Revision as of 02:37, 9 October 2016

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109 regimens on this page 165 variants on this page

Untreated, pre-phase

Vincristine & Prednisone

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Regimen

Study	Evidence
Pfreundschuh et al. 2004 (NHL-B1)	Non-randomized portion of RCT
Pfreundschuh et al. 2004 (NHL-B2)	Non-randomized
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

Treatment in NHL-B1 and NHL-B2 followed by randomization to CHOP versus CHOP-14 versus CHOEP versus CHOEP-14. Treatment in RICOVER-60 followed by randomization to CHOP-14 versus R-CHOP-14. Treatment in SMARTE-R-CHOP-14 followed by R-CHOP-14.

References

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
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
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
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

Untreated, randomized data

ACVBP-R

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

Synonyms: R-ACVBP

Structured Concept: none

Regimen

Study	Evidence	Comparator	Efficacy	Toxicity
Récher et al. 2011 (LNH03-2B)	Phase III	R-CHOP	Superior OS	Increased toxicity
Ketterer et al. 2013 (LNH03-1B)	Phase III	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 intrathecal on day 1

Supportive medications

Filgrastim (Neupogen) 300 mcg (for patients <75 kg) or 480 mcg (for patients ≥75 kg) SC once per day on days 6 to 13

14-day cycle for 4 cycles

Treatment followed in 4 weeks by methotrexate consolidation.

References

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
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

CHOP

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CHOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

Synonyms: CHOP-21, ACOP, CAVP, COPA, VACP, VCAP

Structured Concept: C9549 (NCI-T), C0055598 (NCI-MT/UMLS)

Regimen #1

Study	Evidence	Comparator
Elias et al. 1978	Non-randomized
Fisher et al. 1993 (SWOG-8516/Intergroup 0067)	Phase III	MACOP-B m-BACOD ProMACE-CytaBOM
Miller et al. 1998 (SWOG S8736)	Phase III	CHOP x 3 -> RT

Chemotherapy

Cyclophosphamide (Cytoxan) 750 mg/m² IV over 15 minutes once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV bolus over 1 to 2 minutes once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg per cycle) IV bolus over 1 to 2 minutes once on day 1
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

21-day cycle for 8 cycles

Regimen #2

Study	Evidence	Comparator
Pfreundschuh et al. 2004 (NHL-B1)	Phase III	CHOEP-14 CHOEP-21 CHOP-14
Pfreundschuh et al. 2004 (NHL-B2)	Phase III	CHOEP-14 CHOEP-21 CHOP-14
Verdonck et al. 2007	Phase III	I-CHOP

Treatment in NHL-B1 and NHL-B2 preceded by pre-phase vincristine & prednisone.

Chemotherapy

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

Per NHL-B1 and NHL-B2: At the discretion of ordering physician: Filgrastim (Neupogen) 300 mcg (for patients <75 kg) or 480 mcg (for patients at least 75 kg) SC once per day on days 4 to 13

21-day cycle for 6 cycles

Radiation therapy for initial bulky disease (NHL-B2)

"Initial bulky disease": patients with "lymphoma masses or conglomerates with a diameter ≥7.5 cm) or extranodal involvement"

Radiation therapy, 36 Gy to areas of initial bulky disease

Regimen #3, CHOP x 3 -> XRT

Study	Evidence	Comparator
Miller et al. 1998 (SWOG S8736)	Phase III	CHOP x 8
Reyes et al. 2005	Phase III	ACVBP

Chemotherapy

Cyclophosphamide (Cytoxan) 750 mg/m² IV over 15 minutes once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV bolus over 1 to 2 minutes once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg per cycle) IV bolus over 1 to 2 minutes once on day 1
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

21-day cycle for 3 cycles, followed in 3 weeks by:

Radiotherapy

Involved field radiation therapy, 180 to 200 cGy fractions, total dose of 4000 to 5500 cGy. Total dose was often influenced by whether patients had clinical evidence of residual disease after 4000 cGy.

Regimen #4

Study	Evidence	Comparator
Coiffier et al. 2002 (LNH-98.5)	Phase III	R-CHOP
Tilly et al. 2003	Phase III	ACVBP

Chemotherapy

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 per cycle) 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

Regimen #5

Study	Evidence	Comparator	Efficacy
Habermann et al. 2006 (CALGB 9793)	Phase III	R-CHOP	Might have inferior FFS

Chemotherapy

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 per cycle: 2 mg) IV once on day 1
Prednisone (Sterapred) 100 mg/m² PO once per day on days 1 to 5

Supportive medications

Filgrastim (Neupogen) "recommended according to guidelines"

21-day cycle for 6 to 8 cycles

Patients with CR/PR proceeded to receive maintenance rituximab versus observation.

References

McKelvey EM, Gottlieb JA, Wilson HE, Haut A, Talley RW, Stephens R, Lane M, Gamble JF, Jones SE, Grozea PN, Gutterman J, Coltman C, Moon TE. Hydroxyldaunomycin (Adriamycin) combination chemotherapy in malignant lymphoma. Cancer. 1976 Oct;38(4):1484-93. PubMed
Elias L, Portlock CS, Rosenberg SA. Combination chemotherapy of diffuse histiocytic lymphoma with cyclophosphamide, adriamycin, vincristine and prednisone (CHOP). Cancer. 1978 Oct;42(4):1705-10. link to original article contains verified protocol PubMed
Pavlovsky S, Santarelli MT, Erazo A, Diaz Maqueo JC, Somoza N, Lluesma Goñalons M, Cervantes G, Garcia Vela EL, Corrado C, Magnasco H, et al. Results of a randomized study of previously-untreated intermediate and high grade lymphoma using CHOP versus CNOP. Ann Oncol. 1992 Mar;3(3):205-9. link to original article PubMed
Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med. 1993 Apr 8;328(14):1002-6. link to original article PubMed
1. Update: Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP. A phase III comparison of CHOP vs. m-BACOD vs. ProMACE-CytaBOM vs. MACOP-B in patients with intermediate- or high-grade non-Hodgkin's lymphoma: results of SWOG-8516 (Intergroup 0067), the National High-Priority Lymphoma Study. Ann Oncol. 1994;5 Suppl 2:91-5. PubMed
2. Update: Bernstein SH, Unger JM, Leblanc M, Friedberg J, Miller TP, Fisher RI. Natural history of CNS relapse in patients with aggressive non-Hodgkin's lymphoma: a 20-year follow-up analysis of SWOG 8516 -- the Southwest Oncology Group. J Clin Oncol. 2009 Jan 1;27(1):114-9. Epub 2008 Dec 1. link to original article PubMed
Tondini C, Zanini M, Lombardi F, Bengala C, Rocca A, Giardini R, Buzzoni R, Valagussa P, Bonadonna G. Combined modality treatment with primary CHOP chemotherapy followed by locoregional irradiation in stage I or II histologically aggressive non-Hodgkin's lymphomas. J Clin Oncol. 1993 Apr;11(4):720-5. link to original article PubMed
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 PubMed
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 PubMed
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
Tilly H, Lepage E, Coiffier B, Blanc M, Herbrecht R, Bosly A, Attal M, Fillet G, Guettier C, Molina TJ, Gisselbrecht C, Reyes F; Groupe d'Etude des Lymphomes de l'Adulte. Intensive conventional chemotherapy (ACVBP regimen) compared with standard CHOP for poor-prognosis aggressive non-Hodgkin lymphoma. Blood. 2003 Dec 15;102(13):4284-9. Epub 2003 Aug 14. link to original article contains verified protocol PubMed
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
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
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
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
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
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 protocol PubMed
Verdonck LF, Notenboom A, de Jong DD, MacKenzie MA, Verhoef GE, Kramer MH, Ossenkoppele GJ, Doorduijn JK, Sonneveld P, van Imhoff GW. Intensified 12-week CHOP (I-CHOP) plus G-CSF compared with standard 24-week CHOP (CHOP-21) for patients with intermediate-risk aggressive non-Hodgkin lymphoma: a phase 3 trial of the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON). Blood. 2007 Apr 1;109(7):2759-66. link to original article contains verified protocol PubMed

CHOP Intensified

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CHOP-DI: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone, Dose Intense
I-CHOP: Intensified Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

Synonyms: CHOP-14, CHOP-DI, I-CHOP

Structured Concept: none

Regimen #1

Study	Evidence
Blayney et al. 2003 (CHOP-DI, SWOG 9349)	Phase II

Chemotherapy

Cyclophosphamide (Cytoxan) 1600 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) 100 mg PO once per day on days 1 to 5

Supportive medications

Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 2 to 11, or until ANC is greater than 10,000

14-day cycle for up to 6 cycles

Regimen #2

Study	Evidence	Comparator
Verdonck et al. 2007	Phase III	CHOP

Chemotherapy

Cyclophosphamide (Cytoxan) 1000 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 70 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

Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 2 to 11

14-day cycle for 6 cycles

Regimen #3

Study	Evidence	Comparator
Pfreundschuh et al. 2004 (NHL-B1)	Phase III	CHOEP-14 CHOEP-21 CHOP
Pfreundschuh et al. 2008 (RICOVER-60)	Phase III	R-CHOP-14

Treatment preceded by pre-phase vincristine & prednisone (recommended in NHL-B1 and mandatory in RICOVER-60).

Chemotherapy

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 (per Pfreundschuh et al. 2004):

Filgrastim (Neupogen) 300 mcg (for patients <75 kg) or 480 mcg (for patients at least 75 kg) SC once per day on days 4 to 13

14-day cycle for 6 cycles; some patients in Pfreundschuh et al. 2008 received 14-day cycle for 8 cycles

Radiation therapy for initial bulky disease

"Initial bulky disease": patients with "lymphoma masses or conglomerates with a diameter =7.5 cm) or extranodal involvement"

Radiation therapy, 36 Gy to areas of initial bulky disease

References

Blayney DW, LeBlanc ML, Grogan T, Gaynor ER, Chapman RA, Spiridonidis CH, Taylor SA, Bearman SI, Miller TP, Fisher RI; Southwest Oncology Group. Dose-intense chemotherapy every 2 weeks with dose-intense cyclophosphamide, doxorubicin, vincristine, and prednisone may improve survival in intermediate- and high-grade lymphoma: a phase II study of the Southwest Oncology Group (SWOG 9349). J Clin Oncol. 2003 Jul 1;21(13):2466-73. link to original article contains verified protocol PubMed
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
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
Verdonck LF, Notenboom A, de Jong DD, MacKenzie MA, Verhoef GE, Kramer MH, Ossenkoppele GJ, Doorduijn JK, Sonneveld P, van Imhoff GW. Intensified 12-week CHOP (I-CHOP) plus G-CSF compared with standard 24-week CHOP (CHOP-21) for patients with intermediate-risk aggressive non-Hodgkin lymphoma: a phase 3 trial of the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON). Blood. 2007 Apr 1;109(7):2759-66. link to original article contains verified protocol PubMed
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

CHOP Modified

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CHOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

Regimen

Study	Evidence	Comparator	Efficacy
Bessell et al. 2003	Phase III	MCOP	Seems not superior

This regimen is designed for elderly patients and is of lower intensity than standard CHOP.

Chemotherapy

Cyclophosphamide (Cytoxan) 600 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 30 mg/m² IV once on day 1
Vincristine (Oncovin) 1 mg IV once on day 1
Prednisolone (Millipred) 20 mg PO BID on days 1 to 5

21-day cycle for 6 cycles

References

Bessell EM, Burton A, Haynes AP, Glaholm J, Child JA, Cullen MH, Davies JM, Smith GM, Ellis IO, Jack A, Jones EL; Central Lymphoma Group UK. A randomised multicentre trial of modified CHOP versus MCOP in patients aged 65 years and over with aggressive non-Hodgkin's lymphoma. Ann Oncol. 2003 Feb;14(2):258-67. link to original article contains verified protocol PubMed

CNOP; MCOP

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CNOP: Cyclophosphamide, Novantrone (Mitoxantrone), Oncovin (Vincristine), Prednisone
MCOP: Mitoxantrone, Cyclophosphamide, Oncovin (Vincristine), Prednisone

Regimen

Study	Evidence	Comparator	Efficacy
Sonneveld et al. 1990	Phase II
Pavlovsky et al. 1992	Phase III	CHOP	Seems not superior
Bessell et al. 2003	Phase III	Modified CHOP	Seems not superior

Chemotherapy

Cyclophosphamide (Cytoxan) 600 mg/m² IV once on day 1
Mitoxantrone (Novantrone) 10 mg/m² IV once on day 1
Vincristine (Oncovin) 1 mg IV once on day 1
Prednisolone (Millipred) 20 mg PO BID on days 1 to 5

21-day cycle for 6 cycles

References

Sonneveld P, Michiels JJ. Full dose chemotherapy in elderly patients with non-Hodgkin's lymphoma: a feasibility study using a mitoxantrone containing regimen. Br J Cancer. 1990 Jul;62(1):105-8. link to original article PubMed
Pavlovsky S, Santarelli MT, Erazo A, Diaz Maqueo JC, Somoza N, Lluesma Goñalons M, Cervantes G, Garcia Vela EL, Corrado C, Magnasco H, et al. Results of a randomized study of previously-untreated intermediate and high grade lymphoma using CHOP versus CNOP. Ann Oncol. 1992 Mar;3(3):205-9. link to original article PubMed
Bessell EM, Burton A, Haynes AP, Glaholm J, Child JA, Cullen MH, Davies JM, Smith GM, Ellis IO, Jack A, Jones EL; Central Lymphoma Group UK. A randomised multicentre trial of modified CHOP versus MCOP in patients aged 65 years and over with aggressive non-Hodgkin's lymphoma. Ann Oncol. 2003 Feb;14(2):258-67. link to original article contains verified protocol PubMed

R-CHOEP-14

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

Regimen #1

Study	Evidence	Comparator	Efficacy	Toxicity
Schmitz et al. 2012 (DSHNHL 2002-1)	Phase III	R-MegaCHOEP	Seems not superior	Decreased toxicity

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 0 (cycles 1 to 4, 6, and 8)
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

Radiotherapy

36 Gy in daily fractions "mandatory" for patients with bulky disease (any mass > 7.5cm in diameter, or extranodal involvement)

Regimen #2, with CNS prophylaxis

Study	Evidence
Holte et al. 2013	Phase II

R-CHOEP portion

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

Filgrastim (Neupogen) 5 mcg/kg SC once per day from day 4 or Pegfilgrastim (Neulasta) 6 mg SC once on day 4

14-day cycle for 8 cycles, followed by:

CNS Prophylaxis

Note that IT treatment was not part of prophylaxis, except that Methotrexate (MTX) 15 mg IT was allowed at time of diagnostic LP.

HiDAC portion

Cytarabine (Cytosar) 3000 mg/m² IV BID for 2 days (4 doses)
- Dose reduced to 2000 mg/m² for patients aged 60-65 years

Followed 3 weeks later by:

HD-MTX portion

Methotrexate (MTX) 3000 mg/m² IV continuous infusion over 24 hours

Supportive medications

Folinic acid (Leucovorin) (dose/frequency not specified) starting at 36 hours

One course

Radiotherapy

"Given at the discretion of the individual centers (36–45 Gy). Indications for giving radiotherapy after the completion of chemotherapy included bulky disease (≥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."

References

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
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

Synonyms: R-CHOP-21, CHOP-R

Structured Concept: C9760 (NCI-T), C0393023 (NCI-MT/UMLS)

Example orders for R-CHOP in lymphoma

‘’Note: most of the variation between these regimen variants is in the dose or type of steroid.’’

Regimen #1, prednisolone 40 mg/m²

Study	Evidence	Comparator	Efficacy
Cunningham et al. 2013	Phase III	R-CHOP-14	Seems not superior
Fridrik et al. 2016 (AGMT NHL-14)	Phase III	R-COMP	Seems not superior

Note: Cunningham et al. 2013 states that the regimen is based on Coiffier et al. 2002, 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 per cycle) 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 480 mg (route not specified) BID on 3 days per week, taken throughout therapy, ending 2 weeks after chemotherapy is completed

21-day cycle for 8 cycles

Regimen #2, prednisone 100 mg/m²

Study	Evidence	Comparator	Efficacy
Offner et al. 2015	Randomized Phase II	VR-CAP	Seems not superior

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 per cycle) 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 #3, prednisone 40 mg/m²

Study	Evidence	Comparator	Efficacy
Coiffier et al. 2002 (LNH-98.5)	Phase III	CHOP	Superior OS
Delarue et al. 2013 (LNH03-6B)	Phase III	R-CHOP14	Seems not superior

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 per cycle) IV once on day 1
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 5

CNS prophylaxis

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

Methotrexate (MTX) 15 mg IT once every 21 days x 4 total doses

Supportive medications

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

21-day cycle for 8 cycles

Regimen #4, prednisone 100 mg, flat-dose vincristine

Study	Evidence	Comparator	Efficacy	Toxicity
Pfreundschuh et al. 2006 (MInT)	Phase III	CHOP	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

Filgrastim (Neupogen) or Lenograstim (Granocyte) used at physician discretion for neutropenia

21-day cycle for 6 cycles

Radiotherapy

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 #5, rituximab lead-in

Study	Evidence	Comparator	Efficacy
Habermann et al. 2006 (CALGB 9793)	Phase III	CHOP	Might have superior FFS

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 per cycle: 2 mg) IV once on day 1
Prednisone (Sterapred) 100 mg/m² PO once per day on days 1 to 5

Supportive medications

Filgrastim (Neupogen) "recommended according to guidelines"

21-day cycle for 6 to 8 cycles

This trial also included a randomization to maintenance rituximab versus observation for responders; however an advantage was only seen in the group receiving CHOP upfront, which is no longer standard of care.

Regimen #6, prednisone 100 mg

Study	Evidence	Comparator	Efficacy
Merli et al. 2012 (ANZINTER3)	Phase III	R-miniCEOP	Seems not superior

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 per cycle) IV once on day 1
Prednisone (Sterapred) 100 mg PO/IV once per day on days 1 to 5

Supportive medications

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

21-day cycle for 6 cycles

Radiotherapy

"At the end of chemotherapy, radiotherapy (RT) was scheduled for sites of previous bulky disease or partially responding sites."

Regimen #7, short-course for early stage DLBCL

Study	Evidence
Persky et al. 2008 (SWOG S0014)	Phase II

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on days -7, 1, 22, 43 (4 doses total)
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 per cycle) IV once on day 1
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

21-day cycle for 3 cycles, followed by:

Radiation therapy

Involved-field radiation therapy to begin 3 weeks after last cycle of R-CHOP, see paper for details.

Regimen #8, primary testicular DLBCL

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

This regimen is for primary testicular lymphoma. All patients had a 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 per cycle) IV once on day 1
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

CNS prophylaxis

Methotrexate (MTX) 12 mg IT once per week x 4 total doses

21-day cycle for 6 cycles (up to 8 cycles for stage II patients), followed by:

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.

