Autologous HSCT

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Unlike the other chemotherapy regimen pages, this one is not disease-specific. Rather, this is a gathering point for all autologous hematopoietic stem cell transplant (HSCT) conditioning regimens. Unless otherwise specified, the day of hematopoietic stem cell reinfusion is by convention day 0.

26 regimens on this page 54 variants on this page

High Dose Therapy Conditioning regimens

BCNU/TT

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BCNU/TT: BCNU (Carmustine), ThioTepa

Regimen #1

Study	Evidence
Illerhaus et al. 2006	Phase II

Chemotherapy

• Carmustine (BiCNU) 400 mg/m² IV once on day 50
• Thiotepa (Thioplex) 5 mg/kg (route not specified) once per day on days 51 & 52

Supportive medications

• Granulocyte colony-stimulating factor starting on day 61, continued until WBC greater than 1 x 10⁹/L for 3 days
• "Standard supportive measures were taken according to institutional guidelines."

Stem cells re-infused on day 56

Regimen #2

Study	Evidence
Illerhaus et al. 2008	Pilot, <20 pts

Chemotherapy

• Carmustine (BiCNU) 400 mg/m² IV once on day 1
• Thiotepa (Thioplex) 5 mg/kg (route not specified) BID on days 2 & 3

Stem cells re-infused on day 7

References

1. Illerhaus G, Marks R, Ihorst G, Guttenberger R, Ostertag C, Derigs G, Frickhofen N, Feuerhake F, Volk B, Finke J. High-dose chemotherapy with autologous stem-cell transplantation and hyperfractionated radiotherapy as first-line treatment of primary CNS lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3865-70. Epub 2006 Jul 24. link to original article contains verified protocol PubMed
2. Illerhaus G, Müller F, Feuerhake F, Schäfer AO, Ostertag C, Finke J. High-dose chemotherapy and autologous stem-cell transplantation without consolidating radiotherapy as first-line treatment for primary lymphoma of the central nervous system. Haematologica. 2008 Jan;93(1):147-8. link to original article contains verified protocol PubMed

BEAC

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

Regimen #1

Study	Evidence
Geisler et al. 2008 (MCL1/MCL2)	Phase II

Chemotherapy

• Carmustine (BiCNU) 300 mg/m² IV once on day 1
• Etoposide (Vepesid) 100 mg/m² IV BID on days 2 to 5
• Cytarabine (Cytosar) 400 mg/m² IV once per day on days 2 to 5
• Cyclophosphamide (Cytoxan) 1500 mg/m² IV once per day on days 2 to 5

Regimen #2

Study	Evidence	Comparator	Efficacy
Philip et al. 1995 (PARMA)	Phase III	DHAP x 4	Seems to have superior OS

Chemotherapy

• Carmustine (BiCNU) 300 mg/m² IV over 30 to 60 minutes once on day 1
• Etoposide (Vepesid) 100 mg/m² IV over 30 to 60 minutes twice per day on days 2 to 5
• Cytarabine (Cytosar) 100 mg/m² IV over 30 minutes twice per day on days 2 to 5
• Cyclophosphamide (Cytoxan) 35 mg/kg IV over 60 minutes once per day on days 2 to 5

Supportive medications

• Mesna (Mesnex) 8.3 mg/kg IV over 30 minutes every 4 hours on days 2 to 5 (optional)

Stem cells re-infused on day 7 (48 hours after last dose of etoposide)

Regimen #3

Study	Evidence
Philip et al. 1991 (Parma)	Phase II

Chemotherapy

• Carmustine (BiCNU) 300 mg/m² IV over 30 minutes once on day -13
• Etoposide (Vepesid) 100 mg/m² IV twice per day on days -12 to -7
• Cytarabine (Cytosar) 100 mg/m² IV twice per day on days -12 to -9
• Cyclophosphamide (Cytoxan) 35 mg/kg IV over 60 minutes once per day on days -12 to -9

Supportive medications

• Mesna (Mesnex) 50 mg/kg IV every day on days -12 to -9 (optional)

