940 PubMed]
 ==Tisagenlecleucel monotherapy {{#subobject:d68f14|Regimen=1}}==
@@ Line 4,793: / Line 5,205: @@
 |}
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|Years of enrollment
+! style="width: 25%" |Years of enrollment
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788566/ Schuster et al. 2017 (UPCC 13413)]
 |{{#subobject:xx|ToDo=1}}
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |
 |-
 |[https://www.nejm.org/doi/full/10.1056/NEJMoa1804980 Schuster et al. 2018 (JULIET)]
 |2015-2017
-|style="background-color:#91cf61"|Phase II (RT)
+| style="background-color:#91cf61" |Phase II (RT)
 | style="background-color:#9ebcda" |ORR: 59% (95% CI, 44-72)
 |-
@@ Line 4,811: / Line 5,223: @@
 ''The range given is the FDA-recommended dose used in JULIET.''
 ====Preceding treatment====
 *Lymphodepleting therapy with [[Autologous_HSCT#FC|FC]] or [[Autologous_HSCT#Bendamustine_monotherapy|Bendamustine]]
 ====Immunotherapy====
 *[[Tisagenlecleucel (Kymriah)]] 0.6 to 6 x 10<sup>8</sup> CTL019 transduced viable T-cells IV once on day 0
@@ Line 4,819: / Line 5,233: @@
 ===References===
-# '''UPCC 13413:''' Schuster SJ, Svoboda J, Chong EA, Nasta SD, Mato AR, Anak Ö, Brogdon JL, Pruteanu-Malinici I, Bhoj V, Landsburg D, Wasik M, Levine BL, Lacey SF, Melenhorst JJ, Porter DL, June CH. Chimeric Antigen Receptor T Cells in Refractory B-Cell Lymphomas. N Engl J Med. 2017 Dec 28;377(26):2545-2554. Epub 2017 Dec 10. [https://www.nejm.org/doi/10.1056/NEJMoa1708566 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788566/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29226764 PubMed]
+#'''UPCC 13413:''' Schuster SJ, Svoboda J, Chong EA, Nasta SD, Mato AR, Anak Ö, Brogdon JL, Pruteanu-Malinici I, Bhoj V, Landsburg D, Wasik M, Levine BL, Lacey SF, Melenhorst JJ, Porter DL, June CH. Chimeric Antigen Receptor T Cells in Refractory B-Cell Lymphomas. N Engl J Med. 2017 Dec 28;377(26):2545-2554. Epub 2017 Dec 10. [https://www.nejm.org/doi/10.1056/NEJMoa1708566 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788566/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29226764 PubMed]
 <!-- # '''Abstract:''' Schuster SJ, Bishop MR, Tam C, et al. Global Pivotal Phase 2 Trial of the CD19-Targeted Therapy CTL019 in Adult Patients with Relapsed or Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)—an Interim Analysis. Hematological Oncology. 2017;35(S2):27. [https://onlinelibrary.wiley.com/doi/full/10.1002/hon.2437_6 link to abstract] -->
-# '''JULIET:''' Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, Jäger U, Jaglowski S, Andreadis C, Westin JR, Fleury I, Bachanova V, Foley SR, Ho PJ, Mielke S, Magenau JM, Holte H, Pantano S, Pacaud LB, Awasthi R, Chu J, Anak Ö, Salles G, Maziarz RT; JULIET Investigators. Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N Engl J Med. 2019 Jan 3;380(1):45-56. Epub 2018 Dec 1.  [https://www.nejm.org/doi/full/10.1056/NEJMoa1804980 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30501490 PubMed]
+#'''JULIET:''' Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, Jäger U, Jaglowski S, Andreadis C, Westin JR, Fleury I, Bachanova V, Foley SR, Ho PJ, Mielke S, Magenau JM, Holte H, Pantano S, Pacaud LB, Awasthi R, Chu J, Anak Ö, Salles G, Maziarz RT; JULIET Investigators. Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N Engl J Med. 2019 Jan 3;380(1):45-56. Epub 2018 Dec 1.  [https://www.nejm.org/doi/full/10.1056/NEJMoa1804980 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30501490 PubMed]
 ==TTR {{#subobject:934c01|Regimen=1}}==
@@ Line 4,832: / Line 5,247: @@
 ===Regimen {{#subobject:4882ef|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5279071/ Westin et al. 2014]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Chemotherapy====
 *[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV once on day 2
 *[[Topotecan (Hycamtin)]] 1 mg/m<sup>2</sup> IV once per day on days 2 to 6
@@ Line 4,845: / Line 5,261: @@
 ====Supportive medications====
 *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day from day 7 until neutrophil recovery
 *[[Dexamethasone (Decadron)]] 20 mg IV once on day 2; 30 minutes prior to [[Paclitaxel (Taxol)]]
@@ Line 4,852: / Line 5,269: @@
 ===References===
-# Westin JR, McLaughlin P, Romaguera J, Hagemeister FB, Pro B, Dang NH, Samaniego F, Rodriguez MA, Fayad L, Oki Y, Fanale M, Fowler N, Nastoupil L, Feng L, Loyer E, Younes A. Paclitaxel, topotecan and rituximab: long term outcomes of an effective salvage programme for relapsed or refractory aggressive B-cell non-Hodgkin lymphoma. Br J Haematol. 2014 Oct;167(2):177-84. Epub 2014 Jul 8. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13014/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5279071/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25039868 PubMed]