References

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 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
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
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
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
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 PubMed
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
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
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 PubMed
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
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
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 PubMed
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 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
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 link to PMC article contains verified protocol PubMed
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
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 PubMed

R-CHOP Intensified

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

Synonyms: R-CHOP-14, Dose-dense rituximab-CHOP

Structured Concept: none

Regimen #1

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

Main CHOP-14 portion

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

Rituximab portion

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

Rituximab (Rituxan) 500 mg/m² IV once every two weeks

OR

Rituximab (Rituxan) 500 mg/m² IV once on days -1, 0, 3, 7, 14, 21, 28, 42

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

Regimen #2

Study	Evidence	Comparator	Efficacy
Delarue et al. 2013 (LNH03-6B)	Phase III	R-CHOP21	Seems not superior

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

CNS prophylaxis

Methotrexate (MTX) 15 mg IT once every 14 days x 4 total doses

Supportive medications

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

14-day cycle for 8 cycles

Regimen #3

Study	Evidence	Comparator	Efficacy
Cunningham et al. 2013	Phase III	R-CHOP-21	Seems not superior

Main R-CHOP-14 portion

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
Prednisolone (Millipred) 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 (Aloprim) 300 mg PO once per day during cycle 1
Co-trimoxazole 480 mg (route not specified) BID on 3 days per week, taken throughout therapy, ending 2 weeks after treatment is completed

14-day cycle for 6 cycles; then give additional doses of rituximab as described below

Additional doses of Rituximab

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

14-day cycle for 2 cycles

Regimen #4

Study	Evidence	Comparator	Efficacy
Pfreundschuh et al. 2008 (RICOVER-60)	Phase III	CHOP-14 x 6	Superior OS
Pfreundschuh et al. 2008 (RICOVER-60)	Phase III	CHOP-14 x 8 R-CHOP-14 x 8

Treatment preceded by 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

Filgrastim (Neupogen) or Lenograstim (Granocyte) (dose/route/frequency not specified) starting on day 4, to continue until count recovery

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

Patients with initial bulky disease received:

Radiotherapy

"Initial bulky disease": patients with "lymphoma masses or conglomerates with a diameter >=7.5 cm) or extranodal involvement"

Radiation therapy, 36 Gy to areas of initial bulky disease

Regimen #5

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

Treatment preceded by pre-phase vincristine & prednisone.

Chemotherapy=

Rituximab (Rituxan) 375 mg/m² IV once on days -4, 0, 10, 29, 57, 99, 155, and 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

Filgrastim (Neupogen) or Lenograstim (Granocyte) (dose/route/frequency not specified) starting on day 4, to continue until count recovery

14-day cycle for 6 cycles

Patients with initial bulky disease received:

Radiotherapy

"Initial bulky disease": patients with "lymphoma masses or conglomerates with a diameter =7.5 cm) or extranodal involvement"

Radiation therapy, 36 Gy to areas of initial bulky disease

References

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
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
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
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
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

R-CVP

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R-CVP: Rituximab, Cyclophosphamide, Vincristine, Prednisone

Structured Concept: C63473 (NCI-T), C1882520 (NCI-MT/UMLS)

Regimen

Chemotherapy

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

21-day cycle for up to 8 cycles

References

See references for CVP

R-HyperCVAD/R-MA

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R-HCVAD: Rituximab, Hyperfractionated Cyclophosphamide, Vincristine, Adriamycin (Doxorubicin), Dexamethasone
R-MA: Rituximab, Methotrexate, Ara-C (Cytarabine)

Regimen

Study	Evidence	Comparator	Efficacy
Oki et al. 2013	Phase III	R-CHOP	Seems to have increased CRR

Intended for high-risk DLBCL (IPI ≥3). The authors report "excellent outcome" in patients ≤45 years old, however patients >45 years old had "unacceptable mortality."

Part A (cycles 1, 3, 5)

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 300 mg/m² IV Q12H on days 1 to 3 (6 total doses)
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 PO/IV once per day on days 2 to 5

Supportive medications

Mesna (Mesnex) 600 mg/m²/day IV continuous infusion on days 1 to 3
Filgrastim (Neupogen) or Pegfilgrastim (Neulasta) starting 24 to 48 hours after completion of chemotherapy
Ciprofloxacin (Cipro) 500 mg PO BID 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 <0.75 × 10^9/L or platelet count <75 × 10^9/L on day 21

Next cycle to start once ANC count is ≥1 x 10^9/L and platelet count is ≥100 x 10^9/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.

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 then 800 mg/m² IV over 22 hours on day 1
Cytarabine (Cytosar) 3000 mg/m² IV over 2 hours Q12H on days 3 & 4 (4 total doses)

Supportive medications

Folinic acid (Leucovorin) (dose/timing not specified) until serum methotrexate level <0.1 µM
Sodium bicarbonate 1300 mg PO BID until methotrexate level <0.1 µM
Filgrastim (Neupogen) or Pegfilgrastim (Neulasta) starting 24 to 48 hours after completion of chemotherapy
Ciprofloxacin (Cipro) 500 mg PO BID 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 < 0.75 × 10^9/L or platelet count < 75 × 10^9/L on day 21
Cytarabine (Cytosar) reduced by 33% in subsequent B cycles if neutropenic fever occurs, grade 3/4 non-hematological toxicity, or ANC < 0.75 × 10^9/L or platelet count < 75 × 10^9/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 ≥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 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-miniCEOP

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

Regimen

Study	Evidence	Comparator	Efficacy
Merli et al. 2012 (ANZINTER3)	Phase III	R-CHOP	Seems not superior

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 PO/IV 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 <11 g/dL.

21-day cycle for 6 cycles

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

Radiation therapy

"At the end of chemotherapy, radiotherapy (RT) was scheduled for sites of previous bulky disease or partially responding sites."

References

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

CHOP -> IFRT -> Ibritumomab tiuxetan

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CHOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

Regimen

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

This regimen is intended for limited-stage aggressive B-cell NHL; the majority of patients studied had DLBCL.

Chemotherapy

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 per cycle) IV once on day 1
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

21-day cycle for 3 cycles, followed 3 weeks later by:

Radiation therapy

Involved-field radiation therapy, see paper for details.

Complete course followed in 3 to 6 weeks by:

Consolidation radioimmunotherapy

Rituximab (Rituxan) 250 mg/m² IV once on day 1, then another single dose on day 7, 8 or 9
Ibritumomab tiuxetan & Yttrium-90 (Zevalin) 0.4 mCi/kg (maximum dose of 32 mCi) IV once, given within four hours of second dose of Rituximab (Rituxan)

References

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 PubMed

DA-R-EPOCH

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

Synonyms: DA-EPOCH-R, EPOCH-R, REPOCH

Structured Concept: C63461 (NCI-T), C1882521 (NCI-MT/UMLS)

Regimen

Study	Evidence
García-Suárez et al. 2007	Phase II
Wilson et al. 2008	Phase II
Wilson et al. 2012	Phase II
Purroy et al. 2014	Phase II

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 on days 1 to 4 (total dose per cycle: 200 mg/m²)
Prednisone (Sterapred) 60 mg/m² PO BID on days 1 to 5
Vincristine (Oncovin) 0.4 mg/m²/day IV continuous infusion on days 1 to 4 (total dose per cycle: 1.6 mg/m²)
Cyclophosphamide (Cytoxan) 750 mg/m² IV once over 15 minutes on day 5
Doxorubicin (Adriamycin) 10 mg/m²/day IV continuous infusion on days 1 to 4 (total dose per cycle: 40 mg/m²)

Supportive medications

Growth factor support with one of the following:
- Filgrastim (Neupogen) 5 mcg/kg SQ once per day, starting on day 6 and continuing until ANC >5,000/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 BID 3 days per week
  - Alternative used only in García-Suárez et al. 2007: cotrimoxazole 480 mg PO BID 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 ug/kg SC when hemoglobin concentration was ≤100 g/l.

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 >500, increase etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
If nadir ANC <500 on 1 or 2 measurements, use same doses as last cycle.
If nadir ANC <500 on at least 3 measurements, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
And/or if nadir platelet count <25 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 >1,000 and platelets >100. 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 PubMed
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 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

Helicobacter pylori eradication therapy

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Regimen

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

Before 1996:

Amoxicillin 500mg PO q6h x 28 days
Metronidazole (Flagyl) 250mg PO q6h x 28 days
EITHER bismuth subcitrate 120mg PO q6h x 28 days
OR Omeprazole (Prilosec) 20mg PO BID x 28 days

After 1996:

Amoxicillin 500mg PO q6h x 14 days
Clarithromycin (Biaxin) 500mg PO BID x 14 days
Omeprazole (Prilosec) 20mg PO BID x 14 days

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; quiz 5057. Epub 2012 Mar 7. link to original article PubMed

R-BL

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R-BL: Rituximab, Bendamustine, Lenalidomide

Regimen

Study	Evidence	ORR
Hitz et al. 2016 (SAKK 38/08)	Phase II, <20 pts in subgroup	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; DRCOP

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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 #1

Study	Evidence
Oki et al. 2014	Phase II

Chemotherapy

Doxorubicin liposomal (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 per IV once on day 1
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 5

Supportive medications

Filgrastim (Neupogen) 5 μg/kg SC once per day from day 2 until ANC > 3000/μl

OR

Pegfilgrastim (Neulasta) 6 mg SC once on day 2

Dose modifications

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

21-day cycle for 6 to 8 cycles

Regimen #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
Doxorubicin liposomal (Doxil) 30 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg per cycle) 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
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 link to PMC article contains verified protocol PubMed

R-CEOP90 (Epirubicin)

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

Regimen

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 per cycle) IV once on day 2
Prednisolone (Millipred) 100 mg/day on days 2 to 6

21-day cycle for 4 cycles followed by involved field radiotherapy (30-45 Gy) of bulky disease and extranodal and residual masses for patients with stage IA or IIA disease; 6 cycles for all others

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; 100 mg/m² PO once per day on days 2 & 3
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg per cycle) 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

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
Doxorubicin liposomal (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; stage I patients with no LN > 5 cm received 3 cycles followed by local XRT

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-CHOP -> Ibritumomab tiuxetan

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

Regimen

Study	Evidence
Witzig et al. 2015 (ECOG3402)	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 per cycle) IV once on day 1
Prednisone (Sterapred) 100 mg/m² PO once per day on days 1 to 5

21-day cycle for 4 to 6 cycles, followed in 3 to 12 weeks by:

Consolidation 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

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

References

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 PubMed

R-GCVP

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

Regimen

Study	Evidence
Fields et al. 2013	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) prior to Rituximab (Rituxan)
Chlorpheniramine (Chlor-Trimeton) 10 mg IV 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

Fields PA, Townsend W, Webb A, Counsell N, Pocock C, Smith P, Jack A, El-Mehidi N, Johnson PW, Radford J, Linch DC, Cunnningham 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), Prednisone

Regimen

Study	Evidence
Pardal et al. 2014	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 once per day on days 1 to 5

Supportive medications

Pegfilgrastim (Neulasta) given after each cycle

21-day cycle for 3 cycles

Patients with a negative PET-CT after 3 cycles received another 3 cycles of R-MegaCHOP for a total of 6 cycles; others underwent intensification of treatment with R-IFE.

References

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, mini, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

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 neutrophil count was = 1.0 x 10⁹/L and platelet count was = 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) SQ on days 6 to 13 of the subsequent cycle until neutrophils were = 1.0 x 10⁹/L.

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; LR-CHOP-21

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

Regimen #1

Study	Evidence
Vitolo et al. 2014 (REAL07)	Phase II

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 per cycle) IV once on day 1
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 5

CNS prophylaxis

For "at risk" patients:
Methotrexate (MTX) 12 mg IT once on day 1 of first 4 cycles

Supportive medications

Granulocyte colony-stimulating factors (dose/duration not specified)
Low-molecular-weight heparins (dose/duration not specified)
Trimethoprim/Sulfamethoxazole (Bactrim DS) or Pentamidine (Nebupent) (dose/duration not specified)
Lamivudine (Epivir) (dose/duration not specified) for carriers of hepatitis B virus

21-day cycle for 6 cycles

Regimen #2

Study	Evidence
Nowakowski et al. 2014	Phase II

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 10
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 per cycle) 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

Regimen #3

Study	Evidence
Chiappella et al. 2013	Phase II

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Lenalidomide (Revlimid) 15 mg PO once per day on days 1 to 14
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 per cycle) IV once on day 1
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 5

Supportive medications

Granulocyte colony-stimulating factors (dose/duration not specified)
Low-molecular-weight heparins (dose/duration not specified)
Trimethoprim/Sulfamethoxazole (Bactrim DS) or Pentamidine (Nebupent)
Lamivudine (Epivir) for occult hepatitis B carriers

21-day cycle for 6 cycles

References

Nowakowski GS, LaPlant B, Habermann TM, Rivera CE, Macon WR, Inwards DJ, Micallef IN, Johnston PB, Porrata LF, Ansell SM, Klebig RR, Reeder CB, Witzig TE. Lenalidomide can be safely combined with R-CHOP (R2CHOP) in the initial chemotherapy for aggressive B-cell lymphomas: phase I study. Leukemia. 2011 Dec;25(12):1877-81. Epub 2011 Jul 1. link to original article contains verified protocol PubMed
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. link to original article contains verified protocol PubMed
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; on behalf of the 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
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

VR-CHOP

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VR-CHOP: Velcade (Bortezomib), Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

Regimen

Study	Evidence
Ruan et al. 2010	Phase II

Doses here are the phase II dose of bortezomib and the R-CHOP protocol as specified in the phase I report by Furman et al. 2010

Chemotherapy

Bortezomib (Velcade) 1.3 mg/m² (route not specified) once per day on days 1 & 4 (day 1 administered prior to R-CHOP)
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 per cycle) IV once on day 1
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

Supportive medications

"Standard" Acetaminophen (Tylenol) and Diphenhydramine (Benadryl) prior to Rituximab (Rituxan)

21-day cycle for 6 cycles

References

Ruan J, Martin P, Furman RR, Lee SM, Cheung K, Vose JM, Lacasce A, Morrison J, Elstrom R, Ely S, Chadburn A, Cesarman E, Coleman M, Leonard JP. Bortezomib plus CHOP-rituximab for previously untreated diffuse large B-cell lymphoma and mantle cell lymphoma. J Clin Oncol. 2011 Feb 20;29(6):690-7. Epub 2010 Dec 28. link to original article contains verified protocol PubMed

Consolidation and/or maintenance after upfront therapy

Autologous hematopoietic cell transplant

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Regimen

Study	Evidence	Comparator
Puvvada et al. 2016 (SWOG S9704)	Phase III	Observation

Treatment preceded by R-CHOP. The details of the preparative regimen were not disclosed in the abstract.

References

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 PubMed

Cytarabine (Cytosar)

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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

Treatment preceded by REI consolidation x 4.

Chemotherapy

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

14-day cycle for 2 cycles

References

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
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

Methotrexate (MTX)

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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

Treatment preceded by ACVBP-R 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

Treatment followed in 2 weeks by REI consolidation.

References

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
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	Efficacy
Jaeger et al. 2015 (NHL13)	Phase III	Rituximab	Seems not superior
Witzens-Harig et al. 2015 (HD2002)	Phase III	Rituximab	Inferior OS in males
Crump et al. 2016 (PRELUDE)	Phase III	Enzastaurin	Seems not superior
Puvvada et al. 2016 (SWOG S9704)	Phase III	AutoHCT

No further treatment, also variously termed "observation" and "watchful waiting". Preceded by "standard treatment" in HD2002 and R-CHOP in PRELUDE and SWOG S9704.

References

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
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
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 PubMed
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
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 May 23. [Epub ahead of print] link to original article PubMed
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 PubMed

REI

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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

Treatment preceded by 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

Treatment followed in 2 weeks by cytarabine consolidation.

References

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
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

Rituximab (Rituxan)

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Regimen #1

Study	Evidence	Comparator	Efficacy
Jaeger et al. 2015 (NHL13)	Phase III	Observation	Seems not superior

Treatment preceded by 8 infusions of rituximab (375 mg/m²) and 4 to 8 cycles of CHOP-like chemotherapy. 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.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once every 2 months

1 to 2 year course

Regimen #2

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

Preceded by "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 every 3 months

2 year course

References

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
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
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 PubMed
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/refractory, randomized data

DHAP

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

Regimen

Study	Evidence	Comparator	Efficacy
Velasquez et al. 1988	Phase II
Philip et al. 1995 (PARMA)	Phase III	DHAP x 2 -> BEAC	Seems to have inferior OS

Chemotherapy

Dexamethasone (Decadron) 40 mg IV over 15 minutes once per day on days 1 to 4
Cytarabine (Cytosar) as follows:
- Patients younger than 70: 2000 mg/m² IV over 3 hours Q12H x 2 doses on day 2 (total of 2 doses)
- Patients older than 70: 1000 mg/m² IV over 3 hours Q12H x 2 doses on day 2 (total of 2 doses)
Cisplatin (Platinol) 100 mg/m² IV continuous infusion over 24 hours on day 1

Supportive medications

Metoclopramide (Reglan) 1 mg/kg (route and frequency not indicated)
Diphenhydramine (Benadryl) 25 mg IV (frequency not indicated)

3 to 4 week cycle "according to the extent of myelosuppression"

Velasquez et al. 1988 report 6 to 10 courses, usually 4 courses beyond maximum response. The PARMA trial collected bone marrow after cycle 1 and then randomized responders (PR/CR) after cycle 2 to 4 more courses of DHAP versus autologous stem-cell transplant (ASCT).

References

Velasquez WS, Cabanillas F, Salvador P, McLaughlin P, Fridrik M, Tucker S, Jagannath S, Hagemeister FB, Redman JR, Swan F, et al. Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP). Blood. 1988 Jan;71(1):117-22. link to original article contains verified protocol PubMed
Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, et al. 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 does not contain protocol PubMed

ESHAP

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

Regimen

Study	Evidence	Comparator	Efficacy
Velasquez et al. 1994	Phase III	ESHA	Superior RR
Avilés et al. 2010	Phase III	R-ESHAP	Seems not superior

Chemotherapy

Etoposide (Vepesid) 40 mg/m² IV over 1 hour once per day on days 1 to 4
Methylprednisolone (Solumedrol) 250-500 mg IV over 15 minutes once per day on days 1 to 5
Cytarabine (Cytosar) 2000 mg/m² IV over 2 hours once on day 5
Cisplatin (Platinol) 25 mg/m²/day IV continuous infusion on days 1 to 4 (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 "given regularly"

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

References

Velasquez WS, McLaughlin P, Tucker S, Hagemeister FB, Swan F, Rodriguez MA, Romaguera J, Rubenstein E, Cabanillas F. ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. J Clin Oncol. 1994 Jun;12(6):1169-76. 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

Gemcitabine (Gemzar)

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Regimen

Study	Evidence	Comparator
Fosså et al. 1999	Phase II
Pettengell et al. 2012	Phase III, <20 in this arm	Pixantrone

Chemotherapy

Gemcitabine (Gemzar) as follows:
- Cycle 1: 1250 mg/m² IV over 30 minutes once per day on days 1, 8, 15
- 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

4-week cycles until progression or intolerance

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
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 protocol PubMed

Ifosfamide (Ifex)

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Regimen

Study	Evidence	Comparator
Case et al. 1991 (CALGB 8552)	Phase II
Pettengell et al. 2012	Phase III, <20 in this arm	Pixantrone

Dose & schedule is as given in Pettengell et al. CALGB 8552 used a different dose & schedule.