Stem cells re-infused on day 0

References

1. Philip T, Chauvin F, Armitage J, Bron D, Hagenbeek A, Biron P, Spitzer G, Velasquez W, Weisenburger DD, Fernandez-Ranada J, et al. Parma international protocol: pilot study of DHAP followed by involved-field radiotherapy and BEAC with autologous bone marrow transplantation. Blood. 1991 Apr 1;77(7):1587-92. link to original article contains verified protocol PubMed
2. 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 contains verified protocol PubMed
3. Retrospective: Jo JC, Kang BW, Jang G, Sym SJ, Lee SS, Koo JE, Kim JW, Kim S, Huh J, Suh C. BEAC or BEAM high-dose chemotherapy followed by autologous stem cell transplantation in non-Hodgkin's lymphoma patients: comparative analysis of efficacy and toxicity. Ann Hematol. 2008 Jan;87(1):43-8. Epub 2007 Aug 21. link to original article contains protocol PubMed
4. Geisler CH, Kolstad A, Laurell A, Andersen NS, Pedersen LB, Jerkeman M, Eriksson M, Nordström M, Kimby E, Boesen AM, Kuittinen O, Lauritzsen GF, Nilsson-Ehle H, Ralfkiaer E, Akerman M, Ehinger M, Sundström C, Langholm R, Delabie J, Karjalainen-Lindsberg ML, Brown P, Elonen E; Nordic Lymphoma Group. Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group. Blood. 2008 Oct 1;112(7):2687-93. Epub 2008 Jul 14. link to original article link to PMC article contains verified protocol PubMed

BEAM

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

Regimen #1, 300/200/200q12/140

Study	Evidence	Comparator	Efficacy
Shimoni et al. 2012	Randomized Phase II	Z-BEAM	Seems to have inferior OS
van Imhoff et al. 2016 (ORCHARRD)	Non-randomized portion of RCT

Chemotherapy

• Carmustine (BiCNU) 300 mg/m² IV once on day -6
• Etoposide (Vepesid) 200 mg/m² IV once per day on days -5 to -2
• Cytarabine (Cytosar) 200 mg/m² IV Q12H on days -5 to -2 (8 total doses)
• Melphalan (Alkeran) 140 mg/m² IV once on day -1

Supportive medications

• Variously described
• Filgrastim (Neupogen) 5 mcg/kg SC once per day starting on day +4 "until engraftment"
• Valacyclovir (Valtrex) (dose not specified) for one month
• Trimethoprim/Sulfamethoxazole (Bactrim DS) (dose/frequency not specified) for six months

Regimen #2, 300/100q12/100q12/140 with 24-hour rest

Study	Evidence
Alvarnas et al. 2016 (BMT CTN 0803/AMC 071)	Phase II

Chemotherapy

• Carmustine (BiCNU) 300 mg/m² IV once on day -6
• Etoposide (Vepesid) 100 mg/m² IV Q12H on days -5 to -2 (8 total doses)
• Cytarabine (Cytosar) 100 mg/m² IV Q12H on days -5 to -2 (8 total doses)
• Melphalan (Alkeran) 140 mg/m² IV once on day -1

Regimen #3, 300/200/200/140

Study	Evidence
Gisselbrecht et al. 2010 (CORAL)	Non-randomized

Chemotherapy

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

Regimen #4, 300/100q12/400/140

Study	Evidence
Geisler et al. 2008 (MCL1/MCL2)	Phase II

Paper did not specify which day peripheral blood stem cells were administered.

Chemotherapy

• Carmustine (BiCNU) 300 mg/m² IV once on day 1
• Etoposide (Vepesid) 100 mg/m² IV BID on days 2 to 5 (8 total doses)
• Cytarabine (Cytosar) 400 mg/m² IV once per day on days 2 to 5
• Melphalan (Alkeran) 140 mg/m² IV once on day 6

Regimen #5, 300/100q12/100q12/140 with 48-hour rest

Study	Evidence
Van't Veer et al. 2008 (HOVON 45)	Phase II

Chemotherapy

• Carmustine (BiCNU) 300 mg/m² IV once on day -7
• Etoposide (Vepesid) 100 mg/m² IV Q12H on days -6 to -3 (8 total doses)
• Cytarabine (Cytosar) 100 mg/m² IV Q12H on days -6 to -3 (8 total doses)
• Melphalan (Alkeran) 140 mg/m² IV once on day -2

Regimen #6, 300/100q12/200q12/140

Study	Evidence
Abrey et al. 2003	Phase II
Stewart et al. 2006	Phase II

Chemotherapy

• Carmustine (BiCNU) 300 mg/m² IV once on day -6
• Etoposide (Vepesid) 100 mg/m² IV Q12H on days -5 to -2 (8 total doses)
• Cytarabine (Cytosar) 200 mg/m² IV Q12H on days -5 to -2 (8 total doses)
• Melphalan (Alkeran) 140 mg/m² IV once on day -1

Supportive medications

• Patients less than 70 kg: Filgrastim (Neupogen) 300 mcg SC once per day starting on day +7 after stem cell transplant
• Patients greater than 70 kg (reference did not clarify which dosage to use for patients who are exactly 70 kg): Filgrastim (Neupogen) 480 mcg SC once per day starting on day +7 after stem cell transplant
• Trimethoprim/Sulfamethoxazole (Bactrim DS) (160/800 mg) PO BID on Monday and Thursdays, until 6 months after BEAM

While ANC less than 500/uL:

• Ciprofloxacin (Cipro) 500 mg PO BID
• Fluconazole (Diflucan) 100 mg PO once per day or mycostatin 500,000 units swish & swallow QID
• Acyclovir (Zovirax) 400 mg PO TID

Regimen #7, 300/200/100q12/140

Study	Evidence
Colombat et al. 2006	Phase II

Paper did not specify which day peripheral blood stem cells were administered.