+#Westin JR, McLaughlin P, Romaguera J, Hagemeister FB, Pro B, Dang NH, Samaniego F, Rodriguez MA, Fayad L, Oki Y, Fanale M, Fowler N, Nastoupil L, Feng L, Loyer E, Younes A. Paclitaxel, topotecan and rituximab: long term outcomes of an effective salvage programme for relapsed or refractory aggressive B-cell non-Hodgkin lymphoma. Br J Haematol. 2014 Oct;167(2):177-84. Epub 2014 Jul 8. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13014/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5279071/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25039868 PubMed]
 ==Vinorelbine monotherapy {{#subobject:29c647|Regimen=1}}==
@@ Line 4,862: / Line 5,280: @@
 ===Regimen {{#subobject:f0bd7f|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://annonc.oxfordjournals.org/content/7/9/970.long Balzarotti et al. 1996]
-|style="background-color:#ffffbe"|Non-randomized, <20 pts in this subgroup
+| style="background-color:#ffffbe" |Non-randomized, <20 pts in this subgroup
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70212-7/fulltext Pettengell et al. 2012 (PIX301)]
-|style="background-color:#91cf61"|Phase III, <20 pts in this arm (C)
+| style="background-color:#91cf61" |Phase III, <20 pts in this arm (C)
 |[[#Pixantrone_monotherapy|Pixantrone]]
-|style="background-color:#fc8d59"|Seems to have inferior CR/CRu rate
+| style="background-color:#fc8d59" |Seems to have inferior CR/CRu rate
 |-
 |}
 ''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.''
 ====Chemotherapy====
 *[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
@@ Line 4,885: / Line 5,304: @@
 ===References===
-# Balzarotti M, Santoro A, Tondini C, Fornier M, Bonadonna G. Activity of single agent vinorelbine in pretreated non-Hodgkin's lymphoma. Ann Oncol. 1996 Nov;7(9):970-2. [http://annonc.oxfordjournals.org/content/7/9/970.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9006750 PubMed]
-# '''Review:''' Webb MS, Saltman DL, Connors JM, Goldie JH. A literature review of single agent treatment of multiply relapsed aggressive non-Hodgkin's lymphoma. Leuk Lymphoma. 2002 May;43(5):975-82.  [https://www.tandfonline.com/doi/full/10.1080/10428190290021632 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12148908 PubMed]
+#Balzarotti M, Santoro A, Tondini C, Fornier M, Bonadonna G. Activity of single agent vinorelbine in pretreated non-Hodgkin's lymphoma. Ann Oncol. 1996 Nov;7(9):970-2. [http://annonc.oxfordjournals.org/content/7/9/970.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9006750 PubMed]
-# '''PIX301:''' Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70212-7/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22652183 PubMed]
+#'''Review:''' Webb MS, Saltman DL, Connors JM, Goldie JH. A literature review of single agent treatment of multiply relapsed aggressive non-Hodgkin's lymphoma. Leuk Lymphoma. 2002 May;43(5):975-82.  [https://www.tandfonline.com/doi/full/10.1080/10428190290021632 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12148908 PubMed]
-## '''Post-hoc analysis:''' Pettengell R, Sebban C, Zinzani PL, Derigs HG, Kravchenko S, Singer JW, Theocharous P, Wang L, Pavlyuk M, Makhloufi KM, Coiffier B. Monotherapy with pixantrone in histologically confirmed relapsed or refractory aggressive B-cell non-Hodgkin lymphoma: post-hoc analyses from a phase III trial. Br J Haematol. 2016 Sep;174(5):692-9. Epub 2016 Apr 26. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.14101/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5074333/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27118109 PubMed]
+#'''PIX301:''' Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70212-7/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22652183 PubMed]
+##'''Post-hoc analysis:''' Pettengell R, Sebban C, Zinzani PL, Derigs HG, Kravchenko S, Singer JW, Theocharous P, Wang L, Pavlyuk M, Makhloufi KM, Coiffier B. Monotherapy with pixantrone in histologically confirmed relapsed or refractory aggressive B-cell non-Hodgkin lymphoma: post-hoc analyses from a phase III trial. Br J Haematol. 2016 Sep;174(5):692-9. Epub 2016 Apr 26. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.14101/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5074333/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27118109 PubMed]
 =Maintenance after further lines of therapy=
@@ Line 4,898: / Line 5,318: @@
 ===Regimen {{#subobject:829190|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(11)00023-1/abstract Zinzani et al. 2011a]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Preceding treatment====
 *[[#Lenalidomide_.26_Rituximab|Lenalidomide & Rituximab]] x 4
 ====Chemotherapy====
 *[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 1 to 21
@@ Line 4,913: / Line 5,336: @@
 ===References===
-# Zinzani PL, Pellegrini C, Gandolfi L, Stefoni V, Quirini F, Derenzini E, Broccoli A, Argnani L, Pileri S, Baccarani M. Combination of lenalidomide and rituximab in elderly patients with relapsed or refractory diffuse large B-cell lymphoma: a phase 2 trial. Clin Lymphoma Myeloma Leuk. 2011 Dec;11(6):462-6. Epub 2011 May 4. [http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(11)00023-1/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21859554 PubMed]