Chemotherapy

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

Supportive medications

Mesna (Mesnex) dose not specified

28-day cycles

References

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. Review. link to original article PubMed
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

Oxaliplatin (Eloxatin)

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Regimen

Study	Evidence	Comparator
Germann et al. 1999	Phase II
Oki et al. 2005	Phase II
Pettengell et al. 2012	Phase III, <20 in this arm	Pixantrone

Germann et al. give a range of 100 to 130 mg/m²; Oki et al. used the 130 mg/m² dosage; Pettengell et al. used the 100 mg/m² dosage.

Chemotherapy

Oxaliplatin (Eloxatin) 100 to 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. Review. 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
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

Panobinostat (Farydak)

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Regimen

Study	Evidence	ORR	Comparator	Comparator ORR	Pt Population
Assouline et al. 2016	Randomized Phase II	29% (95% CI 11-52%)	Panobinostat & Rituximab	26% (95% CI 9-51%)	Median of 2 prior treatments (range 1-8)

Chemotherapy

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

21-day cycles until progression or intolerance

References

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 PubMed

Panobinostat & Rituximab

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Regimen

Study	Evidence	ORR	Comparator	Comparator ORR	Pt Population
Assouline et al. 2016	Randomized Phase II, <20 pts	26% (95% CI 9-51%)	Panobinostat	29% (95% CI 11-52%)	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 until progression or intolerance

References

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 PubMed

Pixantrone (Pixuvri)

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Regimen

Study	Evidence	Comparator	Efficacy
Pettengell et al. 2012	Phase III	Etoposide Gemcitabine Ifosfamide Mitoxantrone Oxaliplatin Vinorelbine	Seems to have superior RR

Chemotherapy

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

28-day cycle for up to 6 cycles

References

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 PubMed

R-DHAP

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

Regimen #1

Study	Evidence	Comparator	Efficacy
Crump et al. 2014 (NCIC-CTG LY.12)	Phase III	R-GDP	Seems non-inferior

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 (Cytosar) 2000 mg/m² IV over 3 hours Q12H x 2 doses on day 2 (total of 2 doses)
Cisplatin (Platinol) 100 mg/m² IV continuous infusion over 24 hours on day 1

21-day cycle for up to 3 cycles

Responders proceeded to stem-cell mobilization and autologous hematopoietic cell transplant.

Regimen #2

Study	Evidence	Comparator	Efficacy
Gisselbrecht et al. 2010 (CORAL)	Phase III	R-ICE	Seems not superior

Note: the paper 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 before other chemotherapy):
- Cycle 1: 375 mg/m² IV once per day on days -1 & 1
- Cycle 2: 375 mg/m² IV once on day 1
Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
Cytarabine (Cytosar) 2000 mg/m² IV over 3 hours Q12H x 2 doses on day 2 (total of 2 doses)
Cisplatin (Platinol) 100 mg/m² IV continuous infusion over 24 hours on day 1

Supportive medications

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

Patients with complete or partial response then received BEAM -> autologous stem-cell transplant.

References

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. link to original article 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 PubMed
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-ESHAP

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

Regimen

Study	Evidence	Comparator	Efficacy
Martín et al. 2008	Retrospective
Avilés et al. 2010	Phase III	ESHAP	Seems not superior

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 1 hour 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, methylprednisolone 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 (Cytosar) 2000 mg/m² IV over 2 hours once on day 5
Cisplatin (Platinol) 25 mg/m²/day IV continuous infusion over 96 hours (total dose per cycle: 100 mg/m²) on days 1 to 4

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 "given regularly"

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

References

Velasquez WS, McLaughlin P, Tucker S, Hagemeister FB, Swan F, Rodriguez MA, Romaguera J, Rubenstein E, Cabanillas F. ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. J Clin Oncol. 1994 Jun;12(6):1169-76. link to original article contains verified protocol 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. 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

Study	Evidence	Comparator	Efficacy
Crump et al. 2014 (NCIC-CTG LY.12)	Phase III	R-DHAP	Seems non-inferior

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

Responders proceeded to stem-cell mobilization and autologous hematopoietic cell transplant.

References

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

Regimen

Study	Evidence	Comparator	Efficacy
Gisselbrecht et al. 2010 (CORAL)	Phase III	R-DHAP	Seems not superior

Note: the paper refers to the non-randomized Kewalramani et al. 2004 regimen, 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) 5,000 mg/m² IV continuous infusion over 24 hours on day 2
Carboplatin (Paraplatin) AUC 5 IV (maximum dose of 800 mg per cycle) 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 in the paper
" Granulocyte colony-stimulating factor was administered after R-ICE"

21-day cycle for 3 cycles

Patients with complete or partial response then received BEAM autologous stem-cell transplant.

References

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 PubMed
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

Vinorelbine (Navelbine)

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Regimen

Study	Evidence	Comparator
Balzarotti et al. 1996	Non-randomized, <20 patients in this subgroup
Pettengell et al. 2012	Phase III, <20 in this arm	Pixantrone

Chemotherapy

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

28-day 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. Review. link to original article PubMed
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

Relapsed/refractory, non-randomized or retrospective data

Blinatumomab (Blincyto)

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Regimen

Study	Evidence
Viardot et al. 2016	Phase II

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

Chemotherapy

Blinatumomab (Blincyto) as follows:
- 9 µg/day IV continuous infusion during week 1, then
- 28 µg/day IV continuous infusion during week 2, then
- 112 µg/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 TID for 2 days following infusion start and dose increases
- Patients with neurologic symptoms or cytokine release syndrome received 8 mg PO/IV Q8H 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

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 PubMed

BR

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BR: Bendamustine, Rituximab

Regimen

Study	Evidence
Ohmachi et al. 2013	Phase II
Vacirca et al. 2013	Phase II

Note: Bendamustine was given on days 2 & 3 by Ohmachi et al. and on days 1 & 2 by Vacirca et al.

Chemotherapy

Note: the bendamustine infusion instructions are for the Treanda formulation, which was discontinued on 3/31/2016.

Bendamustine 120 mg/m² IV over 60 minutes once per day on days 1 & 2 OR on days 2 & 3
Rituximab (Rituxan) 375 mg/m² IV once on day 1

Supportive medications

"Opportunistic infection prophylaxis with Trimethoprim/Sulfamethoxazole (Bactrim DS) and Acyclovir (Zovirax) was recommended."

21-day cycle for up to 6 cycles

References

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
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 PubMed

Brentuximab vedotin (Adcetris)

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Regimen

Study	Evidence
Bartlett et al. 2014	Phase II
Jacobsen et al. 2015	Phase II

Bartlett et al. treated patients with undetectable CD30 by visual assessment using routine IHC. Jacobsen et al. treated patients with CD30+ non-Hodgkin lymphoma, as determined by IHC.

Chemotherapy

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

21-day cycles, given until progression or unacceptable toxicity

References

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 link to abstract
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

EPOCH

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EPOCH: Etoposide, Prednisone, Oncovin, Cyclophosphamide, Hydroxydaunorubicin

Synonyms: CHEOP

Structured Concept: C63779 (NCI-T), C1880475 (NCI-MT/UMLS)

Regimen

Study	Evidence
Wilson et al. 1993	Phase II

Chemotherapy

Etoposide (Vepesid) 50 mg/m²/day (total dose per cycle: 200 mg/m²) IV continuous infusion on days 1 to 4
Prednisone (Sterapred) 60 mg/m² PO on days 1 to 6
Vincristine (Oncovin) 0.4 mg/m²/day (total dose per cycle: 1.6 mg/m²) IV continuous infusion on days 1 to 4
Cyclophosphamide (Cytoxan) 750 mg/m² IV over 15 minutes on day 6
Doxorubicin (Adriamycin) 10 mg/m²/day (total dose per cycle: 40 mg/m²) IV continuous infusion on days 1 to 4

Supportive medications

Filgrastim (Neupogen) 5 mcg/kg SQ once per day, starting on day 6 and continuing until ANC >5,000/uL past nadir
PCP prophylaxis with any one of the following:
- Trimethoprim/Sulfamethoxazole (Bactrim DS) 160/800 mg PO BID 3 days per week
- Atovaquone (Mepron) 1500 mg PO once per day
- Pentamidine (Nebupent) 300 mg nebulized every 28 days

21-day cycle for 6 to 8 cycles

References

Wilson WH, Bryant G, Bates S, Fojo A, Wittes RE, Steinberg SM, Kohler DR, Jaffe ES, Herdt J, Cheson BD et al. EPOCH chemotherapy: toxicity and efficacy in relapsed and refractory non-Hodgkin's lymphoma. J Clin Oncol. 1993 Aug;11(8):1573-82 link to original article contains verified protocol PubMed

Everolimus (Afinitor)

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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, given until progression or unacceptable toxicity

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 PubMed

Everolimus & Rituximab

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Regimen

Study	Evidence
Barnes et al. 2013	Phase II

Chemotherapy

Everolimus (Afinitor) 5 mg PO once per day on days 1 to 14, increased to 10 mg PO once per day for the remainder of cycle 1 and thereafter, if tolerated
Rituximab (Rituxan) 375 mg/m² IV once per week x 4 weeks, then once on day 1 of cycle 2 onwards

28-day cycle for 6 cycles Responders had the option of continuing everolimus for another 6 months.

References

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 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
Doxorubicin liposomal (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 (Zevalin)

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Regimen

To be completed

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 (Imbruvica)

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Regimen

Study	Evidence
Wilson et al. 2012	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

Duration not specified

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). link to abstract

ICE

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ICE: Ifosfamide, Carboplatin, Etoposide

Regimen

Study	Evidence
Zelenetz et al. 2003	Phase II

Third cycle intended to be followed by peripheral blood hematopoietic cell collection

Chemotherapy

Ifosfamide (Ifex) 5,000 mg/m² IV continuous infusion over 24 hours on day 2, mixed together with Mesna (Mesnex)
Carboplatin (Paraplatin) AUC 5 (maximum dose of 800 mg per cycle) IV bolus once on day 2
- Carboplatin AUC calculated based on a 12-hour creatinine clearance
Etoposide (Vepesid) 100 mg/m² IV bolus once per day on days 1 to 3

14-day cycle for 3 cycles

Supportive medications

Mesna (Mesnex) 5,000 mg/m² IV continuous infusion over 24 hours on day 2, mixed together with Ifosfamide (Ifex)
Filgrastim (Neupogen) 5 µg/kg SC once per day on days 5 to 12 (10 µg/kg with cycle 3, given until collection of peripheral blood hematopoietic cells)

References

Moskowitz CH, Bertino JR, Glassman JR, Hedrick EE, Hunte S, Coady-Lyons N, Agus DB, Goy A, Jurcic J, Noy A, O'Brien J, Portlock CS, Straus DS, Childs B, Frank R, Yahalom J, Filippa D, Louie D, Nimer SD, Zelenetz AD. Ifosfamide, carboplatin, and etoposide: a highly effective cytoreduction and peripheral-blood progenitor-cell mobilization regimen for transplant-eligible patients with non-Hodgkin's lymphoma. J Clin Oncol. 1999 Dec;17(12):3776-85. link to original article 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. link to original article contains verified protocol PubMed
Hertzberg MS, Crombie C, Benson W, Taper J, Gottlieb D, Bradstock KF. Outpatient-based ifosfamide, carboplatin and etoposide (ICE) chemotherapy in transplant-eligible patients with non-Hodgkin's lymphoma and Hodgkin's disease. Ann Oncol. 2003;14 Suppl 1:i11-6. link to original article PubMed

Lenalidomide (Revlimid)

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Regimen

Study	Evidence
Wiernik et al. 2008 (NHL-002)	Phase II
Witzig et al. 2011 (NHL-003)	Phase II

Chemotherapy

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

28-day cycles until disease progression or unacceptable toxicity

References

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
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

Lenalidomide & Rituximab

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Regimen #1

Study	Evidence
Wang et al. 2013	Phase II

Chemotherapy

Lenalidomide (Revlimid) 20 mg PO once per day on days 1 to 21
Rituximab (Rituxan) 375 mg/m² IV once per week on weeks 1 to 4 of cycle 1, only

28-day cycles

Regimen #2

Study	Evidence
Zinzani et al. 2011	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

Patients with a response of stable disease or better proceeded to maintenance lenalidomide.

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
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 (Novantrone)

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Regimen

Study	Evidence
Bajetta et al. 1988	Phase II

Chemotherapy

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

3-week 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
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 (Gazyva)

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Regimen

Study	Evidence
Morschhauser et al. 2013 (GAUGUIN)	Phase II

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 30 minutes prior to Obinutuzumab (Gazyva)
"An antihistamine" 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

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

O-DHAP

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

Regimen

Study	Evidence
Matasar et al. 2013	Phase II

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 PO/IV once per day on days 1 to 4
Cytarabine (Cytosar) 2000 mg/m² IV Q12H x 2 doses on day 2 (total of 2 doses)
Cisplatin (Platinol) 100 mg/m² IV continuous infusion over 24 hours on day 1

Supportive medications

G-CSF or Neulasta was recommended (no details given).

21-day cycle for 3 cycles

References

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 PubMed

O-ICE

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O-ICE: Ofatumumab, Ifosfamide, Carboplatin, Etoposide

Regimen

Study	Evidence
Matasar et al. 2013	Phase II

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) 5,000 mg/m² IV continuous infusion over 24 hours on day 2, mixed together with Mesna (Mesnex)
Carboplatin (Paraplatin) AUC 5 (maximum dose of 800 mg) IV once on day 1 OR 2 (1 dose, total)
- 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 on day 2, mixed together with Ifosfamide (Ifex)
G-CSF or Neulasta was recommended (no details given).

21-day cycle for 3 cycles

References

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 PubMed

Ofatumumab (Arzerra)

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Regimen

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

Chemotherapy

Ofatumumab (Arzerra) 300 mg IV on cycle 1 day 1, then 1000 mg IV once per week x 7 weeks (total of 8 doses)

Supportive medications

Acetaminophen (Tylenol) 1000 mg or equivalent 30 min to 2 h prior to Ofatumumab (Arzerra)
Cetirizine (Zyrtec) 10 mg PO or equivalent 30 min to 2 h prior to Ofatumumab (Arzerra)
Prednisolone (Millipred) 100 mg (route not specified) or equivalent 30 min to 2 h prior to Ofatumumab (Arzerra) for first 2 infusions, only

One course

References

Coiffier B, Radford J, Bosly A, Martinelli 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

R-BL

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R-BL: Rituximab, Bendamustine, Lenalidomide

Regimen

Study	Evidence	ORR
Hitz et al. 2016 (SAKK 38/08)	Phase II	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	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

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-DexaBEAM

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

Regimen

Study	Evidence
Kirschey et al. 2014	Phase II

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Dexamethasone (Decadron) 24 mg PO TID on days 1 to 10
Carmustine (BiCNU) 60 mg/m² IV once on day 2
Etoposide (Vepesid) 75 mg/m² IV once per day on days 4 to 7
Cytarabine (Cytosar) 200 mg/m² IV BID on days 4 to 7
Melphalan (Alkeran) 20 mg/m² IV once on day 3

3- to 4-week cycle for 2 cycles

Patient proceed to undergo high dose therapy and autologous hematopoietic cell transplant.

References

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-DHAP

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

Regimen

Study	Evidence
Mey et al. 2006	Phase II

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

First cycle

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Dexamethasone (Decadron) 40 mg PO once per day on days 3 to 5
Cytarabine (Cytosar) as follows:
- Younger than 60 years: 1000 mg/m² IV over 2 hours Q12H x 2 doses on day 4 (total of 2 doses)
- Older than 60 years: 500 mg/m² IV over 2 hours Q12H x 2 doses on day 4 (total of 2 doses)
Cisplatin (Platinol) 25 mg/m²/day IV continuous infusion on days 3 to 5 (total dose: 75 mg/m²)

3-week cycle

Subsequent cycles

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Dexamethasone (Decadron) 40 mg PO once per day on days 3 to 6
Cytarabine (Cytosar) as follows:
- Younger than 60 years: 2000 mg/m² IV over 2 hours Q12H x 2 doses on day 4 (total of 2 doses)
- Older than 60 years: 1000 mg/m² IV over 2 hours Q12H x 2 doses on day 4 (total of 2 doses)
Cisplatin (Platinol) 25 mg/m²/day IV continuous infusion on days 3 to 6 (total dose per cycle: 100 mg/m²)

3-week cycle up to 3 cycles (4 cycles, total)

Patients with complete or partial response were allowed to undergo autologous stem-cell transplant.

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

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 on day 1
Etoposide (Vepesid) 65 mg/m²/day (total dose per cycle: 195 mg/m²) IV continuous infusion on days 2 to 4
Prednisone (Sterapred) 60 mg/m²/day PO on days 1 to 14
Vincristine (Oncovin) 0.5 mg/m²/day (total dose per cycle: 1.5 mg/m²) IV continuous infusion on days 2 to 4
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 5
Doxorubicin (Adriamycin) 15 mg/m²/day (total dose per cycle: 45 mg/m²) IV continuous infusion on days 2 to 4

21-day cycle for 4 to 6 cycles

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-GDP

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

Regimen

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

R-GemOx

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R-GemOx: Rituximab, Gemcitabine, Oxaliplatin

Regimen #1 "GEMOX-R"

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

Regimen #2

Study	Evidence
El Gnaoui et al. 2007	Phase II

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Gemcitabine (Gemzar) 1000 mg/m² IV at a fixed dose rate of 10 mg/m²/min 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 prior to Rituximab (Rituxan)
Acetaminophen (Tylenol) 1000 mg PO once prior to Rituximab (Rituxan)
Dexchlorpheniramine (Polaramine) 6 mg PO once prior to Rituximab (Rituxan)
Primary prophylaxis with G-CSF was not permitted

14-day cycle for up 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 PubMed

R-ICE

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R-ICE: Rituximab, Ifosfamide, Carboplatin, Etoposide

Regimen #1

Study	Evidence
Guo et al. 2014	Phase II

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Ifosfamide (Ifex) 1,600 mg/m² IV once per day on days 2 to 4
Carboplatin (Paraplatin) AUC 5 (maximum dose of 800 mg per cycle) 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 #2

Study	Evidence
Zelenetz et al. 2003	Phase II
Kewalramani et al. 2004	Phase II

Third cycle intended to be followed by peripheral blood hematopoietic cell collection

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
- An additional one-time dose of Rituximab (Rituxan) 375 mg/m² IV was given 48 hours before the beginning of cycle 1
Ifosfamide (Ifex) 5,000 mg/m² IV continuous infusion over 24 hours on day 4, mixed together with Mesna (Mesnex)
Carboplatin (Paraplatin) AUC 5 (maximum dose of 800 mg per cycle) 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

14-day cycle for 3 cycles

Supportive medications

(as described by Kewalramani et al. 2004):
Mesna (Mesnex) 5,000 mg/m² IV continuous infusion over 24 hours on day 4, mixed together 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 µg/kg SC once per day on days 7 to 14 (10 µg/kg with cycle 3, given until collection of peripheral blood hematopoietic cells)

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 regimen 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 PubMed

RICER

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

Regimen

Study	Evidence
Feldman et al. 2014	Phase II

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Ifosfamide (Ifex) 5,000 mg/m² IV continuous infusion over 24 hours on day 2, mixed together with Mesna (Mesnex)
Carboplatin (Paraplatin) AUC 5 (maximum dose of 800 mg per cycle) 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) 5,000 mg/m² IV continuous infusion over 24 hours on day 2, mixed together with Ifosfamide (Ifex)
Aspirin 81 mg PO once per day from day 1 until platelets < 50,000
Low dose LMWH for patients intolerant of Aspirin
" Granulocyte colony-stimulating factor was administered after R-ICE"

14-day cycle for 2 cycles

Responders received a 3rd cycle with hematopoietic cell collection 10 to 14 days afterwards, followed by autologous hematopoietic cell transplant.