Chemotherapy

• Carmustine (BiCNU) 300 mg/m² IV once on day 1
• Etoposide (Vepesid) 200 mg/m² IV once per day on days 2 to 5
• Cytarabine (Cytosar) 100 mg/m² IV Q12H on days 2 to 5 (8 total doses)
• Melphalan (Alkeran) 140 mg/m² IV once on day 6

Regimen #8, 300/150q12/200q12/140

Study	Evidence
Josting et al. 2005	Phase II

Paper did not specify which day peripheral blood stem cells were administered.

Chemotherapy

• Carmustine (BiCNU) 300 mg/m² IV once on day 1
• Etoposide (Vepesid) 150 mg/m² IV Q12H on days 2 to 5 (8 total doses)
• Cytarabine (Cytosar) 200 mg/m² IV Q12H on days 2 to 5 (8 total doses)
• Melphalan (Alkeran) 140 mg/m² IV once on day 1

Regimen #9, 300/200/400/140

Study	Evidence
Jo et al. 2008	Retrospective

Chemotherapy

• Carmustine (BiCNU) 300 mg/m² IV once on day -6
• Etoposide (Vepesid) 200 mg/m² IV once per day on days -5 to -2
• Cytarabine (Cytosar) 400 mg/m² IV once per day on days -5 to -2
• Melphalan (Alkeran) 140 mg/m² IV once on day -1

Supportive medications

• Filgrastim (Neupogen) 5 mcg/kg SC once per day starting on day +1, continued until there are 3 consecutive days with ANC at least 1000/uL
• Prophylaxis against opportunistic infections and management of febrile neutropenia per "active protocols"

Regimen #10, 300/200q12/200q12/140

Study	Evidence
Zinzani et al. 2003	Retrospective

Chemotherapy

• Carmustine (BiCNU) 300 mg/m² IV once on day -7
• Etoposide (Vepesid) 200 mg/m² IV BID on days -6 to -3 (8 total doses)
• Cytarabine (Cytosar) 200 mg/m² IV BID on days -6 to -3 (8 total doses)
• Melphalan (Alkeran) 140 mg/m² IV once on day -2