-## '''Update:''' Zinzani PL, Pellegrini C, Derenzini E, Argnani L, Pileri S. Long-term efficacy of the combination of lenalidomide and rituximab in elderly relapsed/refractory diffuse large B-cell lymphoma patients. Hematol Oncol. 2013 Dec;31(4):223-4. Epub 2013 Apr 26. [https://onlinelibrary.wiley.com/doi/10.1002/hon.2049/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23620452 PubMed]
+#Zinzani PL, Pellegrini C, Gandolfi L, Stefoni V, Quirini F, Derenzini E, Broccoli A, Argnani L, Pileri S, Baccarani M. Combination of lenalidomide and rituximab in elderly patients with relapsed or refractory diffuse large B-cell lymphoma: a phase 2 trial. Clin Lymphoma Myeloma Leuk. 2011 Dec;11(6):462-6. Epub 2011 May 4. [http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(11)00023-1/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21859554 PubMed]
+##'''Update:''' Zinzani PL, Pellegrini C, Derenzini E, Argnani L, Pileri S. Long-term efficacy of the combination of lenalidomide and rituximab in elderly relapsed/refractory diffuse large B-cell lymphoma patients. Hematol Oncol. 2013 Dec;31(4):223-4. Epub 2013 Apr 26. [https://onlinelibrary.wiley.com/doi/10.1002/hon.2049/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23620452 PubMed]
 =Response criteria=
 *[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979083/ Lugano Classification criteria (2014)] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979083/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25113753 PubMed]
 *[http://jco.ascopubs.org/content/25/5/579.long International Harmonization Project on Lymphoma revised criteria (2007)] [https://www.ncbi.nlm.nih.gov/pubmed/17242396 PubMed]
@@ Line 4,929: / Line 5,354: @@
 |}
 To be completed
-# A predictive model for aggressive non-Hodgkin's lymphoma. The International Non-Hodgkin's Lymphoma Prognostic Factors Project. N Engl J Med. 1993 Sep 30;329(14):987-94. [https://www.nejm.org/doi/full/10.1056/NEJM199309303291402 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8141877 PubMed]
+#A predictive model for aggressive non-Hodgkin's lymphoma. The International Non-Hodgkin's Lymphoma Prognostic Factors Project. N Engl J Med. 1993 Sep 30;329(14):987-94. [https://www.nejm.org/doi/full/10.1056/NEJM199309303291402 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8141877 PubMed]
 ==Revised International Prognostic Index, R-IPI (2007)==
@@ Line 4,937: / Line 5,363: @@
 |}
 To be completed
-# Sehn LH, Berry B, Chhanabhai M, Fitzgerald C, Gill K, Hoskins P, Klasa R, Savage KJ, Shenkier T, Sutherland J, Gascoyne RD, Connors JM. The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood. 2007 Mar 1;109(5):1857-61. Epub 2006 Nov 14. [http://www.bloodjournal.org/content/109/5/1857.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17105812 PubMed]
+#Sehn LH, Berry B, Chhanabhai M, Fitzgerald C, Gill K, Hoskins P, Klasa R, Savage KJ, Shenkier T, Sutherland J, Gascoyne RD, Connors JM. The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood. 2007 Mar 1;109(5):1857-61. Epub 2006 Nov 14. [http://www.bloodjournal.org/content/109/5/1857.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17105812 PubMed]
 ==CNS-IPI (2016)==
@@ Line 4,945: / Line 5,372: @@
 |}
 ===Risk factors===
 *Age greater than 60 years
 *Elevated LDH
@@ Line 4,951: / Line 5,379: @@
 *Involvement of more than one extranodal site
 *Involvement of the kidney and/or adrenal glands
 ===Risk stratification===
 *'''Low risk:''' 0 or 1 risk factors (''2-year rate of CNS disease less than 5%'')
 *'''Intermediate risk:''' 2 or 3 risk factors (''2-year rate of CNS disease less than 5%'')
 *'''High risk:''' 4 to 6 risk factors (''2-year rate of CNS disease greater than 10%'')
 ===References===
-# Schmitz N, Zeynalova S, Nickelsen M, Kansara R, Villa D, Sehn LH, Glass B, Scott DW, Gascoyne RD, Connors JM, Ziepert M, Pfreundschuh M, Loeffler M, Savage KJ. CNS International Prognostic Index: a risk model for CNS relapse in patients with diffuse large B-cell lymphoma treated with R-CHOP. J Clin Oncol. 2016 Sep 10;34(26):3150-3156. Epub 2016 Jul 5. [http://jco.ascopubs.org/content/34/26/3150.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27382100 PubMed]
+#Schmitz N, Zeynalova S, Nickelsen M, Kansara R, Villa D, Sehn LH, Glass B, Scott DW, Gascoyne RD, Connors JM, Ziepert M, Pfreundschuh M, Loeffler M, Savage KJ. CNS International Prognostic Index: a risk model for CNS relapse in patients with diffuse large B-cell lymphoma treated with R-CHOP. J Clin Oncol. 2016 Sep 10;34(26):3150-3156. Epub 2016 Jul 5. [http://jco.ascopubs.org/content/34/26/3150.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27382100 PubMed]
 =Investigational agents=