References

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 PubMed

R-IFE

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R-IFE: Rituximab, IFosfamide, Etoposide

Regimen

Study	Evidence
Pardal et al. 2014	Phase II

Treatment preceded by R-MegaCHOP x3; these were patients with PET-positive disease at interim assessment.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Ifosfamide (Ifex) 10,000 mg/m² IV continuous infusion over 72 hours on days 1 to 3
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)

Responders proceeded to undergo autologous hematopoietic cell transplant.

References

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
Gyan et al. 2013	Phase II

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 IV continuous infusion from day 1 to 5 (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
Pegfilgrastim (Neulasta) 6 mg SC once on day 7 was recommended
Epoietin alpha support was recommended for Hgb < 10 g/dL

28-day cycle for 3 cycles

Responders were recommended to undergo 3 additional cycles or autologous hematopoietic cell transplant.

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

Temsirolimus (Torisel)

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Regimen

Study	Evidence
Smith et al. 2010	Phase II

Chemotherapy

Temsirolimus (Torisel) 25 mg IV over 30 minutes once per week

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 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 µg/kg SC once per day from day 7 until neutrophil recovery
Dexamethasone (Decadron) 20 mg IV once 30 minutes prior to Paclitaxel (Taxol)
Diphenhydramine (Benadryl) 50 mg IV once 30 minutes prior to Paclitaxel (Taxol)

21-day cycle up to a maximum of 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 PubMed

Consolidation and/or maintenance after salvage therapy

Autologous hematopoietic cell transplant

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Regimen #1

Study	Evidence	Comparator	Efficacy
Philip et al. 1995 (PARMA)	Phase III	DHAP x4	Seems to have superior OS

Treatment preceded by DHAP x 2. Radiation was also given to sites of bulky disease (>5cm); see paper for details.

BEAC followed by autologous hematopoietic cell transplant

Follow the link for details.

Regimen #2

Study	Evidence
Gisselbrecht et al. 2010 (CORAL)	Non-randomized
Pardal et al. 2014	Phase II

Treatment in CORAL preceded by R-ICE x 3 versus R-DHAP x 3. Treatment in Pardal et al. 2014 preceded by R-MegaCHOP x3 and R-IFE x 2.

BEAM followed by autologous hematopoietic cell transplant

Follow the link for details. In CORAL, treatment was followed by maintenance rituximab versus observation.

Regimen #3

Study	Evidence
Feldman et al. 2014	Phase II

Treatment preceded by RICER x 3.

BEAM followed by autologous hematopoietic cell transplant

Follow the link for details. If patients were fully recovered within 90 days, they proceeded to lenalidomide maintenance.

Regimen #4

Study	Evidence
Kirschey et al. 2014	Phase II

Treatment preceded by R-DexaBEAM x 2.

R-BEAM or R-TBI/Cy followed by autologous hematopoietic cell transplant

References

Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, et al. 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
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 PubMed
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 PubMed
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
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
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

Lenalidomide (Revlimid)

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Regimen #1

Study	Evidence
Feldman et al. 2014	Phase II

Treatment preceded by BEAM autologous transplant.

Chemotherapy

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

28-day cycles for up to 12 months

Regimen #2

Study	Evidence
Zinzani et al. 2011	Phase II

Treatment preceded by lenalidomide & rituximab x 4.

Chemotherapy

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

28-day cycle for 8 months

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
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 PubMed

Observation

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Regimen

Study	Evidence	Comparator	Efficacy
Gisselbrecht et al. 2012 (CORAL)	Phase III	Rituximab	Seems not superior

No further treatment after BEAM autologous hematopoietic cell transplant.

References

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 PubMed

Rituximab (Rituxan)

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Regimen

Study	Evidence	Comparator	Efficacy
Gisselbrecht et al. 2012 (CORAL)	Phase III	Observation	Seems not superior

Treatment preceded by BEAM autologous hematopoietic cell transplant, and begins on day +28.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once every 8 weeks

1 year course

References

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 PubMed

Response criteria

NCI Sponsored International Working Group Criteria (1999)

Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-López A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999 Apr;17(4):1244. Review. Erratum in: J Clin Oncol 2000 Jun;18(11):2351. link to original article PubMed

Revised International Prognostic Index, R-IPI (2007)

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

International Harmonization Project on Lymphoma revised criteria (2007)

Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V; International Harmonization Project on Lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007 Feb 10;25(5):579-86. Epub 2007 Jan 22. link to original article PubMed

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

CNS-IPI (2016)