References

1. Retrospective: Zinzani PL, Tani M, Gabriele A, Gherlinzoni F, de Vivo A, Ricci P, Bandini G, Lemoli RM, Motta MR, Rizzi S, Giudice V, Zompatori M, Stefoni V, Alinari L, Musuraca G, Bassi S, Conte R, Pileri S, Tura S, Baccarani M. High-dose therapy with autologous transplantation for Hodgkin's disease: the Bologna experience. Haematologica. 2003 May;88(5):522-8. link to original article contains verified protocol PubMed
2. Abrey LE, Moskowitz CH, Mason WP, Crump M, Stewart D, Forsyth P, Paleologos N, Correa DD, Anderson ND, Caron D, Zelenetz A, Nimer SD, DeAngelis LM. Intensive methotrexate and cytarabine followed by high-dose chemotherapy with autologous stem-cell rescue in patients with newly diagnosed primary CNS lymphoma: an intent-to-treat analysis. J Clin Oncol. 2003 Nov 15;21(22):4151-6. link to original article contains verified protocol PubMed
3. Zinzani PL, Tani M, Gabriele A, Gherlinzoni F, De Vivo A, Ricci P, Bandini G, Lemoli RM, Motta MR, Rizzi S, Guidice V, Zompatori M, Stefoni V, Alinari L, Musuraca G, Marchi E, Bassi S, Conte R, Pileri S, Tura S, Baccarani M. High-dose therapy with autologous transplantation for aggressive non-Hodgkin's lymphoma: the Bologna experience. Leuk Lymphoma. 2004 Feb;45(2):321-6. PubMed
4. Josting A, Sieniawski M, Glossmann JP, Staak O, Nogova L, Peters N, Mapara M, Dörken B, Ko Y, Metzner B, Kisro J, Diehl V, Engert A. High-dose sequential chemotherapy followed by autologous stem cell transplantation in relapsed and refractory aggressive non-Hodgkin's lymphoma: results of a multicenter phase II study. Ann Oncol. 2005 Aug;16(8):1359-65. Epub 2005 Jun 6. link to original article contains protocol PubMed
5. Stewart DA, Bahlis N, Valentine K, Balogh A, Savoie L, Morris DG, Jones A, Brown C, Russell JA. Upfront double high-dose chemotherapy with DICEP followed by BEAM and autologous stem cell transplantation for poor-prognosis aggressive non-Hodgkin lymphoma. Blood. 2006 Jun 15;107(12):4623-7. Epub 2006 Feb 7. link to original article contains protocol PubMed content property of HemOnc.org
6. Colombat P, Lemevel A, Bertrand P, Delwail V, Rachieru P, Brion A, Berthou C, Bay JO, Delepine R, Desablens B, Camilleri-Broët S, Linassier C, Lamy T. High-dose chemotherapy with autologous stem cell transplantation as first-line therapy for primary CNS lymphoma in patients younger than 60 years: a multicenter phase II study of the GOELAMS group. Bone Marrow Transplant. 2006 Sep;38(6):417-20. link to original article contains verified protocol PubMed
7. Retrospective: Jo JC, Kang BW, Jang G, Sym SJ, Lee SS, Koo JE, Kim JW, Kim S, Huh J, Suh C. BEAC or BEAM high-dose chemotherapy followed by autologous stem cell transplantation in non-Hodgkin's lymphoma patients: comparative analysis of efficacy and toxicity. Ann Hematol. 2008 Jan;87(1):43-8. Epub 2007 Aug 21. link to original article contains protocol PubMed
8. Geisler CH, Kolstad A, Laurell A, Andersen NS, Pedersen LB, Jerkeman M, Eriksson M, Nordström M, Kimby E, Boesen AM, Kuittinen O, Lauritzsen GF, Nilsson-Ehle H, Ralfkiaer E, Akerman M, Ehinger M, Sundström C, Langholm R, Delabie J, Karjalainen-Lindsberg ML, Brown P, Elonen E; Nordic Lymphoma Group. Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group. Blood. 2008 Oct 1;112(7):2687-93. Epub 2008 Jul 14. link to original article link to PMC article contains verified protocol PubMed
9. Van't Veer MB, de Jong D, MacKenzie M, Kluin-Nelemans HC, van Oers MH, Zijlstra J, Hagenbeek A, van Putten WL. High-dose Ara-C and beam with autograft rescue in R-CHOP responsive mantle cell lymphoma patients. Br J Haematol. 2009 Feb;144(4):524-30. Epub 2008 Nov 26. link to original article contains verified protocol PubMed
10. Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Brière J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. Epub 2010 Jul 26. Erratum in: J Clin Oncol. 2012 May 20;30(15):1896. link to original article contains verified protocol link to PMC article PubMed
11. Shimoni A, Avivi I, Rowe JM, Yeshurun M, Levi I, Or R, Patachenko P, Avigdor A, Zwas T, Nagler A. A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma. Cancer. 2012 Oct 1;118(19):4706-14. Epub 2012 Jan 17. link to original article contains verified protocol PubMed
12. 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
13. Alvarnas JC, Le Rademacher J, Wang Y, Little RF, Akpek G, Ayala E, Devine S, Baiocchi R, Lozanski G, Kaplan L, Noy A, Popat U, Hsu J, Morris LE Jr, Thompson J, Horowitz MM, Mendizabal A, Levine A, Krishnan A, Forman SJ, Navarro WH, Ambinder R. Autologous hematopoietic cell transplantation for HIV-related lymphoma: results of the BMT CTN 0803/AMC 071 trial. Blood. 2016 Aug 25;128(8):1050-8. Epub 2016 Jun 13. link to original article contains verified protocol link to PMC article PubMed
14. van Imhoff GW, McMillan A, Matasar MJ, Radford J, Ardeshna KM, Kuliczkowski K, Kim W, Hong X, Goerloev JS, Davies A, Barrigón MD, Ogura M, Leppä S, Fennessy M, Liao Q, van der Holt B, Lisby S, Hagenbeek A. Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy in Relapsed or Refractory Diffuse Large B-Cell Lymphoma: The ORCHARRD Study. J Clin Oncol. 2017 Feb 10;35(5):544-51. Epub 2016 Dec 28. link to original article link to data supplement verified protocol in supplement PubMed

BeEAM

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

Regimen

Study	Evidence
Visani et al. 2011	Phase I/II

Chemotherapy

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

Stem cells re-infused on day 0

References

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

Bor-HDM

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Bor-HDM: Bortezomib, High Dose Melphalan

Regimen

Study	Evidence
Roussel et al. 2009	Phase II

Chemotherapy

• Bortezomib (Velcade) 1 mg/m² IV once per day on days -6, -3, 1, 4
• Melphalan (Alkeran) 200 mg/m² IV once on day -2

Supportive medications

• "All patients received standard supportive care measures"