Difference between revisions of "Diffuse large B-cell lymphoma"

Revision as of 17:20, 30 January 2020

Guidelines

ESMO

Older

NCCN

Untreated, pre-phase

Vincristine & Prednisone

Regimen variant #1, PO vincristine

Chemotherapy

Subsequent treatment

Regimen variant #2, IV vincristine

Chemotherapy

Subsequent treatment

References

Untreated, randomized data

ACVBP-R

Regimen

Chemotherapy

CNS prophylaxis

Supportive medications

Subsequent treatment

References

DA-R-EPOCH

Regimen

Chemotherapy

Supportive medications

Dose modifications

References

R-CHOEP-14

Regimen variant #1, flat-dose vincristine

Chemotherapy

Subsequent treatment

Regimen variant #2, capped vincristine, with CNS prophylaxis

Chemotherapy

Supportive medications

Subsequent treatment

References

R-CHOP

Example orders

Regimen variant #1, prednisone 40 mg/m2

Chemotherapy

Supportive medications

CNS prophylaxis

Regimen variant #2, prednisone 60 mg/m2

Chemotherapy

Regimen variant #3, prednisone 100 mg, capped vincristine, 4 cycles

Chemotherapy

Regimen variant #4, prednisone 100 mg, capped vincristine, 6 cycles

Chemotherapy

Supportive medications

Subsequent treatment

Regimen variant #5, prednisone 100 mg, flat-dose vincristine

Chemotherapy

Supportive medications

Subsequent treatment

Regimen variant #6, prednisone 100 mg/m2

Chemotherapy

Regimen variant #7, rituximab lead-in

Chemotherapy

Supportive medications

Subsequent treatment

Regimen variant #8, short-course for early stage DLBCL

Preceding treatment

Chemotherapy

Subsequent treatment

Regimen variant #9, primary testicular DLBCL

Preceding treatment

Chemotherapy

CNS prophylaxis

Subsequent treatent

Regimen variant #10, 2 cycles with response adaptation

Chemotherapy

Subsequent treatment

References

R-CHOP (Prednisolone)

Example orders

Regimen variant #1, prednisolone 40 mg/m2

Chemotherapy

CNS prophylaxis

Regimen variant #1, prednisone 40 mg/m²

Regimen variant #2, prednisone 60 mg/m²

Regimen variant #6, prednisone 100 mg/m²

Regimen variant #1, prednisolone 40 mg/m²

Regimen variant #4, prednisolone 100 mg/m²

Regimen variant #1, prednisone 40 mg/m², 4 to 6 cycles

Regimen variant #2, prednisone 40 mg/m², 8 cycles