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Risk factors

Age > 60 years
Elevated LDH
ECOG PS > 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 < 5%)
Intermediate risk: 2 or 3 risk factors (2-year rate of CNS disease < 5%)
High risk: 4 to 6 risk factors (2-year rate of CNS disease > 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 23: / Line 23: @@
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|-
+|[http://bloodjournal.hematologylibrary.org/content/104/3/626.long Pfreundschuh et al. 2004 (NHL-B1)]
+|style="background-color:#eeee00"|Non-randomized portion of RCT
 |-
 |[http://bloodjournal.hematologylibrary.org/content/104/3/634.long Pfreundschuh et al. 2004 (NHL-B2)]
-|<span
+|style="background-color:#eeee00"|Non-randomized
-style="background:#eeee00;
+|-
-padding:3px 6px 3px 6px;
+|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2808%2970002-0/fulltext Pfreundschuh et al. 2008 (RICOVER-60)]
-border-color:black;
+|style="background-color:#eeee00"|Non-randomized portion of RCT
-border-width:2px;
+|-
-border-style:solid;">Non-randomized</span>
+|[http://jco.ascopubs.org/content/32/36/4127.full Pfreundschuh et al. 2014 (SMARTE-R-CHOP-14)]
+|style="background-color:#eeee00"|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.''
-''Recommended "to improve the performance status of patients and to ameliorate side-effects of the first chemotherapy cycle."''
 ====Chemotherapy====
 *[[Vincristine (Oncovin)]] 1 mg IV once (day not specified)
@@ Line 41: / Line 44: @@
 '''7-day course'''
-''Treatment followed immediately by [[#CHOP|CHOP]].''
+''Treatment in '''NHL-B1''' and '''NHL-B2''' followed by randomization to [[#CHOP|CHOP]] versus [[#CHOP_Intensified|CHOP-14]] versus [[Diffuse_large_B-cell_lymphoma_-_obsolete#CHOEP|CHOEP]] versus CHOEP-14. Treatment in '''RICOVER-60''' followed by randomization to [[#CHOP_Intensified|CHOP-14]] versus [[#R-CHOP_Intensified|R-CHOP-14]]. Treatment in '''SMARTE-R-CHOP-14''' followed by [[#R-CHOP_Intensified|R-CHOP-14]].''
 ===References===
-# 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://bloodjournal.hematologylibrary.org/content/104/3/634.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15016643 PubMed]
+# 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://bloodjournal.hematologylibrary.org/content/104/3/626.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14982884 PubMed]
+# 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://bloodjournal.hematologylibrary.org/content/104/3/634.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15016643 PubMed]
+# 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. [http://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]
+# 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]
 =Untreated, randomized data=
@@ Line 68: / Line 74: @@
 |-
 |[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61040-4/fulltext Récher et al. 2011 (LNH03-2B)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Diffuse_large_B-cell_lymphoma#R-CHOP|R-CHOP]]
-|<span title=="3-year OS 92% (ACVBP-R) vs. 84% (R-CHOP)"
+|style="background-color:#00cd00"|Superior OS
-style="background:#00CD00;
+|style="background-color:#ff0000"|Increased toxicity
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Improved OS</span>
-|<span
-style="background:#ff0000;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Increased toxicity</span>
 |-
 |[http://annonc.oxfordjournals.org/content/24/4/1032.long Ketterer et al. 2013 (LNH03-1B)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Diffuse_large_B-cell_lymphoma_-_obsolete#ACVBP|ACVBP]]
-|
+|style="background-color:#00cd00"|Seems to have superior PFS
-|
+|style="background-color:#eeee00"|Similar toxicity
 |-
 |}
@@ Line 119: / Line 105: @@
 ===References===
-# 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. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61040-4/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22118442 PubMed]
+# 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. [http://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]
-# 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] [http://www.ncbi.nlm.nih.gov/pubmed/23235801 PubMed]
+# 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]
 ==CHOP {{#subobject:4ca454|Regimen=1}}==
@@ Line 179: / Line 165: @@
 |-
 |}
-''Treatment in '''NHL-B2''' preceded by [[#Vincristine_.26_Prednisone|pre-phase vincristine & prednisone]].''
+''Treatment in '''NHL-B1''' and '''NHL-B2''' preceded by [[#Vincristine_.26_Prednisone|pre-phase vincristine & prednisone]].''
 ====Chemotherapy====
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 186: / Line 172: @@
 *[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
-Supportive medications (per '''NHL-B1''' and '''NHL-B2'''):
+====Supportive medications====
-*At the discretion of ordering physician: [[Filgrastim (Neupogen)]] 300 mcg (for patients <75 kg) or 480 mcg (for patients at least 75 kg) SC once per day on days 4 to 13
+*Per '''NHL-B1''' and '''NHL-B2''': At the discretion of ordering physician: [[Filgrastim (Neupogen)]] 300 mcg (for patients <75 kg) or 480 mcg (for patients at least 75 kg) SC once per day on days 4 to 13
 '''21-day cycle for 6 cycles'''
@@ Line 274: / Line 260: @@
 ===References===
-# McKelvey EM, Gottlieb JA, Wilson HE, Haut A, Talley RW, Stephens R, Lane M, Gamble JF, Jones SE, Grozea PN, Gutterman J, Coltman C, Moon TE. Hydroxyldaunomycin (Adriamycin) combination chemotherapy in malignant lymphoma. Cancer. 1976 Oct;38(4):1484-93. [http://www.ncbi.nlm.nih.gov/pubmed/791473 PubMed]
+# McKelvey EM, Gottlieb JA, Wilson HE, Haut A, Talley RW, Stephens R, Lane M, Gamble JF, Jones SE, Grozea PN, Gutterman J, Coltman C, Moon TE. Hydroxyldaunomycin (Adriamycin) combination chemotherapy in malignant lymphoma. Cancer. 1976 Oct;38(4):1484-93. [https://www.ncbi.nlm.nih.gov/pubmed/791473 PubMed]
-# Elias L, Portlock CS, Rosenberg SA. Combination chemotherapy of diffuse histiocytic lymphoma with cyclophosphamide, adriamycin, vincristine and prednisone (CHOP). Cancer. 1978 Oct;42(4):1705-10. [http://onlinelibrary.wiley.com/doi/10.1002/1097-0142(197810)42:4%3C1705::AID-CNCR2820420408%3E3.0.CO;2-P/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/361209 PubMed]
+# Elias L, Portlock CS, Rosenberg SA. Combination chemotherapy of diffuse histiocytic lymphoma with cyclophosphamide, adriamycin, vincristine and prednisone (CHOP). Cancer. 1978 Oct;42(4):1705-10. [http://onlinelibrary.wiley.com/doi/10.1002/1097-0142(197810)42:4%3C1705::AID-CNCR2820420408%3E3.0.CO;2-P/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/361209 PubMed]
-# Pavlovsky S, Santarelli MT, Erazo A, Diaz Maqueo JC, Somoza N, Lluesma Goñalons M, Cervantes G, Garcia Vela EL, Corrado C, Magnasco H, et al. Results of a randomized study of previously-untreated intermediate and high grade lymphoma using CHOP versus CNOP. Ann Oncol. 1992 Mar;3(3):205-9. [http://annonc.oxfordjournals.org/content/3/3/205.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/1586618 PubMed]
+# Pavlovsky S, Santarelli MT, Erazo A, Diaz Maqueo JC, Somoza N, Lluesma Goñalons M, Cervantes G, Garcia Vela EL, Corrado C, Magnasco H, et al. Results of a randomized study of previously-untreated intermediate and high grade lymphoma using CHOP versus CNOP. Ann Oncol. 1992 Mar;3(3):205-9. [http://annonc.oxfordjournals.org/content/3/3/205.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/1586618 PubMed]
-# Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med. 1993 Apr 8;328(14):1002-6. [http://www.nejm.org/doi/full/10.1056/NEJM199304083281404 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/7680764 PubMed]
+# Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med. 1993 Apr 8;328(14):1002-6. [http://www.nejm.org/doi/full/10.1056/NEJM199304083281404 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7680764 PubMed]
-## '''Update:''' Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP. A phase III comparison of CHOP vs. m-BACOD vs. ProMACE-CytaBOM vs. MACOP-B in patients with intermediate- or high-grade non-Hodgkin's lymphoma: results of SWOG-8516 (Intergroup 0067), the National High-Priority Lymphoma Study. Ann Oncol. 1994;5 Suppl 2:91-5. [http://www.ncbi.nlm.nih.gov/pubmed/7515652 PubMed]
+## '''Update:''' Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP. A phase III comparison of CHOP vs. m-BACOD vs. ProMACE-CytaBOM vs. MACOP-B in patients with intermediate- or high-grade non-Hodgkin's lymphoma: results of SWOG-8516 (Intergroup 0067), the National High-Priority Lymphoma Study. Ann Oncol. 1994;5 Suppl 2:91-5. [https://www.ncbi.nlm.nih.gov/pubmed/7515652 PubMed]
-## '''Update:''' Bernstein SH, Unger JM, Leblanc M, Friedberg J, Miller TP, Fisher RI. Natural history of CNS relapse in patients with aggressive non-Hodgkin's lymphoma: a 20-year follow-up analysis of SWOG 8516 -- the Southwest Oncology Group. J Clin Oncol. 2009 Jan 1;27(1):114-9. Epub 2008 Dec 1. [http://jco.ascopubs.org/content/27/1/114.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/19047289 PubMed]
+## '''Update:''' Bernstein SH, Unger JM, Leblanc M, Friedberg J, Miller TP, Fisher RI. Natural history of CNS relapse in patients with aggressive non-Hodgkin's lymphoma: a 20-year follow-up analysis of SWOG 8516 -- the Southwest Oncology Group. J Clin Oncol. 2009 Jan 1;27(1):114-9. Epub 2008 Dec 1. [http://jco.ascopubs.org/content/27/1/114.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19047289 PubMed]
-# Tondini C, Zanini M, Lombardi F, Bengala C, Rocca A, Giardini R, Buzzoni R, Valagussa P, Bonadonna G. Combined modality treatment with primary CHOP chemotherapy followed by locoregional irradiation in stage I or II histologically aggressive non-Hodgkin's lymphomas. J Clin Oncol. 1993 Apr;11(4):720-5. [http://jco.ascopubs.org/content/11/4/720.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/8478665 PubMed]
+# Tondini C, Zanini M, Lombardi F, Bengala C, Rocca A, Giardini R, Buzzoni R, Valagussa P, Bonadonna G. Combined modality treatment with primary CHOP chemotherapy followed by locoregional irradiation in stage I or II histologically aggressive non-Hodgkin's lymphomas. J Clin Oncol. 1993 Apr;11(4):720-5. [http://jco.ascopubs.org/content/11/4/720.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8478665 PubMed]
-# 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. [http://www.nejm.org/doi/full/10.1056/NEJM199807023390104 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/9647875 PubMed]
+# 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. [http://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] [http://www.ncbi.nlm.nih.gov/pubmed/27382104 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/pubmed/27382104 PubMed]
-# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa011795 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11807147 PubMed]
+# 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. [http://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:''' 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''' [http://www.ncbi.nlm.nih.gov/pubmed/15867204 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]
-## '''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://bloodjournal.hematologylibrary.org/content/116/12/2040.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20548096 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://bloodjournal.hematologylibrary.org/content/116/12/2040.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20548096 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] [http://www.ncbi.nlm.nih.gov/pubmed/22301063 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]
-# Tilly H, Lepage E, Coiffier B, Blanc M, Herbrecht R, Bosly A, Attal M, Fillet G, Guettier C, Molina TJ, Gisselbrecht C, Reyes F; Groupe d'Etude des Lymphomes de l'Adulte. Intensive conventional chemotherapy (ACVBP regimen) compared with standard CHOP for poor-prognosis aggressive non-Hodgkin lymphoma. Blood. 2003 Dec 15;102(13):4284-9. Epub 2003 Aug 14. [http://www.bloodjournal.org/content/102/13/4284.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12920037 PubMed]
+# Tilly H, Lepage E, Coiffier B, Blanc M, Herbrecht R, Bosly A, Attal M, Fillet G, Guettier C, Molina TJ, Gisselbrecht C, Reyes F; Groupe d'Etude des Lymphomes de l'Adulte. Intensive conventional chemotherapy (ACVBP regimen) compared with standard CHOP for poor-prognosis aggressive non-Hodgkin lymphoma. Blood. 2003 Dec 15;102(13):4284-9. Epub 2003 Aug 14. [http://www.bloodjournal.org/content/102/13/4284.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12920037 PubMed]
-# 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://bloodjournal.hematologylibrary.org/content/104/3/626.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/14982884 PubMed]
+# 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://bloodjournal.hematologylibrary.org/content/104/3/626.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14982884 PubMed]
-# 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://bloodjournal.hematologylibrary.org/content/104/3/634.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15016643 PubMed]
+# 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://bloodjournal.hematologylibrary.org/content/104/3/634.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15016643 PubMed]
-# 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] [http://www.ncbi.nlm.nih.gov/pubmed/15210738 PubMed]
+# 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]
-# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa042040 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/15788496 PubMed]
+# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa042040 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15788496 PubMed]
-# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2806%2970664-7/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16648042 PubMed]
+# 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. [http://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:''' 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2811%2970235-2/fulltext link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22118442 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. [http://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/22118442 PubMed]
-# 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''' [http://www.ncbi.nlm.nih.gov/pubmed/16754935 PubMed]
+# 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]
-# 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. [http://jco.ascopubs.org/content/25/7/787.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17228021 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. [http://jco.ascopubs.org/content/25/7/787.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17228021 PubMed]
 <!-- Presented orally and in abstract form at the 47th annual meeting of the American Society of Hematology, Atlanta, Georgia, December 11, 2005. -->
-# Verdonck LF, Notenboom A, de Jong DD, MacKenzie MA, Verhoef GE, Kramer MH, Ossenkoppele GJ, Doorduijn JK, Sonneveld P, van Imhoff GW. Intensified 12-week CHOP (I-CHOP) plus G-CSF compared with standard 24-week CHOP (CHOP-21) for patients with intermediate-risk aggressive non-Hodgkin lymphoma: a phase 3 trial of the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON). Blood. 2007 Apr 1;109(7):2759-66. [http://bloodjournal.hematologylibrary.org/content/109/7/2759.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17132720 PubMed]
+# Verdonck LF, Notenboom A, de Jong DD, MacKenzie MA, Verhoef GE, Kramer MH, Ossenkoppele GJ, Doorduijn JK, Sonneveld P, van Imhoff GW. Intensified 12-week CHOP (I-CHOP) plus G-CSF compared with standard 24-week CHOP (CHOP-21) for patients with intermediate-risk aggressive non-Hodgkin lymphoma: a phase 3 trial of the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON). Blood. 2007 Apr 1;109(7):2759-66. [http://bloodjournal.hematologylibrary.org/content/109/7/2759.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17132720 PubMed]
 ==CHOP Intensified {{#subobject:6f7a21|Regimen=1}}==
@@ Line 317: / Line 303: @@
 |-
 |[http://jco.ascopubs.org/content/21/13/2466.long Blayney et al. 2003 (CHOP-DI, SWOG 9349)]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 343: / Line 324: @@
 |-
 |[http://bloodjournal.hematologylibrary.org/content/109/7/2759.long Verdonck et al. 2007]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00cd00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Diffuse_large_B-cell_lymphoma#CHOP|CHOP]]
 |-
@@ Line 370: / Line 346: @@
 |-
 |[http://bloodjournal.hematologylibrary.org/content/104/3/626.long Pfreundschuh et al. 2004 (NHL-B1)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00cd00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |CHOEP-14<br> CHOEP-21<br> [[Diffuse_large_B-cell_lymphoma#CHOP|CHOP]]
 |-
 |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2808%2970002-0/fulltext Pfreundschuh et al. 2008 (RICOVER-60)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00cd00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Diffuse_large_B-cell_lymphoma#R-CHOP_Intensified|R-CHOP-14]]
 |-
 |}
+''Treatment preceded by [[#Vincristine_.26_Prednisone|pre-phase vincristine & prednisone]] (recommended in '''NHL-B1''' and mandatory in '''RICOVER-60''').''
-====Pre-phase treatment====
+====Chemotherapy====
-''Recommended in Pfreundschuh et al. 2004, but mandatory in Pfreundschuh et al. 2008 "to improve the performance status of patients and to ameliorate side-effects of the first chemotherapy cycle." A difference was that the prednisone in Pfreundschuh et al. 2004 could be given for 5 to 7 days.''
-*[[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''', then proceed to main CHOP-14 regimen
-====Main CHOP-14 regimen====
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 *[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
@@ Line 412: / Line 371: @@
 ===References===
-# Blayney DW, LeBlanc ML, Grogan T, Gaynor ER, Chapman RA, Spiridonidis CH, Taylor SA, Bearman SI, Miller TP, Fisher RI; Southwest Oncology Group. Dose-intense chemotherapy every 2 weeks with dose-intense cyclophosphamide, doxorubicin, vincristine, and prednisone may improve survival in intermediate- and high-grade lymphoma: a phase II study of the Southwest Oncology Group (SWOG 9349). J Clin Oncol. 2003 Jul 1;21(13):2466-73. [http://jco.ascopubs.org/content/21/13/2466.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12829664 PubMed]
+# Blayney DW, LeBlanc ML, Grogan T, Gaynor ER, Chapman RA, Spiridonidis CH, Taylor SA, Bearman SI, Miller TP, Fisher RI; Southwest Oncology Group. Dose-intense chemotherapy every 2 weeks with dose-intense cyclophosphamide, doxorubicin, vincristine, and prednisone may improve survival in intermediate- and high-grade lymphoma: a phase II study of the Southwest Oncology Group (SWOG 9349). J Clin Oncol. 2003 Jul 1;21(13):2466-73. [http://jco.ascopubs.org/content/21/13/2466.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12829664 PubMed]
-# 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://bloodjournal.hematologylibrary.org/content/104/3/626.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/14982884 PubMed]
+# 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://bloodjournal.hematologylibrary.org/content/104/3/626.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14982884 PubMed]
-# 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://bloodjournal.hematologylibrary.org/content/104/3/634.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15016643 PubMed]
+# 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://bloodjournal.hematologylibrary.org/content/104/3/634.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15016643 PubMed]
 <!-- Presented orally and in abstract form at the 47th annual meeting of the American Society of Hematology, Atlanta, Georgia, December 11, 2005. -->
-# Verdonck LF, Notenboom A, de Jong DD, MacKenzie MA, Verhoef GE, Kramer MH, Ossenkoppele GJ, Doorduijn JK, Sonneveld P, van Imhoff GW. Intensified 12-week CHOP (I-CHOP) plus G-CSF compared with standard 24-week CHOP (CHOP-21) for patients with intermediate-risk aggressive non-Hodgkin lymphoma: a phase 3 trial of the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON). Blood. 2007 Apr 1;109(7):2759-66. [http://bloodjournal.hematologylibrary.org/content/109/7/2759.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17132720 PubMed]
+# Verdonck LF, Notenboom A, de Jong DD, MacKenzie MA, Verhoef GE, Kramer MH, Ossenkoppele GJ, Doorduijn JK, Sonneveld P, van Imhoff GW. Intensified 12-week CHOP (I-CHOP) plus G-CSF compared with standard 24-week CHOP (CHOP-21) for patients with intermediate-risk aggressive non-Hodgkin lymphoma: a phase 3 trial of the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON). Blood. 2007 Apr 1;109(7):2759-66. [http://bloodjournal.hematologylibrary.org/content/109/7/2759.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17132720 PubMed]
-# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2808%2970002-0/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18226581 PubMed]
+# 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. [http://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]
 ==CHOP Modified {{#subobject:bb947|Regimen=1}}==
@@ Line 434: / Line 393: @@
 |-
 |[http://annonc.oxfordjournals.org/content/14/2/258.long Bessell et al. 2003]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Diffuse_large_B-cell_lymphoma#CNOP.2C_MCOP|MCOP]]
-|<span
+|style="background-color:#eeee00"|Seems not superior
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Seems not superior</span>
 |-
 |}
@@ Line 459: / Line 408: @@
 ===References===
-# Bessell EM, Burton A, Haynes AP, Glaholm J, Child JA, Cullen MH, Davies JM, Smith GM, Ellis IO, Jack A, Jones EL; Central Lymphoma Group UK. A randomised multicentre trial of modified CHOP versus MCOP in patients aged 65 years and over with aggressive non-Hodgkin's lymphoma. Ann Oncol. 2003 Feb;14(2):258-67. [http://annonc.oxfordjournals.org/content/14/2/258.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12562653 PubMed]
+# Bessell EM, Burton A, Haynes AP, Glaholm J, Child JA, Cullen MH, Davies JM, Smith GM, Ellis IO, Jack A, Jones EL; Central Lymphoma Group UK. A randomised multicentre trial of modified CHOP versus MCOP in patients aged 65 years and over with aggressive non-Hodgkin's lymphoma. Ann Oncol. 2003 Feb;14(2):258-67. [http://annonc.oxfordjournals.org/content/14/2/258.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12562653 PubMed]
 ==CNOP; MCOP {{#subobject:3121b4|Regimen=1}}==
@@ Line 476: / Line 425: @@
 |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1971727/ Sonneveld et al. 1990]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1971727/ Sonneveld et al. 1990]
 |style="background-color:#eeee00"|Phase II
 |style="background-color:#d3d3d3"|
@@ Line 484: / Line 433: @@
 |style="background-color:#00cd00"|Phase III
 |[[Diffuse_large_B-cell_lymphoma#CHOP|CHOP]]
-|
+|style="background-color:#eeee00"|Seems not superior
 |-
 |[http://annonc.oxfordjournals.org/content/14/2/258.long Bessell et al. 2003]
@@ Line 501: / Line 450: @@
 ===References===
-# Sonneveld P, Michiels JJ. Full dose chemotherapy in elderly patients with non-Hodgkin's lymphoma: a feasibility study using a mitoxantrone containing regimen. Br J Cancer. 1990 Jul;62(1):105-8. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1971727/ link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/2390469 PubMed]
+# Sonneveld P, Michiels JJ. Full dose chemotherapy in elderly patients with non-Hodgkin's lymphoma: a feasibility study using a mitoxantrone containing regimen. Br J Cancer. 1990 Jul;62(1):105-8. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1971727/ link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2390469 PubMed]
-# Pavlovsky S, Santarelli MT, Erazo A, Diaz Maqueo JC, Somoza N, Lluesma Goñalons M, Cervantes G, Garcia Vela EL, Corrado C, Magnasco H, et al. Results of a randomized study of previously-untreated intermediate and high grade lymphoma using CHOP versus CNOP. Ann Oncol. 1992 Mar;3(3):205-9. [http://annonc.oxfordjournals.org/content/3/3/205.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/1586618 PubMed]
+# Pavlovsky S, Santarelli MT, Erazo A, Diaz Maqueo JC, Somoza N, Lluesma Goñalons M, Cervantes G, Garcia Vela EL, Corrado C, Magnasco H, et al. Results of a randomized study of previously-untreated intermediate and high grade lymphoma using CHOP versus CNOP. Ann Oncol. 1992 Mar;3(3):205-9. [http://annonc.oxfordjournals.org/content/3/3/205.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/1586618 PubMed]
-# Bessell EM, Burton A, Haynes AP, Glaholm J, Child JA, Cullen MH, Davies JM, Smith GM, Ellis IO, Jack A, Jones EL; Central Lymphoma Group UK. A randomised multicentre trial of modified CHOP versus MCOP in patients aged 65 years and over with aggressive non-Hodgkin's lymphoma. Ann Oncol. 2003 Feb;14(2):258-67. [http://annonc.oxfordjournals.org/content/14/2/258.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12562653 PubMed]
+# Bessell EM, Burton A, Haynes AP, Glaholm J, Child JA, Cullen MH, Davies JM, Smith GM, Ellis IO, Jack A, Jones EL; Central Lymphoma Group UK. A randomised multicentre trial of modified CHOP versus MCOP in patients aged 65 years and over with aggressive non-Hodgkin's lymphoma. Ann Oncol. 2003 Feb;14(2):258-67. [http://annonc.oxfordjournals.org/content/14/2/258.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12562653 PubMed]
 ==R-CHOEP-14 {{#subobject:75c24e|Regimen=1}}==
@@ Line 521: / Line 470: @@
 |-
 |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70481-3/fulltext Schmitz et al. 2012 (DSHNHL 2002-1)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |R-MegaCHOEP
-|<span
+|style="background-color:#eeee00"|Seems not superior
-style="background:#EEEE00;
+|style="background-color:#00cd00"|Decreased toxicity
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Seems not superior</span>
-|<span
-style="background:#00cd00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Decreased toxicity</span>
 |-
 |}
@@ Line 561: / Line 495: @@
 |-
 |[http://annonc.oxfordjournals.org/content/24/5/1385.long Holte et al. 2013]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 603: / Line 532: @@
 ===References===
-# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70481-3/fulltext link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/23168367 PubMed]
+# 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. [http://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]
-# 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''' [http://www.ncbi.nlm.nih.gov/pubmed/23247661 PubMed]
+# 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 666: / Line 595: @@
 |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616024/ Offner et al. 2015]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616024/ Offner et al. 2015]
 |style="background-color:#00cd00"|Randomized Phase II
 |VR-CAP
@@ Line 855: / Line 784: @@
 ===References===
-# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa011795 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11807147 PubMed]
+# 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. [http://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:''' 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''' [http://www.ncbi.nlm.nih.gov/pubmed/15867204 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]
-## '''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://bloodjournal.hematologylibrary.org/content/116/12/2040.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20548096 PubMed] content property of [http://hemonc.org HemOnc.org]
+## '''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://bloodjournal.hematologylibrary.org/content/116/12/2040.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20548096 PubMed] content property of [http://hemonc.org HemOnc.org]
-## '''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] [http://www.ncbi.nlm.nih.gov/pubmed/22301063 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]
-# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2806%2970664-7/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16648042 PubMed]
+# 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. [http://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:''' 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2811%2970235-2/fulltext link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21940214 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. [http://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]
-# 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''' [http://www.ncbi.nlm.nih.gov/pubmed/16754935 PubMed]
+# 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]
-# 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''' [http://www.ncbi.nlm.nih.gov/pubmed/18413640 PubMed]
+# 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]
-## '''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] [http://www.ncbi.nlm.nih.gov/pubmed/27382104 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/pubmed/27382104 PubMed]
-# 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''' [http://www.ncbi.nlm.nih.gov/pubmed/21646602 PubMed]
+# 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]
-# 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. [http://informahealthcare.com/doi/full/10.3109/10428194.2011.621565 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21895543 PubMed]
+# 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. [http://informahealthcare.com/doi/full/10.3109/10428194.2011.621565 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21895543 PubMed]
-# 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. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61040-4/fulltext link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/22118442 PubMed]
+# 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. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61040-4/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22118442 PubMed]
-# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70122-0/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23578722 PubMed]
+# 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. [http://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]
-# 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. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)60313-X/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23615461 PubMed]
+# 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. [http://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]
-# 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.12585/full link to original article] '''contains verified protocol''' [http://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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.12585/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24117234 PubMed]
-# 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] [http://www.ncbi.nlm.nih.gov/pubmed/24895339 PubMed]
+# 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/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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.13463/full link to original article] [http://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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.13463/full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25907897 PubMed]
-# 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] [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616024/ link to PMC article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/26232170 PubMed]
+# 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] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616024/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26232170 PubMed]
-# 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. [http://www.sciencedirect.com/science/article/pii/S0959804916000885 link to original article] '''does not contain protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/2699093 PubMed]
+# 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. [http://www.sciencedirect.com/science/article/pii/S0959804916000885 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/2699093 PubMed]
-# 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.14100/abstract link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/27072903 PubMed]
+# 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.14100/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27072903 PubMed]
 ==R-CHOP Intensified {{#subobject:fc3bde|Regimen=1}}==
@@ Line 895: / Line 824: @@
 |-
 |[http://meetinglibrary.asco.org/content/133133-144 Pfreundschuh et al. 2014 (SEXIE-R-CHOP-14)]
-|<span
+|style="background-color:#00cd00"|Randomized Phase II
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Randomized Phase II</span>
 |See below
 |-
 |}
 ====Main CHOP-14 portion====
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 927: / Line 850: @@
 |-
 |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70122-0/fulltext Delarue et al. 2013 (LNH03-6B)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Diffuse_large_B-cell_lymphoma#R-CHOP|R-CHOP21]]
-|<span
+|style="background-color:#eeee00"|Seems not superior
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Seems not superior</span>
 |-
 |}
@@ Line 965: / Line 878: @@
 |-
 |[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)60313-X/fulltext Cunningham et al. 2013]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Diffuse_large_B-cell_lymphoma#R-CHOP|R-CHOP-21]]
-|<span
+|style="background-color:#eeee00"|Seems not superior
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Seems not superior</span>
 |-
 |}
@@ Line 1,011: / Line 914: @@
 |-
 |rowspan=2 |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2808%2970002-0/fulltext Pfreundschuh et al. 2008 (RICOVER-60)]
-|rowspan=2 |<span
+|rowspan=2 style="background-color:#00cd00"|Phase III
-style="background:#00cd00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Diffuse_large_B-cell_lymphoma#CHOP_Intensified|CHOP-14 x 6]]
-|<span
+|style="background-color:#00cd00"|Superior OS
-style="background:#00cd00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Superior OS</span>
 |-
 |[[Diffuse_large_B-cell_lymphoma#CHOP_Intensified|CHOP-14 x 8]]<br> R-CHOP-14 x 8
@@ Line 1,029: / Line 922: @@
 |-
 |}
+''Treatment preceded by [[#Vincristine_.26_Prednisone|pre-phase vincristine & prednisone]].''
-====Pre-phase treatment====
+====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''', then proceed to main R-CHOP-14 regimen
-====Main regimen====
 *[[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 1,060: / Line 947: @@
 |-
 |[http://jco.ascopubs.org/content/32/36/4127.full Pfreundschuh et al. 2014 (SMARTE-R-CHOP-14)]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
+''Treatment preceded by [[#Vincristine_.26_Prednisone|pre-phase vincristine & prednisone]].''
-====Pre-phase treatment====
+===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''', then proceed to main SMARTE-R-CHOP-14 regimen