Stem cells re-infused on day 0

References

1. Roussel M, Moreau P, Huynh A, Mary JY, Danho C, Caillot D, Hulin C, Fruchart C, Marit G, Pégourié B, Lenain P, Araujo C, Kolb B, Randriamalala E, Royer B, Stoppa AM, Dib M, Dorvaux V, Garderet L, Mathiot C, Avet-Loiseau H, Harousseau JL, Attal M; Intergroupe Francophone du Myélome (IFM). Bortezomib and high-dose melphalan as conditioning regimen before autologous stem cell transplantation in patients with de novo multiple myeloma: a phase 2 study of the Intergroupe Francophone du Myelome (IFM). Blood. 2010 Jan 7;115(1):32-7. Epub 2009 Nov 2. link to original article contains verified protocol PubMed

Busulfan & Melphalan

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Regimen #1

Study	Evidence
Yanada et al. 2013	Phase II

This regimen was evaluated in the setting of relapsed acute promyelocytic leukemia.

Chemotherapy

• Busulfan (Myleran) 1 mg/kg PO q6h on days -6 to -4
• Melphalan (Alkeran) 70 mg/m² IV bolus once per day on days -3 & -2

Regimen #2

Study	Evidence
Strauss et al. 2003	Phase II

This regimen was evaluated in the setting of metastatic Ewing's sarcoma. Note that melphalan is reported as given on day 2 (not day -2) in the original reference but this is surely an error.

Chemotherapy

• Busulfan (Myleran) 150 mg/m² IV once per day on days -6 to -3
• Melphalan (Alkeran) 140 mg/m² IV once on day -2

References

1. Atra A, Whelan JS, Calvagna V, Shankar AG, Ashley S, Shepherd V, Souhami RL, Pinkerton CR. High-dose busulphan/melphalan with autologous stem cell rescue in Ewing's sarcoma. Bone Marrow Transplant. 1997 Nov;20(10):843-6. link to original article PubMed
2. Strauss SJ, McTiernan A, Driver D, Hall-Craggs M, Sandison A, Cassoni AM, Kilby A, Michelagnoli M, Pringle J, Cobb J, Briggs T, Cannon S, Witt J, Whelan JS. Single center experience of a new intensive induction therapy for ewing's family of tumors: feasibility, toxicity, and stem cell mobilization properties. J Clin Oncol. 2003 Aug 1;21(15):2974-81. link to original article contains verified protocol PubMed
3. Yanada M, Tsuzuki M, Fujita H, Fujimaki K, Fujisawa S, Sunami K, Taniwaki M, Ohwada A, Tsuboi K, Maeda A, Takeshita A, Ohtake S, Miyazaki Y, Atsuta Y, Kobayashi Y, Naoe T, Emi N; Japan Adult Leukemia Study Group. Phase 2 study of arsenic trioxide followed by autologous hematopoietic cell transplantation for relapsed acute promyelocytic leukemia. Blood. 2013 Apr 18;121(16):3095-102. Epub 2013 Feb 14. link to original article contains verified protocol PubMed

Bu/Cy

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Regimen

Study	Evidence	Comparator	Efficacy
Vellenga et al. 2011 (HOVON-SAKK AML-29/AML-42)	Phase III	Etoposide & Mitoxantrone	Might have superior RFS

Treatment preceded by 7+3i, then amsacrine & cytarabine.

Chemotherapy

• Busulfan (Myleran) 4 mg/kg PO (frequency not specified) on days -7 to -4
• Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 & -2

References

1. Vellenga E, van Putten W, Ossenkoppele GJ, Verdonck LF, Theobald M, Cornelissen JJ, Huijgens PC, Maertens J, Gratwohl A, Schaafsma R, Schanz U, Graux C, Schouten HC, Ferrant A, Bargetzi M, Fey MF, Löwenberg B; Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON).; Swiss Group for Clinical Cancer Research Collaborative Group (SAKK). Autologous peripheral blood stem cell transplantation for acute myeloid leukemia. Blood. 2011 Dec 1;118(23):6037-42. Epub 2011 Sep 27. link to original article contains verified protocol PubMed

Bu/TT

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Bu/TT: Busulfan, ThioTepa

Regimen

Study	Evidence
Montemurro et al. 2007 (OSHO-53)	Phase II

Chemotherapy

• Busulfan (Myleran) 4 mg/kg PO four times per day on days −8 to −5
• Thiotepa (Thioplex) 5 mg/kg IV once per day on days -4 & -3

References

1. Montemurro M, Kiefer T, Schüler F, Al-Ali HK, Wolf HH, Herbst R, Haas A, Helke K, Theilig A, Lotze C, Hirt C, Niederwieser D, Schwenke M, Krüger WH, Dölken G. Primary central nervous system lymphoma treated with high-dose methotrexate, high-dose busulfan/thiotepa, autologous stem-cell transplantation and response-adapted whole-brain radiotherapy: results of the multicenter Ostdeutsche Studiengruppe Hamato-Onkologie OSHO-53 phase II study. Ann Oncol. 2007 Apr;18(4):665-71. Epub 2006 Dec 21. link to original article contains verified protocol PubMed