-====Main regimen====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on days -4, 0, 10, 29, 57, 99, 155, and 239 (independent of CHOP cycles)
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 1,094: / Line 970: @@
 ===References===
-# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2808%2970002-0/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18226581 PubMed]
+# 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. [http://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]
-# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70122-0/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23578722 PubMed]
+# 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. [http://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]
-# 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. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)60313-X/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23615461 PubMed]
+# 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. [http://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]
 # '''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]
-# 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''' [http://www.ncbi.nlm.nih.gov/pubmed/25403207 PubMed]
+# 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]
 ==R-CVP {{#subobject:1b5df7|Regimen=1}}==
@@ Line 1,138: / Line 1,014: @@
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1111/bjh.12585/full Oki et al. 2013]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Diffuse_large_B-cell_lymphoma#R-CHOP|R-CHOP]]
-|<span
+|style="background-color:#00cd00"|Seems to have increased CRR
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Seems to have increased CRR</span>
 |-
 |}
@@ Line 1,200: / Line 1,066: @@
 ===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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.12585/full link to original article] '''contains verified protocol''' [http://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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.12585/full link to original article] '''contains verified protocol''' [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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.13463/full link to original article] [http://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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.13463/full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25907897 PubMed]
 ==R-miniCEOP {{#subobject:cd6200|Regimen=1}}==
@@ Line 1,219: / Line 1,085: @@
 |-
 |[http://informahealthcare.com/doi/full/10.3109/10428194.2011.621565 Merli et al. 2012 (ANZINTER3)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Diffuse_large_B-cell_lymphoma#R-CHOP|R-CHOP]]
-|<span
+|style="background-color:#eeee00"|Seems not superior
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Equivalent RR</span>
 |-
 |}
@@ Line 1,254: / Line 1,110: @@
 ===References===
-# 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. [http://informahealthcare.com/doi/full/10.3109/10428194.2011.621565 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21895543 PubMed]
+# 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. [http://informahealthcare.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 1,271: / Line 1,127: @@
 |-
 |[http://www.bloodjournal.org/content/125/2/236.long Persky et al. 2014 (SWOG S0313)]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 1,300: / Line 1,151: @@
 ===References===
-# 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''' [http://www.ncbi.nlm.nih.gov/pubmed/25395425 PubMed]
+# 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/pubmed/25395425 PubMed]
 ==DA-R-EPOCH {{#subobject:ba36e5|Regimen=1}}==
@@ Line 1,319: / Line 1,170: @@
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2006.06438.x/full García-Suárez et al. 2007]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |[http://jco.ascopubs.org/content/26/16/2717.long Wilson et al. 2008]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |[http://www.haematologica.org/content/97/5/758.long Wilson et al. 2012]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1111/bjh.13273/full Purroy et al. 2014]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 1,383: / Line 1,214: @@
 ===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. [http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2006.06438.x/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17233819 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. [http://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] [http://www.ncbi.nlm.nih.gov/pubmed/18378569 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/pubmed/18378569 PubMed]
-# 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] [http://www.ncbi.nlm.nih.gov/pubmed/22133772 PubMed]
+# 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/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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.13273/full link to original article] '''contains protocol''' [http://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. [http://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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.13463/full link to original article] [http://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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.13463/full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25907897 PubMed]
 ==Helicobacter pylori eradication therapy {{#subobject:be3ef5|Regimen=1}}==
@@ Line 1,412: / Line 1,243: @@
 ===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; quiz 5057. Epub 2012 Mar 7. [http://bloodjournal.hematologylibrary.org/content/119/21/4838.long link to original article] [http://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; quiz 5057. Epub 2012 Mar 7. [http://bloodjournal.hematologylibrary.org/content/119/21/4838.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22403257 PubMed]
 ==R-BL {{#subobject:fe578a|Regimen=1}}==
@@ Line 1,428: / Line 1,259: @@
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1111/bjh.14049/abstract Hitz et al. 2016 (SAKK 38/08)]
-|<span
+|style="background-color:#eeee00"|Phase II, <20 pts in subgroup
-style="background:#ff0000;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II, <20 pts in this subgroup</span>
 |61% (95% CI 45-76%)
 |-
@@ Line 1,445: / Line 1,271: @@
 ===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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.14049/abstract link to original article] '''contains protocol''' [http://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. [http://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; DRCOP {{#subobject:bdf229|Regimen=1}}==
@@ Line 1,461: / Line 1,287: @@
 |-
 |[http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(14)00411-X/fulltext Oki et al. 2014]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 1,497: / Line 1,318: @@
 |-
 |[http://informahealthcare.com/doi/full/10.1080/10428190600799946 Zaja et al. 2006]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 1,517: / Line 1,333: @@
 ===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. [http://informahealthcare.com/doi/full/10.1080/10428190600799946 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/17071492 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. [http://informahealthcare.com/doi/full/10.1080/10428190600799946 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17071492 PubMed]
-# 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] [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4344896/ link to PMC article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/25445468 PubMed]
+# 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] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4344896/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25445468 PubMed]
 ==R-CEOP90 (Epirubicin) {{#subobject:ebcd7e|Regimen=1}}==
@@ Line 1,533: / Line 1,349: @@
 |-
 |[http://informahealthcare.com/doi/full/10.3109/10428194.2013.876632 Cai et al. 2014]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 1,553: / Line 1,364: @@
 ===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. [http://informahealthcare.com/doi/full/10.3109/10428194.2013.876632 link to original article] '''contains verified protocol''' [http://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. [http://informahealthcare.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 1,568: / Line 1,379: @@
 |-
 |[http://abstracts.hematologylibrary.org/cgi/content/abstract/114/22/408 Moccia et al. 2009]
-|<span
+|style="background-color:#ff0000"|Retrospective
-style="background:#ff0000;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Retrospective</span>
 |-
 |}
@@ Line 1,604: / Line 1,410: @@
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1111/bjh.12446/full Hagemeister et al. 2013]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 1,622: / Line 1,423: @@
 ===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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.12446/full link to original article] '''contains verified protocol''' [http://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. [http://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-CHOP -> Ibritumomab tiuxetan {{#subobject:7ef887|Regimen=1}}==
@@ Line 1,637: / Line 1,438: @@
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1111/bjh.13493/full Witzig et al. 2015 (ECOG3402)]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 1,664: / Line 1,460: @@
 ===References===
-# 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.13493/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/25974212 PubMed]
+# 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.13493/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25974212 PubMed]
 ==R-GCVP {{#subobject:dff264|Regimen=1}}==
@@ Line 1,679: / Line 1,475: @@
 |-
 |[http://jco.ascopubs.org/content/32/4/282.full Fields et al. 2013]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 1,711: / Line 1,502: @@
 ===References===
 <!-- Presented at the 53rd Annual Meeting of the American Society of Hematology, San Diego, CA, December 10-13, 2011. -->
-# Fields PA, Townsend W, Webb A, Counsell N, Pocock C, Smith P, Jack A, El-Mehidi N, Johnson PW, Radford J, Linch DC, Cunnningham 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''' [http://www.ncbi.nlm.nih.gov/pubmed/24220559 PubMed]
+# Fields PA, Townsend W, Webb A, Counsell N, Pocock C, Smith P, Jack A, El-Mehidi N, Johnson PW, Radford J, Linch DC, Cunnningham 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 1,726: / Line 1,517: @@
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1111/bjh.13036/full Pardal et al. 2014]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 1,749: / Line 1,535: @@
 ===References===
-# 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.13036/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/25066542 PubMed]
+# 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. [http://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 1,764: / Line 1,550: @@
 |-
 |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70069-9/fulltext Peyrade et al. 2011]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 1,789: / Line 1,570: @@
 ===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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70069-9/fulltext link to original article] '''contains verified protocol''' [http://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. [http://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; LR-CHOP-21 {{#subobject:2a4e31|Regimen=1}}==
@@ Line 1,805: / Line 1,586: @@
 |-
 |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70191-3/fulltext Vitolo et al. 2014 (REAL07)]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 1,839: / Line 1,615: @@
 |-
 |[http://jco.ascopubs.org/content/33/3/251.full Nowakowski et al. 2014]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 1,867: / Line 1,638: @@
 |-
 |[http://www.haematologica.org/content/98/11/1732 Chiappella et al. 2013]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 1,892: / Line 1,658: @@
 ===References===
-# Nowakowski GS, LaPlant B, Habermann TM, Rivera CE, Macon WR, Inwards DJ, Micallef IN, Johnston PB, Porrata LF, Ansell SM, Klebig RR, Reeder CB, Witzig TE. Lenalidomide can be safely combined with R-CHOP (R2CHOP) in the initial chemotherapy for aggressive B-cell lymphomas: phase I study. Leukemia. 2011 Dec;25(12):1877-81. Epub 2011 Jul 1. [http://www.nature.com/leu/journal/v25/n12/full/leu2011165a.html link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21720383 PubMed]
+# Nowakowski GS, LaPlant B, Habermann TM, Rivera CE, Macon WR, Inwards DJ, Micallef IN, Johnston PB, Porrata LF, Ansell SM, Klebig RR, Reeder CB, Witzig TE. Lenalidomide can be safely combined with R-CHOP (R2CHOP) in the initial chemotherapy for aggressive B-cell lymphomas: phase I study. Leukemia. 2011 Dec;25(12):1877-81. Epub 2011 Jul 1. [http://www.nature.com/leu/journal/v25/n12/full/leu2011165a.html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21720383 PubMed]
-# 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''' [http://www.ncbi.nlm.nih.gov/pubmed/23812930 PubMed]
+# 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/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]. -->
-# 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; on behalf of the 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70191-3/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24831981 PubMed]
+# 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; on behalf of the 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. [http://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] -->
-# 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''' [http://www.ncbi.nlm.nih.gov/pubmed/25135992 PubMed]
+# 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]
 ==VR-CHOP {{#subobject:477a16|Regimen=1}}==
@@ Line 1,913: / Line 1,679: @@
 |-
 |[http://jco.ascopubs.org/content/29/6/690.long Ruan et al. 2010]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 1,937: / Line 1,698: @@
 ===References===
-# Ruan J, Martin P, Furman RR, Lee SM, Cheung K, Vose JM, Lacasce A, Morrison J, Elstrom R, Ely S, Chadburn A, Cesarman E, Coleman M, Leonard JP. Bortezomib plus CHOP-rituximab for previously untreated diffuse large B-cell lymphoma and mantle cell lymphoma. J Clin Oncol. 2011 Feb 20;29(6):690-7. Epub 2010 Dec 28. [http://jco.ascopubs.org/content/29/6/690.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21189393 PubMed]
+# Ruan J, Martin P, Furman RR, Lee SM, Cheung K, Vose JM, Lacasce A, Morrison J, Elstrom R, Ely S, Chadburn A, Cesarman E, Coleman M, Leonard JP. Bortezomib plus CHOP-rituximab for previously untreated diffuse large B-cell lymphoma and mantle cell lymphoma. J Clin Oncol. 2011 Feb 20;29(6):690-7. Epub 2010 Dec 28. [http://jco.ascopubs.org/content/29/6/690.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21189393 PubMed]
 =Consolidation and/or maintenance after upfront therapy=
-==Autologous stem cell transplant {{#subobject:fccfc5|Regimen=1}}==
+==Autologous hematopoietic cell transplant {{#subobject:fccfc5|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
@@ Line 1,961: / Line 1,722: @@
 ===References===
-# 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.14100/abstract link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/27072903 PubMed]
+# 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.14100/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27072903 PubMed]
 ==Cytarabine (Cytosar) {{#subobject:fa5ce3|Regimen=1}}==
@@ Line 1,975: / Line 1,736: @@
 |-
 |[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61040-4/fulltext Récher et al. 2011 (LNH03-2B)]
-|<span
+|style="background-color:#eeee00"|Non-randomized portion of RCT
-style="background:#eeee00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Non-randomized</span>
 |-
 |[http://annonc.oxfordjournals.org/content/24/4/1032.long Ketterer et al. 2013 (LNH03-1B)]
-|<span
+|style="background-color:#eeee00"|Non-randomized
-style="background:#eeee00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Non-randomized</span>
 |-
 |}
@@ Line 1,999: / Line 1,750: @@
 ===References===
-# 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. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61040-4/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22118442 PubMed]
+# 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. [http://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]
-# 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] [http://www.ncbi.nlm.nih.gov/pubmed/23235801 PubMed]
+# 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]
 ==Methotrexate (MTX) {{#subobject:d77e3a|Regimen=1}}==
@@ Line 2,014: / Line 1,765: @@
 |-
 |[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61040-4/fulltext Récher et al. 2011 (LNH03-2B)]
-|<span
+|style="background-color:#eeee00"|Non-randomized portion of RCT
-style="background:#eeee00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Non-randomized</span>
 |-
 |[http://annonc.oxfordjournals.org/content/24/4/1032.long Ketterer et al. 2013 (LNH03-1B)]
-|<span
+|style="background-color:#eeee00"|Non-randomized
-style="background:#eeee00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Non-randomized</span>
 |-
 |}
@@ Line 2,043: / Line 1,784: @@
 ===References===
-# 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. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61040-4/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22118442 PubMed]
+# 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. [http://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]
-# 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] [http://www.ncbi.nlm.nih.gov/pubmed/23235801 PubMed]
+# 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 2,075: / Line 1,816: @@
 |[http://onlinelibrary.wiley.com/doi/10.1111/bjh.14100/abstract Puvvada et al. 2016 (SWOG S9704)]
 |style="background-color:#00cd00"|Phase III
-|[[#Autologous_stem_cell_transplant|AutoHCT]]
+|[[#Autologous_hematopoietic_cell_transplant|AutoHCT]]
 |
 |-
@@ Line 2,082: / Line 1,823: @@
 ===References===
-# 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''' [http://www.ncbi.nlm.nih.gov/pubmed/16754935 PubMed]
+# 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]
-# 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] [http://www.ncbi.nlm.nih.gov/pubmed/19567453 PubMed]
+# 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. -->
-# 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''' [http://www.ncbi.nlm.nih.gov/pubmed/25911553 PubMed]
+# 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/pubmed/25911553 PubMed]
-# 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.13652/full link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/26449739 PubMed]
+# 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.13652/full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26449739 PubMed]
 <!-- 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. -->
-# 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 May 23. [Epub ahead of print] [http://jco.ascopubs.org/content/34/21/2484.full link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/27217449 PubMed]
+# 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 May 23. [Epub ahead of print] [http://jco.ascopubs.org/content/34/21/2484.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27217449 PubMed]
-# 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.14100/abstract link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/27072903 PubMed]
+# 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.14100/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27072903 PubMed]
 ==REI {{#subobject:62de3a|Regimen=1}}==
@@ Line 2,104: / Line 1,845: @@
 |-
 |[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61040-4/fulltext Récher et al. 2011 (LNH03-2B)]
-|<span
+|style="background-color:#eeee00"|Non-randomized portion of RCT
-style="background:#eeee00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Non-randomized</span>
 |-
 |[http://annonc.oxfordjournals.org/content/24/4/1032.long Ketterer et al. 2013 (LNH03-1B)]
-|<span
+|style="background-color:#eeee00"|Non-randomized
-style="background:#eeee00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Non-randomized</span>
 |-
 |}
 ''Treatment preceded by [[#Methotrexate_.28MTX.29|methotrexate consolidation]] x 2.''
 ====Chemotherapy====
@@ Line 2,132: / Line 1,862: @@
 ===References===
-# 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. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61040-4/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22118442 PubMed]
+# 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. [http://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]
-# 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] [http://www.ncbi.nlm.nih.gov/pubmed/23235801 PubMed]
+# 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]
 ==Rituximab (Rituxan) {{#subobject:c28fe4|Regimen=1}}==
@@ Line 2,149: / Line 1,879: @@
 |-
 |[http://www.haematologica.org/content/100/7/955 Jaeger et al. 2015 (NHL13)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Diffuse_large_B-cell_lymphoma#Observation|Observation]]
-|<span
+|style="background-color:#eeee00"|Seems not superior
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Seems not superior</span>
 |-
 |}
@@ Line 2,179: / Line 1,899: @@
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1111/bjh.13652/full Witzens-Harig et al. 2015 (HD2002)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[#Observation|Observation]]
-|<span
+|style="background-color:#00cd00"|Superior OS in males
-style="background:#00cd00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Superior OS in males</span>
 |-
 |}
@@ Line 2,202: / Line 1,912: @@
 ===References===
-# 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''' [http://www.ncbi.nlm.nih.gov/pubmed/16754935 PubMed]
+# 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]
-# 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] [http://www.ncbi.nlm.nih.gov/pubmed/19567453 PubMed]
+# 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. -->
-# 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''' [http://www.ncbi.nlm.nih.gov/pubmed/25911553 PubMed]
+# 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/pubmed/25911553 PubMed]
-# 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.13652/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/26449739 PubMed]
+# 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. [http://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/refractory, randomized data=
@@ Line 2,222: / Line 1,932: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://www.bloodjournal.org/content/71/1/117 Velasquez et al. 1988]
 |style="background-color:#eeee00"|Phase II
+|style="background-color:#d3d3d3"|
 |style="background-color:#d3d3d3"|
 |-
@@ Line 2,230: / Line 1,942: @@
 |style="background-color:#00cd00"|Phase III
 |[[Transplant_conditioning_regimens#BEAC|DHAP x 2 -> BEAC]]
+|style="background-color:#ff0000"|Seems to have inferior OS
 |-
 |}
@@ Line 2,245: / Line 1,958: @@
 '''3 to 4 week cycle "according to the extent of myelosuppression"'''
-'''''Velasquez et al. 1988''' report 6 to 10 courses, usually 4 courses beyond maximum response. The '''PARMA''' trial collected bone marrow after cycle 1 and then randomized responders (PR/CR) after cycle 2 to 4 more courses of DHAP versus [[Diffuse_large_B-cell_lymphoma#Autologous_stem_cell_transplant|autologous stem-cell transplant (ASCT)]].''
+'''''Velasquez et al. 1988''' report 6 to 10 courses, usually 4 courses beyond maximum response. The '''PARMA''' trial collected bone marrow after cycle 1 and then randomized responders (PR/CR) after cycle 2 to 4 more courses of DHAP versus [[Diffuse_large_B-cell_lymphoma#Autologous_hematopoietic_cell_transplant|autologous stem-cell transplant (ASCT)]].''
 ===References===
-# Velasquez WS, Cabanillas F, Salvador P, McLaughlin P, Fridrik M, Tucker S, Jagannath S, Hagemeister FB, Redman JR, Swan F, et al. Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP). Blood. 1988 Jan;71(1):117-22. [http://www.bloodjournal.org/content/71/1/117 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/3334893 PubMed]
+# Velasquez WS, Cabanillas F, Salvador P, McLaughlin P, Fridrik M, Tucker S, Jagannath S, Hagemeister FB, Redman JR, Swan F, et al. Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP). Blood. 1988 Jan;71(1):117-22. [http://www.bloodjournal.org/content/71/1/117 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/3334893 PubMed]
-# Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, et al. 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. [http://www.nejm.org/doi/full/10.1056/NEJM199512073332305 link to original article] '''does not contain protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/7477169 PubMed]
+# Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, et al. 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. [http://www.nejm.org/doi/full/10.1056/NEJM199512073332305 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/7477169 PubMed]
 ==ESHAP {{#subobject:4c0082|Regimen=1}}==
@@ Line 2,289: / Line 2,002: @@
 ===References===
-# Velasquez WS, McLaughlin P, Tucker S, Hagemeister FB, Swan F, Rodriguez MA, Romaguera J, Rubenstein E, Cabanillas F. ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. J Clin Oncol. 1994 Jun;12(6):1169-76. [http://jco.ascopubs.org/content/12/6/1169.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/8201379 PubMed]
+# Velasquez WS, McLaughlin P, Tucker S, Hagemeister FB, Swan F, Rodriguez MA, Romaguera J, Rubenstein E, Cabanillas F. ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. J Clin Oncol. 1994 Jun;12(6):1169-76. [http://jco.ascopubs.org/content/12/6/1169.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8201379 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] [http://www.ncbi.nlm.nih.gov/pubmed/20371445 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]
 ==Gemcitabine (Gemzar) {{#subobject:df3421|Regimen=1}}==
@@ Line 2,321: / Line 2,034: @@
 ===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''' [http://www.ncbi.nlm.nih.gov/pubmed/10577850 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]
-# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70212-7/abstract link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22652183 PubMed]
+# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70212-7/abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22652183 PubMed]
 ==Ifosfamide (Ifex) {{#subobject:b9a669|Regimen=1}}==
@@ Line 2,335: / Line 2,048: @@
 |'''Comparator'''
 |-
-|[http://www.ncbi.nlm.nih.gov/pubmed/1743622 Case et al. 1991 (CALGB 8552)]
+|[https://www.ncbi.nlm.nih.gov/pubmed/1743622 Case et al. 1991 (CALGB 8552)]
 |style="background-color:#eeee00"|Phase II
 |style="background-color:#d3d3d3"|
@@ Line 2,355: / Line 2,068: @@
 ===References===
-# 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. [http://www.ncbi.nlm.nih.gov/pubmed/1743622 PubMed]
+# 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. Review. [http://informahealthcare.com/doi/abs/10.1080/10428190290021632 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/12148908 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. Review. [http://informahealthcare.com/doi/abs/10.1080/10428190290021632 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12148908 PubMed]
-# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70212-7/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22652183 PubMed]
+# 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. [http://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]
 ==Oxaliplatin (Eloxatin) {{#subobject:308526|Regimen=1}}==
@@ Line 2,392: / Line 2,105: @@
 ===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''' [http://www.ncbi.nlm.nih.gov/pubmed/10355582 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]
-# '''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. Review. [http://informahealthcare.com/doi/abs/10.1080/10428190290021632 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/12148908 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. Review. [http://informahealthcare.com/doi/abs/10.1080/10428190290021632 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12148908 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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.21219/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15973667 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. [http://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]
-# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70212-7/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22652183 PubMed]
+# 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. [http://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]
 ==Panobinostat (Farydak) {{#subobject:6b0341|Regimen=1}}==
@@ Line 2,427: / Line 2,140: @@
 ===References===
-# 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''' [http://www.ncbi.nlm.nih.gov/pubmed/27166360 PubMed]
+# 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/pubmed/27166360 PubMed]
 ==Panobinostat & Rituximab {{#subobject:f7bdff|Regimen=1}}==
@@ Line 2,460: / Line 2,173: @@
 ===References===
-# 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''' [http://www.ncbi.nlm.nih.gov/pubmed/27166360 PubMed]
+# 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/pubmed/27166360 PubMed]
 ==Pixantrone (Pixuvri) {{#subobject:bedd78|Regimen=1}}==
@@ Line 2,486: / Line 2,199: @@
 ===References===
-# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70212-7/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22652183 PubMed]
+# 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. [http://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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.14101/abstract link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/27118109 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.14101/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27118109 PubMed]
 ==R-DHAP {{#subobject:18c266|Regimen=1}}==
@@ Line 2,506: / Line 2,219: @@
 |style="background-color:#00cd00"|Phase III
 |[[Diffuse_large_B-cell_lymphoma#R-GDP|R-GDP]]
-|style="background-color:#eeee00"|Noninferior RR
+|style="background-color:#eeee00"|Seems non-inferior
 |-
 |}
@@ Line 2,517: / Line 2,230: @@
 '''21-day cycle for up to 3 cycles'''
-''Responders proceeded to stem-cell mobilization and [[Diffuse_large_B-cell_lymphoma#Autologous_stem_cell_transplant|autologous stem cell transplant]].''
+''Responders proceeded to stem-cell mobilization and [[Diffuse_large_B-cell_lymphoma#Autologous_hematopoietic_cell_transplant|autologous hematopoietic cell transplant]].''
 ===Regimen #2 {{#subobject:af0858|Variant=1}}===
@@ Line 2,547: / Line 2,260: @@
 '''21-day cycle for 3 cycles'''
-''Patients with complete or partial response then received [[Diffuse_large_B-cell_lymphoma#Autologous_stem_cell_transplant|BEAM -> autologous stem-cell transplant]].''
+''Patients with complete or partial response then received [[Diffuse_large_B-cell_lymphoma#Autologous_hematopoietic_cell_transplant|BEAM -> autologous stem-cell transplant]].''
 ===References===
-# 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] [http://www.ncbi.nlm.nih.gov/pubmed/16702182 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''' [http://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/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. -->
-# 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''' [http://www.ncbi.nlm.nih.gov/pubmed/25267740 PubMed]
+# 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-ESHAP {{#subobject:7794d|Regimen=1}}==
@@ Line 2,598: / Line 2,311: @@
 ===References===
-# Velasquez WS, McLaughlin P, Tucker S, Hagemeister FB, Swan F, Rodriguez MA, Romaguera J, Rubenstein E, Cabanillas F. ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. J Clin Oncol. 1994 Jun;12(6):1169-76. [http://jco.ascopubs.org/content/12/6/1169.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/8201379 PubMed]
+# Velasquez WS, McLaughlin P, Tucker S, Hagemeister FB, Swan F, Rodriguez MA, Romaguera J, Rubenstein E, Cabanillas F. ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. J Clin Oncol. 1994 Jun;12(6):1169-76. [http://jco.ascopubs.org/content/12/6/1169.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8201379 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''' [http://www.ncbi.nlm.nih.gov/pubmed/18945747 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] [http://www.ncbi.nlm.nih.gov/pubmed/20371445 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 2,619: / Line 2,332: @@
 |style="background-color:#00cd00"|Phase III
 |[[Diffuse_large_B-cell_lymphoma#R-DHAP|R-DHAP]]
-|style="background-color:#eeee00"|Noninferior RR
+|style="background-color:#eeee00"|Seems non-inferior
 |-
 |}
@@ Line 2,630: / Line 2,343: @@
 '''21-day cycle for up to 3 cycles'''
-''Responders proceeded to stem-cell mobilization and [[Diffuse_large_B-cell_lymphoma#Autologous_stem_cell_transplant|autologous stem cell transplant]].''
+''Responders proceeded to stem-cell mobilization and [[Diffuse_large_B-cell_lymphoma#Autologous_hematopoietic_cell_transplant|autologous hematopoietic cell transplant]].''
 ===References===
-# 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''' [http://www.ncbi.nlm.nih.gov/pubmed/25267740 PubMed]
+# 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 2,671: / Line 2,384: @@
 '''21-day cycle for 3 cycles'''
-''Patients with complete or partial response then received [[Diffuse_large_B-cell_lymphoma#Autologous_stem_cell_transplant|BEAM autologous stem-cell transplant]].''
+''Patients with complete or partial response then received [[Diffuse_large_B-cell_lymphoma#Autologous_hematopoietic_cell_transplant|BEAM autologous stem-cell transplant]].''
 ===References===
-<!-- # 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] [http://www.ncbi.nlm.nih.gov/pubmed/16702182 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''' [http://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/pubmed/20660832 PubMed]
-# 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] [http://www.ncbi.nlm.nih.gov/pubmed/25651427 PubMed]
+# 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]
 ==Vinorelbine (Navelbine) {{#subobject:29c647|Regimen=1}}==
@@ Line 2,706: / Line 2,419: @@
 ===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''' [http://www.ncbi.nlm.nih.gov/pubmed/9006750 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]
-# '''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. Review. [http://informahealthcare.com/doi/abs/10.1080/10428190290021632 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/12148908 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. Review. [http://informahealthcare.com/doi/abs/10.1080/10428190290021632 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12148908 PubMed]
-# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70212-7/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22652183 PubMed]
+# 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. [http://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]
 =Relapsed/refractory, non-randomized or retrospective data=
@@ Line 2,724: / Line 2,437: @@
 |-
 |[http://www.bloodjournal.org/content/127/11/1410.long Viardot et al. 2016]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 2,750: / Line 2,458: @@
 ===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). -->
-# 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''' [http://www.ncbi.nlm.nih.gov/pubmed/26755709 PubMed]
+# 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/pubmed/26755709 PubMed]
 ==BR {{#subobject:1bb486|Regimen=1}}==
@@ Line 2,765: / Line 2,473: @@
 |-
 |[http://jco.ascopubs.org/content/31/17/2103.full Ohmachi et al. 2013]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |[http://link.springer.com/article/10.1007%2Fs00277-013-1879-x/fulltext.html Vacirca et al. 2013]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 2,795: / Line 2,493: @@
 ===References===
 <!-- Presented at the 48th Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2012, Chicago, IL. -->
-# 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''' [http://www.ncbi.nlm.nih.gov/pubmed/23650408 PubMed]
+# 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]
-# 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''' [http://www.ncbi.nlm.nih.gov/pubmed/23955074 PubMed]
+# 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/pubmed/23955074 PubMed]
 ==Brentuximab vedotin (Adcetris) {{#subobject:d4dff2|Regimen=1}}==
@@ Line 2,810: / Line 2,508: @@
 |-
 |[https://ash.confex.com/ash/2014/webprogram/Paper67042.html Bartlett et al. 2014]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |[http://www.bloodjournal.org/content/125/9/1394 Jacobsen et al. 2015]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 2,835: / Line 2,523: @@
 # '''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]
 <!-- '''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] -->
-# 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''' [http://www.ncbi.nlm.nih.gov/pubmed/25573987 PubMed]
+# 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]
 ==EPOCH {{#subobject:eca645|Regimen=1}}==
@@ Line 2,854: / Line 2,542: @@
 |-
 |[http://jco.ascopubs.org/content/11/8/1573.long Wilson et al. 1993]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 2,879: / Line 2,562: @@
 ===References===
-# Wilson WH, Bryant G, Bates S, Fojo A, Wittes RE, Steinberg SM, Kohler DR, Jaffe ES, Herdt J, Cheson BD et al. EPOCH chemotherapy: toxicity and efficacy in relapsed and refractory non-Hodgkin's lymphoma. J Clin Oncol. 1993 Aug;11(8):1573-82 [http://jco.ascopubs.org/content/11/8/1573.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/7687667 PubMed]
+# Wilson WH, Bryant G, Bates S, Fojo A, Wittes RE, Steinberg SM, Kohler DR, Jaffe ES, Herdt J, Cheson BD et al. EPOCH chemotherapy: toxicity and efficacy in relapsed and refractory non-Hodgkin's lymphoma. J Clin Oncol. 1993 Aug;11(8):1573-82 [http://jco.ascopubs.org/content/11/8/1573.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/7687667 PubMed]
 ==Everolimus (Afinitor) {{#subobject:fb3cbd|Regimen=1}}==
@@ Line 2,892: / Line 2,575: @@
 |-
 |[http://www.nature.com/leu/journal/v25/n2/full/leu2010226a.html Witzig et al. 2011]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 2,909: / Line 2,587: @@
 ===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. [http://www.nature.com/leu/journal/v25/n2/full/leu2010226a.html link to original article] '''contains verified protocol''' [http://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. [http://www.nature.com/leu/journal/v25/n2/full/leu2010226a.html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21135857 PubMed]
 ==Everolimus & Rituximab {{#subobject:bae86f|Regimen=1}}==
@@ Line 2,923: / Line 2,601: @@
 |-
 |[http://www.haematologica.org/content/98/4/615.long Barnes et al. 2013]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 2,939: / Line 2,612: @@
 ===References===
-# 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''' [http://www.ncbi.nlm.nih.gov/pubmed/23144193 PubMed]
+# 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/pubmed/23144193 PubMed]
 ==GVD {{#subobject:7102c5|Regimen=1}}==
@@ Line 2,954: / Line 2,627: @@
 |-
 |[http://link.springer.com/article/10.1007%2Fs12032-012-0350-5 Bai et al. 2013]
-|<span
+|style="background-color:#ff0000"|Retrospective
-style="background:#ff0000;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Retrospective</span>
 |-
 |}
@@ Line 2,970: / Line 2,638: @@
 ===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''' [http://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 (Zevalin) {{#subobject:0b97a2|Regimen=1}}==
@@ Line 2,983: / Line 2,651: @@
 ===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] [http://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 (Imbruvica) {{#subobject:ba5ba9|Regimen=1}}==
@@ Line 2,997: / Line 2,665: @@
 |-
 |[https://ash.confex.com/ash/2012/webprogram/Paper48270.html Wilson et al. 2012]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 3,028: / Line 2,691: @@
 |-
 |[http://annonc.oxfordjournals.org/content/14/suppl_1/i5.long Zelenetz et al. 2003]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
-''Third cycle intended to be followed by peripheral blood stem cell collection''
+''Third cycle intended to be followed by peripheral blood hematopoietic cell collection''
 ====Chemotherapy====
 *[[Ifosfamide (Ifex)]] 5,000 mg/m<sup>2</sup> IV continuous infusion over 24 hours on day 2, mixed together with [[Mesna (Mesnex)]]
@@ Line 3,048: / Line 2,706: @@
 ====Supportive medications====
 *[[Mesna (Mesnex)]] 5,000 mg/m<sup>2</sup> IV continuous infusion over 24 hours on day 2, mixed together with [[Ifosfamide (Ifex)]]
-*[[Filgrastim (Neupogen)]] 5 µg/kg SC once per day on days 5 to 12 (10 µg/kg with cycle 3, given until collection of peripheral blood stem cells)
+*[[Filgrastim (Neupogen)]] 5 µg/kg SC once per day on days 5 to 12 (10 µg/kg with cycle 3, given until collection of peripheral blood hematopoietic cells)
 ===References===
-# Moskowitz CH, Bertino JR, Glassman JR, Hedrick EE, Hunte S, Coady-Lyons N, Agus DB, Goy A, Jurcic J, Noy A, O'Brien J, Portlock CS, Straus DS, Childs B, Frank R, Yahalom J, Filippa D, Louie D, Nimer SD, Zelenetz AD. Ifosfamide, carboplatin, and etoposide: a highly effective cytoreduction and peripheral-blood progenitor-cell mobilization regimen for transplant-eligible patients with non-Hodgkin's lymphoma. J Clin Oncol. 1999 Dec;17(12):3776-85. [http://jco.ascopubs.org/content/17/12/3776.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/10577849 PubMed]
+# Moskowitz CH, Bertino JR, Glassman JR, Hedrick EE, Hunte S, Coady-Lyons N, Agus DB, Goy A, Jurcic J, Noy A, O'Brien J, Portlock CS, Straus DS, Childs B, Frank R, Yahalom J, Filippa D, Louie D, Nimer SD, Zelenetz AD. Ifosfamide, carboplatin, and etoposide: a highly effective cytoreduction and peripheral-blood progenitor-cell mobilization regimen for transplant-eligible patients with non-Hodgkin's lymphoma. J Clin Oncol. 1999 Dec;17(12):3776-85. [http://jco.ascopubs.org/content/17/12/3776.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10577849 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''' [http://www.ncbi.nlm.nih.gov/pubmed/12736224 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]
-# Hertzberg MS, Crombie C, Benson W, Taper J, Gottlieb D, Bradstock KF. Outpatient-based ifosfamide, carboplatin and etoposide (ICE) chemotherapy in transplant-eligible patients with non-Hodgkin's lymphoma and Hodgkin's disease. Ann Oncol. 2003;14 Suppl 1:i11-6. [http://annonc.oxfordjournals.org/content/14/suppl_1/i11.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/12736225 PubMed]
+# Hertzberg MS, Crombie C, Benson W, Taper J, Gottlieb D, Bradstock KF. Outpatient-based ifosfamide, carboplatin and etoposide (ICE) chemotherapy in transplant-eligible patients with non-Hodgkin's lymphoma and Hodgkin's disease. Ann Oncol. 2003;14 Suppl 1:i11-6. [http://annonc.oxfordjournals.org/content/14/suppl_1/i11.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12736225 PubMed]
 ==Lenalidomide (Revlimid) {{#subobject:f5ca0d|Regimen=1}}==
@@ Line 3,067: / Line 2,725: @@
 |-
 |[http://jco.ascopubs.org/content/26/30/4952.long Wiernik et al. 2008 (NHL-002)]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |[http://annonc.oxfordjournals.org/content/22/7/1622.long Witzig et al. 2011 (NHL-003)]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 3,089: / Line 2,737: @@
 ===References===
-# 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''' [http://www.ncbi.nlm.nih.gov/pubmed/18606983 PubMed]
+# 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]
-# 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''' [http://www.ncbi.nlm.nih.gov/pubmed/21228334 PubMed]
+# 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]
 ==Lenalidomide & Rituximab {{#subobject:d4c873|Regimen=1}}==
@@ Line 3,104: / Line 2,752: @@
 |-
 |[http://www.nature.com/leu/journal/v27/n9/full/leu201395a.html Wang et al. 2013]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 3,124: / Line 2,767: @@
 |-
 |[http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(11)00023-1/abstract Zinzani et al. 2011]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 3,141: / Line 2,779: @@
 ===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''' [http://www.ncbi.nlm.nih.gov/pubmed/21859554 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. [http://onlinelibrary.wiley.com/doi/10.1002/hon.2049/abstract link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/23620452 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. [http://onlinelibrary.wiley.com/doi/10.1002/hon.2049/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23620452 PubMed]
-# 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. [http://www.nature.com/leu/journal/v27/n9/full/leu201395a.html link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23545991 PubMed]
+# 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. [http://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 (Novantrone) {{#subobject:6e3e59|Regimen=1}}==
@@ Line 3,156: / Line 2,794: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://www.ncbi.nlm.nih.gov/pubmed/3282421 Bajetta et al. 1988]
+|[https://www.ncbi.nlm.nih.gov/pubmed/3282421 Bajetta et al. 1988]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 3,171: / Line 2,804: @@
 ===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''' [http://www.ncbi.nlm.nih.gov/pubmed/3282421 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]
-# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70212-7/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22652183 PubMed]
+# 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. [http://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 (Gazyva) {{#subobject:9d2627|Regimen=1}}==
@@ Line 3,186: / Line 2,819: @@
 |-
 |[http://jco.ascopubs.org/content/31/23/2912.long Morschhauser et al. 2013 (GAUGUIN)]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 3,210: / Line 2,838: @@
 ===References===
-# 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''' [http://www.ncbi.nlm.nih.gov/pubmed/23835718 PubMed]
+# 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]
 ==O-DHAP {{#subobject:49372b|Regimen=1}}==
@@ Line 3,225: / Line 2,853: @@
 |-
 |[http://bloodjournal.hematologylibrary.org/content/122/4/499.long Matasar et al. 2013]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 3,248: / Line 2,871: @@
 ===References===
 <!-- Presented at the 2011 American Society of Hematology Annual Meeting, San Diego, CA, December 10-13, 2011. -->
-# 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://bloodjournal.hematologylibrary.org/content/122/4/499.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23692856 PubMed]
+# 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://bloodjournal.hematologylibrary.org/content/122/4/499.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23692856 PubMed]
 ==O-ICE {{#subobject:f3f288|Regimen=1}}==
@@ Line 3,263: / Line 2,886: @@
 |-
 |[http://bloodjournal.hematologylibrary.org/content/122/4/499.long Matasar et al. 2013]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 3,288: / Line 2,906: @@
 ===References===
 <!-- Presented at the 2011 American Society of Hematology Annual Meeting, San Diego, CA, December 10-13, 2011. -->
-# 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://bloodjournal.hematologylibrary.org/content/122/4/499.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23692856 PubMed]
+# 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://bloodjournal.hematologylibrary.org/content/122/4/499.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23692856 PubMed]
 ==Ofatumumab (Arzerra) {{#subobject:5ba252|Regimen=1}}==
@@ Line 3,302: / Line 2,920: @@
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1111/bjh.12537/full Coiffier et al. 2013 (415 Study)]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 3,321: / Line 2,934: @@
 ===References===
-# Coiffier B, Radford J, Bosly A, Martinelli 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.12537/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24032456 PubMed]
+# Coiffier B, Radford J, Bosly A, Martinelli 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. [http://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]
 ==R-BL {{#subobject:fe578a|Regimen=1}}==
@@ Line 3,337: / Line 2,950: @@
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1111/bjh.14049/abstract Hitz et al. 2016 (SAKK 38/08)]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#eeee00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |61% (95% CI 45-76%)
 |-
@@ Line 3,354: / Line 2,962: @@
 ===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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.14049/abstract link to original article] '''contains protocol''' [http://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. [http://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 3,369: / Line 2,977: @@
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1111/bjh.13195/full Straus et al. 2014]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 3,389: / Line 2,992: @@
 ===References===
-# 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.13195/full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/25316653 PubMed]
+# 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. [http://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-DexaBEAM {{#subobject:81a0a4|Regimen=1}}==
@@ Line 3,404: / Line 3,007: @@
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1111/bjh.13234/full Kirschey et al. 2014]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 3,422: / Line 3,020: @@
 '''3- to 4-week cycle for 2 cycles'''
-''Patient proceed to undergo [[Diffuse_large_B-cell_lymphoma#Autologous_stem_cell_transplant|high dose therapy and autologous stem cell transplant]].''
+''Patient proceed to undergo [[Diffuse_large_B-cell_lymphoma#Autologous_hematopoietic_cell_transplant|high dose therapy and autologous hematopoietic cell transplant]].''
 ===References===
-# 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.13234/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/25546611 PubMed]
+# 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. [http://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-DHAP {{#subobject:a75946|Regimen=1}}==
@@ Line 3,440: / Line 3,038: @@
 |-
 |[http://informahealthcare.com/doi/full/10.1080/07357900600814490 Mey et al. 2006]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 3,471: / Line 3,064: @@
 '''3-week cycle up to 3 cycles (4 cycles, total)'''
-''Patients with complete or partial response were allowed to undergo [[Diffuse_large_B-cell_lymphoma#Autologous_stem_cell_transplant|autologous stem-cell transplant]].''
+''Patients with complete or partial response were allowed to undergo [[Diffuse_large_B-cell_lymphoma#Autologous_hematopoietic_cell_transplant|autologous stem-cell transplant]].''
 ===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. [http://informahealthcare.com/doi/full/10.1080/07357900600814490 link to original article] '''contains verified protocol''' [http://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. [http://informahealthcare.com/doi/full/10.1080/07357900600814490 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16982464 PubMed]
 ==R-EPOCH {{#subobject:ddfe7d|Regimen=1}}==
@@ Line 3,489: / Line 3,082: @@
 |-
 |[http://annonc.oxfordjournals.org/content/15/3/511.long Jermann et al. 2004]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 3,510: / Line 3,098: @@
 ===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''' [http://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-GDP {{#subobject:20e899|Regimen=1}}==
@@ Line 3,525: / Line 3,113: @@
 |-
 |[http://link.springer.com/article/10.1007%2Fs12032-012-0211-2 Hou et al. 2012]
-|<span
+|style="background-color:#eeee00"|Non-randomized
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Non-randomized</span>
 |-
 |}
@@ Line 3,542: / Line 3,125: @@
 ===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] [http://www.ncbi.nlm.nih.gov/pubmed/22476761 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]
 ==R-GemOx {{#subobject:bb9813|Regimen=1}}==
@@ Line 3,557: / Line 3,140: @@
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1111/j.1600-0609.2007.00996.x/full López et al. 2008]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 3,578: / Line 3,156: @@
 |-
 |[http://annonc.oxfordjournals.org/content/18/8/1363.long El Gnaoui et al. 2007]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 3,600: / Line 3,173: @@
 ===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''' [http://www.ncbi.nlm.nih.gov/pubmed/17496309 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]
-# 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. [http://onlinelibrary.wiley.com/doi/10.1111/j.1600-0609.2007.00996.x/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18005385 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. [http://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''' [http://www.ncbi.nlm.nih.gov/pubmed/23753028 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/pubmed/23753028 PubMed]
 ==R-ICE {{#subobject:9915f9|Regimen=1}}==
@@ Line 3,617: / Line 3,190: @@
 |-
 |[http://www.hematoline.com/CN/abstract/abstract1538.shtml Guo et al. 2014]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 3,639: / Line 3,207: @@
 |-
 |[http://annonc.oxfordjournals.org/content/14/suppl_1/i5.long Zelenetz et al. 2003]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |[http://bloodjournal.hematologylibrary.org/content/103/10/3684.long Kewalramani et al. 2004]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
-''Third cycle intended to be followed by peripheral blood stem cell collection''
+''Third cycle intended to be followed by peripheral blood hematopoietic cell collection''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 3,672: / Line 3,230: @@
 *[[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 µg/kg SC once per day on days 7 to 14 (10 µg/kg with cycle 3, given until collection of peripheral blood stem cells)
+*[[Filgrastim (Neupogen)]] 5 µg/kg SC once per day on days 7 to 14 (10 µg/kg with cycle 3, given until collection of peripheral blood hematopoietic cells)
 ===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''' [http://www.ncbi.nlm.nih.gov/pubmed/12736224 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://bloodjournal.hematologylibrary.org/content/103/10/3684.long link to original article] '''contains regimen''' [http://www.ncbi.nlm.nih.gov/pubmed/14739217 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://bloodjournal.hematologylibrary.org/content/103/10/3684.long link to original article] '''contains regimen''' [https://www.ncbi.nlm.nih.gov/pubmed/14739217 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://www.hematoline.com/CN/abstract/abstract1538.shtml link to original article] [http://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://www.hematoline.com/CN/abstract/abstract1538.shtml link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24759019 PubMed]
 ==RICER {{#subobject:28fda|Regimen=1}}==
@@ Line 3,692: / Line 3,250: @@
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1111/bjh.12846/full Feldman et al. 2014]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 3,715: / Line 3,268: @@
 '''14-day cycle for 2 cycles'''
-''Responders received a 3rd cycle with stem cell collection 10 to 14 days afterwards, followed by [[Diffuse_large_B-cell_lymphoma#Autologous_stem_cell_transplant|autologous stem cell transplant]].''
+''Responders received a 3rd cycle with hematopoietic cell collection 10 to 14 days afterwards, followed by [[Diffuse_large_B-cell_lymphoma#Autologous_hematopoietic_cell_transplant|autologous hematopoietic cell transplant]].''
 ===References===
-# 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.12846/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24661044 PubMed]
+# 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.12846/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24661044 PubMed]
 ==R-IFE {{#subobject:19b4ea|Regimen=1}}==
@@ Line 3,733: / Line 3,286: @@
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1111/bjh.13036/full Pardal et al. 2014]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 3,754: / Line 3,302: @@
 '''2 cycles (duration not specified)'''
-''Responders proceeded to undergo [[Diffuse_large_B-cell_lymphoma#Autologous_stem_cell_transplant|autologous stem cell transplant]].''
+''Responders proceeded to undergo [[Diffuse_large_B-cell_lymphoma#Autologous_hematopoietic_cell_transplant|autologous hematopoietic cell transplant]].''
 ===References===
-# 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.13036/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/25066542 PubMed]
+# 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. [http://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 3,772: / Line 3,320: @@
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1111/bjh.12379/full Gyan et al. 2013]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 3,796: / Line 3,339: @@
 '''28-day cycle for 3 cycles'''
-''Responders were recommended to undergo 3 additional cycles or [[Diffuse_large_B-cell_lymphoma#Autologous_stem_cell_transplant|autologous stem cell transplant]].''
+''Responders were recommended to undergo 3 additional cycles or [[Diffuse_large_B-cell_lymphoma#Autologous_hematopoietic_cell_transplant|autologous hematopoietic cell transplant]].''
 ===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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.12379/full link to original article] '''contains verified protocol''' [http://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. [http://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]
 ==Temsirolimus (Torisel) {{#subobject:4baa29|Regimen=1}}==
@@ Line 3,813: / Line 3,356: @@
 |-
 |[http://jco.ascopubs.org/content/28/31/4740.long Smith et al. 2010]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 3,827: / Line 3,365: @@
 ===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''' [http://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/pubmed/20837940 PubMed]
 ==TTR {{#subobject:934c01|Regimen=1}}==
@@ Line 3,842: / Line 3,380: @@
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1111/bjh.13014/full Westin et al. 2014]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 3,863: / Line 3,396: @@
 ===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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.13014/full link to original article] '''contains verified protocol''' [http://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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.13014/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25039868 PubMed]
 =Consolidation and/or maintenance after salvage therapy=
-==Autologous stem cell transplant {{#subobject:0341c3|Regimen=1}}==
+==Autologous hematopoietic cell transplant {{#subobject:0341c3|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
@@ Line 3,880: / Line 3,413: @@
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJM199512073332305 Philip et al. 1995 (PARMA)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Diffuse_large_B-cell_lymphoma#DHAP|DHAP x4]]
-|<span
+|style="background-color:#00cd00"|Seems to have superior OS
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Increased OS</span>
 |-
 |}
@@ Line 3,898: / Line 3,421: @@
 ''Treatment preceded by [[Diffuse_large_B-cell_lymphoma#DHAP|DHAP x 2]]. Radiation was also given to sites of bulky disease (>5cm); see paper for details.''
-*[[Transplant_conditioning_regimens#BEAC|BEAC]] followed by autologous stem cell transplant
+*[[Transplant_conditioning_regimens#BEAC|BEAC]] followed by autologous hematopoietic cell transplant
 ''Follow the link for details.''
@@ Line 3,908: / Line 3,431: @@
 |-
 |[http://jco.ascopubs.org/content/28/27/4184.long Gisselbrecht et al. 2010 (CORAL)]
-|<span
+|style="background-color:#eeee00"|Non-randomized
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Non-randomized</span>
-|-
-!colspan="4" align="center"|
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1111/bjh.13036/full Pardal et al. 2014]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 3,929: / Line 3,440: @@
 ''Treatment in CORAL preceded by [[Diffuse_large_B-cell_lymphoma#R-ICE|R-ICE x 3]] versus [[Diffuse_large_B-cell_lymphoma#R-DHAP|R-DHAP x 3]]. Treatment in Pardal et al. 2014 preceded by [[Diffuse_large_B-cell_lymphoma#R-MegaCHOP|R-MegaCHOP x3]] and [[Diffuse_large_B-cell_lymphoma#R-IFE|R-IFE x 2]].''
-*[[Transplant_conditioning_regimens#BEAM|BEAM]] followed by autologous stem cell transplant
+*[[Transplant_conditioning_regimens#BEAM|BEAM]] followed by autologous hematopoietic cell transplant
 ''Follow the link for details. In CORAL, treatment was followed by [[Diffuse_large_B-cell_lymphoma#Rituximab_.28Rituxan.29_2|maintenance rituximab]] versus [[Diffuse_large_B-cell_lymphoma#Observation_2|observation]].''
@@ Line 3,939: / Line 3,450: @@
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1111/bjh.12846/full Feldman et al. 2014]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 3,950: / Line 3,456: @@
 ''Treatment preceded by [[Diffuse_large_B-cell_lymphoma#RICER|RICER x 3]].''
-*[[Transplant_conditioning_regimens#BEAM|BEAM]] followed by autologous stem cell transplant
+*[[Transplant_conditioning_regimens#BEAM|BEAM]] followed by autologous hematopoietic cell transplant
 ''Follow the link for details. If patients were fully recovered within 90 days, they proceeded to [[Diffuse_large_B-cell_lymphoma#Lenalidomide_.28Revlimid.29_2|lenalidomide maintenance]].''
@@ Line 3,960: / Line 3,466: @@
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1111/bjh.13234/full Kirschey et al. 2014]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 3,971: / Line 3,472: @@
 ''Treatment preceded by [[Diffuse_large_B-cell_lymphoma#R-DexaBEAM|R-DexaBEAM x 2]].''
-*[[Transplant_conditioning_regimens#R-BEAM|R-BEAM]] or [[Transplant_conditioning_regimens#R-TBI.2FCy|R-TBI/Cy]] followed by autologous stem cell transplant
+*[[Transplant_conditioning_regimens#R-BEAM|R-BEAM]] or [[Transplant_conditioning_regimens#R-TBI.2FCy|R-TBI/Cy]] followed by autologous hematopoietic cell transplant
 ===References===
-# Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, et al. 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. [http://www.nejm.org/doi/full/10.1056/NEJM199512073332305 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/7477169 PubMed]
+# Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, et al. 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. [http://www.nejm.org/doi/full/10.1056/NEJM199512073332305 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7477169 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''' [http://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/pubmed/20660832 PubMed]
-# 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.12846/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24661044 PubMed]
+# 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.12846/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24661044 PubMed]
-# 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.13036/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/25066542 PubMed]
+# 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. [http://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]
 <!-- 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. -->
-# 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''' [http://www.ncbi.nlm.nih.gov/pubmed/25267740 PubMed]
+# 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]
-# 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.13234/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/25546611 PubMed]
+# 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. [http://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]
 ==Lenalidomide (Revlimid) {{#subobject:e4284f|Regimen=1}}==
@@ Line 3,996: / Line 3,497: @@
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1111/bjh.12846/full Feldman et al. 2014]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
-''Treatment preceded by [[Diffuse_large_B-cell_lymphoma#Autologous_stem_cell_transplant|BEAM autologous transplant]].''
+''Treatment preceded by [[Diffuse_large_B-cell_lymphoma#Autologous_hematopoietic_cell_transplant|BEAM autologous transplant]].''
 ====Chemotherapy====
 *[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
@@ Line 4,017: / Line 3,513: @@
 |-
 |[http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(11)00023-1/abstract Zinzani et al. 2011]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 4,033: / Line 3,524: @@
 ===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''' [http://www.ncbi.nlm.nih.gov/pubmed/21859554 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. [http://onlinelibrary.wiley.com/doi/10.1002/hon.2049/abstract link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/23620452 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. [http://onlinelibrary.wiley.com/doi/10.1002/hon.2049/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23620452 PubMed]
-# 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.12846/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24661044 PubMed]
+# 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.12846/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24661044 PubMed]
 ==Observation==
@@ Line 4,051: / Line 3,542: @@
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1111/bjh.12846/full Gisselbrecht et al. 2012 (CORAL)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Diffuse_large_B-cell_lymphoma#Rituximab_.28Rituxan.29_2|Rituximab]]
-|<span
+|style="background-color:#eeee00"|Seems not superior
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Seems not superior</span>
 |-
 |}
-''No further treatment after [[Diffuse_large_B-cell_lymphoma#Autologous_stem_cell_transplant|BEAM autologous stem cell transplant]].''
+''No further treatment after [[Diffuse_large_B-cell_lymphoma#Autologous_hematopoietic_cell_transplant|BEAM autologous hematopoietic cell transplant]].''
 ===References===
 <!-- Presented at the 45th Annual Meeting of the American Society of Clinical Oncology, June 4-6, 2011, Chicago, IL. -->
-# 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.12846/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23091101 PubMed]
+# 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.12846/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23091101 PubMed]
 ==Rituximab (Rituxan) {{#subobject:4a4553|Regimen=1}}==
@@ Line 4,087: / Line 3,568: @@
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1111/bjh.12846/full Gisselbrecht et al. 2012 (CORAL)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Diffuse_large_B-cell_lymphoma#Observation_2|Observation]]
-|<span
+|style="background-color:#eeee00"|Seems not superior
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Seems not superior</span>
 |-
 |}
-''Treatment preceded by [[Diffuse_large_B-cell_lymphoma#Autologous_stem_cell_transplant|BEAM autologous stem cell transplant]], and begins on day +28.''
+''Treatment preceded by [[Diffuse_large_B-cell_lymphoma#Autologous_hematopoietic_cell_transplant|BEAM autologous hematopoietic cell transplant]], and begins on day +28.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once every 8 weeks
@@ Line 4,111: / Line 3,582: @@
 ===References===
 <!-- Presented at the 45th Annual Meeting of the American Society of Clinical Oncology, June 4-6, 2011, Chicago, IL. -->
-# 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.12846/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23091101 PubMed]
+# 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.12846/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23091101 PubMed]
 =Response criteria=
 ==NCI Sponsored International Working Group Criteria (1999)==
-# Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-López A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999 Apr;17(4):1244. Review. Erratum in: J Clin Oncol 2000 Jun;18(11):2351. [http://jco.ascopubs.org/content/17/4/1244.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/10561185 PubMed]
+# Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-López A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999 Apr;17(4):1244. Review. Erratum in: J Clin Oncol 2000 Jun;18(11):2351. [http://jco.ascopubs.org/content/17/4/1244.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10561185 PubMed]
 ==Revised International Prognostic Index, R-IPI (2007)==
-# 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] [http://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]
 ==International Harmonization Project on Lymphoma revised criteria (2007)==
-# Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V; International Harmonization Project on Lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007 Feb 10;25(5):579-86. Epub 2007 Jan 22. [http://jco.ascopubs.org/content/25/5/579.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/17242396 PubMed]
+# Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V; International Harmonization Project on Lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007 Feb 10;25(5):579-86. Epub 2007 Jan 22. [http://jco.ascopubs.org/content/25/5/579.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17242396 PubMed]
 =Prognosis=
@@ Line 4,132: / Line 3,603: @@
 |}
 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. [http://www.nejm.org/doi/full/10.1056/NEJM199309303291402 link to original article] [http://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. [http://www.nejm.org/doi/full/10.1056/NEJM199309303291402 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8141877 PubMed]
 ==CNS-IPI (2016)==