CBV

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

Regimen #1

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

Chemotherapy

• Carmustine (BiCNU) 300 mg/m² IV once on day -6
• Etoposide (Vepesid) 60 mg/kg (IBW) IV once on day -4
• Cyclophosphamide (Cytoxan) 100 mg/kg (IBW) IV once on day -2

Regimen #2

Study	Evidence
Stiff et al. 1998	Phase II
Damon et al. 2009 (CALGB 59909)	Phase II

Chemotherapy

• Carmustine (BiCNU) 15 mg/kg (maximum dose of 550 mg/m²) IV over 1 hour once on day -6
• Etoposide (Vepesid) 60 mg/kg IV over 4 hours once on day -4
• Cyclophosphamide (Cytoxan) 100 mg/kg IV over 2 hours once on day -2

Supportive medications

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

Regimen #3, "CVB"

Study	Evidence
Zinzani et al. 2003	Retrospective

Chemotherapy

• Cyclophosphamide (Cytoxan) 1500 mg/m² IV once per day on days -6 to -3
• Etoposide (Vepesid) 250 mg/m² IV once per day on days -6 to -4
• Carmustine (BiCNU) 300 mg/m² IV once on day -6

References

1. Reece DE, Connors JM, Spinelli JJ, Barnett MJ, Fairey RN, Klingemann HG, Nantel SH, O'Reilly S, Shepherd JD, Sutherland HJ, et al. Intensive therapy with cyclophosphamide, carmustine, etoposide +/- cisplatin, and autologous bone marrow transplantation for Hodgkin's disease in first relapse after combination chemotherapy. Blood. 1994 Mar 1;83(5):1193-9. link to original article PubMed
2. Stiff PJ, Dahlberg S, Forman SJ, McCall AR, Horning SJ, Nademanee AP, Blume KG, LeBlanc M, Fisher RI. Autologous bone marrow transplantation for patients with relapsed or refractory diffuse aggressive non-Hodgkin's lymphoma: value of augmented preparative regimens--a Southwest Oncology Group trial. J Clin Oncol. 1998 Jan;16(1):48-55. link to original article contains verified protocol PubMed
3. Retrospective: Zinzani PL, Tani M, Gabriele A, Gherlinzoni F, de Vivo A, Ricci P, Bandini G, Lemoli RM, Motta MR, Rizzi S, Giudice V, Zompatori M, Stefoni V, Alinari L, Musuraca G, Bassi S, Conte R, Pileri S, Tura S, Baccarani M. High-dose therapy with autologous transplantation for Hodgkin's disease: the Bologna experience. Haematologica. 2003 May;88(5):522-8. link to original article contains verified protocol PubMed
4. Damon LE, Johnson JL, Niedzwiecki D, Cheson BD, Hurd DD, Bartlett NL, Lacasce AS, Blum KA, Byrd JC, Kelly M, Stock W, Linker CA, Canellos GP. Immunochemotherapy and autologous stem-cell transplantation for untreated patients with mantle-cell lymphoma: CALGB 59909. J Clin Oncol. 2009 Dec 20;27(36):6101-8. Epub 2009 Nov 16. link to original article contains protocol link to PMC article PubMed
5. Stiff PJ, Unger JM, Cook JR, Constine LS, Couban S, Stewart DA, Shea TC, Porcu P, Winter JN, Kahl BS, Miller TP, Tubbs RR, Marcellus D, Friedberg JW, Barton KP, Mills GM, LeBlanc M, Rimsza LM, Forman SJ, Fisher RI. Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. N Engl J Med. 2013 Oct 31;369(18):1681-90. link to original article contains verified protocol link to PMC article PubMed

CTCb

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CTCb: Cyclophosphamide, Thiotepa, Carboplatin

Regimen

Study	Evidence	Comparator	Efficacy
Eder et al. 1990	Phase I/II
Stadtmauer et al. 2000 (Philadelphia Bone Marrow Transplant Group)	Phase III	CMF	Seems not superior

No longer used, but of historical interest.

Chemotherapy

• Cyclophosphamide (Cytoxan)
• Thiotepa (Thioplex)
• Carboplatin (Paraplatin)

References

1. Eder JP, Elias A, Shea TC, Schryber SM, Teicher BA, Hunt M, Burke J, Siegel R, Schnipper LE, Frei E 3rd, Antman K. A phase I-II study of cyclophosphamide, thiotepa, and carboplatin with autologous bone marrow transplantation in solid tumor patients. J Clin Oncol. 1990 Jul;8(7):1239-45. link to original article PubMed
2. Stadtmauer EA, O'Neill A, Goldstein LJ, Crilley PA, Mangan KF, Ingle JN, Brodsky I, Martino S, Lazarus HM, Erban JK, Sickles C, Glick JH. Conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer. Philadelphia Bone Marrow Transplant Group. N Engl J Med. 2000 Apr 13;342(15):1069-76. link to original article PubMed

Cyclophosphamide, Etoposide, TBI

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Regimen

Study	Evidence
Stiff et al. 1998	Phase II

Chemoradiotherapy

• Cyclophosphamide (Cytoxan) 100 mg/kg IV over 1 to 2 hours once on day -2
• Etoposide (Vepesid) 60 mg/kg IV over 4 hours once on day -4
• Total body irradiation (TBI) with 150 cGy fractions given twice per day (fractions are at least 5 hours apart) x 8 fractions (total dose: 1200 cGy) over 4 days on days -8 to -5, with lung shielding for the final 600 Gy
  • Note: Table 1 of Stiff et al. 1998 lists the dosage of each fraction as being 120 cGy, in contrast to the body text under "treatment regimen" saying each fraction is 150 cGy. It is believed that the 150 cGy dose is correct since 8 fractions of this results in the correct total dose of 1200 cGy.

Supportive medications

• Diphenhydramine (Benadryl) 25 mg (route not specified) once 2 hours before Etoposide (Vepesid) to prevent allergic reaction
• Hydrocortisone (Cortef) 100 mg (route not specified) once 2 hours before Etoposide (Vepesid) to prevent allergic reaction
• "Continuous bladder irrigation and vigorous hydration were used" to protect against hemorrhagic cystitis

References

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

Cyclophosphamide & TBI

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TBI: Total Body Irradiation

Regimen

Study	Evidence
Dreyling et al. 2004	Phase III

Chemoradiotherapy

• Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 & -2
• TBI 1200 cGy in fractions on days –6 to –4 (pulmonary dosage was limited to 800 cGy)

References

1. Dreyling M, Lenz G, Hoster E, Van Hoof A, Gisselbrecht C, Schmits R, Metzner B, Truemper L, Reiser M, Steinhauer H, Boiron JM, Boogaerts MA, Aldaoud A, Silingardi V, Kluin-Nelemans HC, Hasford J, Parwaresch R, Unterhalt M, Hiddemann W. Early consolidation by myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission significantly prolongs progression-free survival in mantle-cell lymphoma: results of a prospective randomized trial of the European MCL Network. Blood. 2005 Apr 1;105(7):2677-84. Epub 2004 Dec 9. link to original article PubMed

Etoposide & TBI

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TBI: Total Body Irradiation

Regimen

Study	Evidence	Comparator	Efficacy
Rowe et al. 2005 (MRC UKALL XII/ECOG E2993)	Phase III	International ALL Trial consolidation and maintenance	Seems to have inferior OS

Note: this is the same preparative regimen used for allogeneic transplant for certain patients; see reference for details. This regimen was evaluated in the treatment of acute lymphoblastic leukemia in CR1.

Chemoradiotherapy

• Etoposide (Vepesid) 60 mg/kg IV once on day -3
• TBI 220 cGy twice per day in 6 fractions on days –6 to –4 (total dose: 1320 cGy)

References

1. Rowe JM, Buck G, Burnett AK, Chopra R, Wiernik PH, Richards SM, Lazarus HM, Franklin IM, Litzow MR, Ciobanu N, Prentice HG, Durrant J, Tallman MS, Goldstone AH; ECOG; MRC/NCRI Adult Leukemia Working Party. Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood. 2005 Dec 1;106(12):3760-7. Epub 2005 Aug 16. link to original article contains verified protocol PubMed
   1. Update: Goldstone AH, Richards SM, Lazarus HM, Tallman MS, Buck G, Fielding AK, Burnett AK, Chopra R, Wiernik PH, Foroni L, Paietta E, Litzow MR, Marks DI, Durrant J, McMillan A, Franklin IM, Luger S, Ciobanu N, Rowe JM. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood. 2008 Feb 15;111(4):1827-33. Epub 2007 Nov 29. link to original article PubMed
   2. Update: Fielding AK, Rowe JM, Richards SM, Buck G, Moorman AV, Durrant IJ, Marks DI, McMillan AK, Litzow MR, Lazarus HM, Foroni L, Dewald G, Franklin IM, Luger SM, Paietta E, Wiernik PH, Tallman MS, Goldstone AH. Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era: results from the International ALL Trial MRC UKALLXII/ECOG2993. Blood. 2009 May 7;113(19):4489-96. Epub 2009 Feb 24. link to original article link to PMC article PubMed
   3. Update: Fielding AK, Rowe JM, Buck G, Foroni L, Gerrard G, Litzow MR, Lazarus H, Luger SM, Marks DI, McMillan AK, Moorman AV, Patel B, Paietta E, Tallman MS, Goldstone AH. UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. Blood. 2014 Feb 6;123(6):843-50. Epub 2013 Nov 25. link to original article contains verified protocol link to PMC article PubMed

LEED

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

Regimen

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

Note: this protocol does not appear to be commonly used outside of Japan.