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

Revision as of 02:37, 9 October 2016

Untreated, pre-phase

Vincristine & Prednisone

Regimen

Chemotherapy

References

Untreated, randomized data

ACVBP-R

Regimen

Chemotherapy

CNS prophylaxis

Supportive medications

References

CHOP

Regimen #1

Chemotherapy

Regimen #2

Chemotherapy

Supportive medications

Radiation therapy for initial bulky disease (NHL-B2)

Regimen #3, CHOP x 3 -> XRT

Chemotherapy

Radiotherapy

Regimen #4

Chemotherapy

Supportive medications

Regimen #5

Chemotherapy

Supportive medications

References

CHOP Intensified

Regimen #1

Chemotherapy

Supportive medications

Regimen #2

Chemotherapy

Supportive medications

Regimen #3

Chemotherapy

Radiation therapy for initial bulky disease

References

CHOP Modified

Regimen

Chemotherapy

References

CNOP; MCOP

Regimen

Chemotherapy

References

R-CHOEP-14

Regimen #1

Chemotherapy

Radiotherapy

Regimen #2, with CNS prophylaxis

R-CHOEP portion

Supportive medications

CNS Prophylaxis

HiDAC portion

HD-MTX portion

Supportive medications

Radiotherapy

References

R-CHOP

Regimen #1, prednisolone 40 mg/m2

Chemotherapy

CNS prophylaxis

Supportive medications

Regimen #2, prednisone 100 mg/m2

Chemotherapy

Regimen #3, prednisone 40 mg/m2

Chemotherapy

CNS prophylaxis

Supportive medications

Regimen #4, prednisone 100 mg, flat-dose vincristine

Chemotherapy

Supportive medications

Radiotherapy

Regimen #5, rituximab lead-in

Chemotherapy

Regimen #1, prednisolone 40 mg/m²

Regimen #2, prednisone 100 mg/m²

Regimen #3, prednisone 40 mg/m²