Chemotherapy

• Melphalan (Alkeran) 130 mg/m² IV once on day -1
• Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -4 & -3
• Etoposide (Vepesid) 500 mg/m² IV once per day on days -4 to -2
• Dexamethasone (Decadron) 40 mg IV once per day on days -4 to -1

References

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

Melphalan & TBI

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TBI: Total Body Irradiation

Regimen

Study	Evidence
Gressin et al. 2010 (LM1996/LM2001)	Phase II

Chemoradiotherapy

• Melphalan (Alkeran) 140 mg/m² IV once (day not specified)
• TBI: 800 cGy in 4 fractions (days not specified)

References

1. Gressin R, Caulet-Maugendre S, Deconinck E, Tournilhac O, Gyan E, Moles MP, El Yamani A, Cornillon J, Rossi JF, Le Gouill S, Lepeu G, Damaj G, Celigny PS, Maisonneuve H, Corront B, Vilque JP, Casassus P, Lamy T, Colonna M, Colombat P; French GOELAMS Group. Evaluation of the (R)VAD+C regimen for the treatment of newly diagnosed mantle cell lymphoma. Combined results of two prospective phase II trials from the French GOELAMS group. Haematologica. 2010 Aug;95(8):1350-7. Epub 2010 Mar 10. link to original article link to PMC article contains partial protocol PubMed

Melphalan monotherapy

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Regimen - immunoglobulin light-chain (AL) amyloidosis

Study	Evidence
Skinner et al. 2004	Phase II

Eligibility criteria: Biopsy-proven amyloid disease and at least 1 major organ involved, evidence of plasma cell dyscrasia, no heart failure or arrhythmia that cannot be medically managed, cardiac ejection fraction at least 40%, no pleural effusions, supine systolic blood pressure at least 90 mmHg, O2 saturation at least 95% on room air, lung diffusing capacity at least 50% predicted, SWOG performance status less than or equal to 2 unless due to neuropathy.

Chemotherapy

• Melphalan (Alkeran) as follows:
  • Patients who fulfilled all of these criteria--younger than 65 years old, cardiac ejection fraction at least 45%, and at least 2.5 x 10⁶ CD34+ cells/kg collected: 200 mg/m² total dose IV divided over two consecutive days
• Patients with at least one of these criteria-->65 years old, cardiac ejection fraction 40 to 44%, or with 2 to 2.5 x 10⁶ CD34+ cells/kg collected: 140 mg/m² total dose IV divided over two consecutive days

Autologous stem cell infusion occurs 24 to 72 hours after the last dose of melphalan

References

1. Barlogie B, Hall R, Zander A, Dicke K, Alexanian R. High-dose melphalan with autologous bone marrow transplantation for multiple myeloma. Blood. 1986 May;67(5):1298-301. link to original article PubMed
2. Skinner M, Sanchorawala V, Seldin DC, Dember LM, Falk RH, Berk JL, Anderson JJ, O'Hara C, Finn KT, Libbey CA, Wiesman J, Quillen K, Swan N, Wright DG. High-dose melphalan and autologous stem-cell transplantation in patients with AL amyloidosis: an 8-year study. Ann Intern Med. 2004 Jan 20;140(2):85-93. link to original article contains verified protocol PubMed
3. Royer B, Minvielle S, Diouf M, Roussel M, Karlin L, Hulin C, Arnulf B, Macro M, Cailleres S, Brion A, Brechignac S, Belhadj K, Chretien ML, Wetterwald M, Chaleteix C, Tiab M, Leleu X, Frenzel L, Garderet L, Choquet S, Fuzibet JG, Dauriac C, Forneker LM, Benboubker L, Facon T, Moreau P, Avet-Loiseau H, Marolleau JP. Bortezomib, Doxorubicin, Cyclophosphamide, Dexamethasone Induction Followed by Stem Cell Transplantation for Primary Plasma Cell Leukemia: A Prospective Phase II Study of the Intergroupe Francophone du Myélome. J Clin Oncol. 2016 Jun 20;34(18):2125-32. Epub 2016 Apr 25. link to original article contains protocol PubMed

R-BEAM

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

Regimen

Study	Evidence
Kirschey et al. 2014	Phase II

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

Chemotherapy

• Rituximab (Rituxan) 375 mg/m² IV once per day on days -8 & -2
• Carmustine (BiCNU) 300 mg/m² IV once on day -7
• Etoposide (Vepesid) 200 mg/m² IV BID on days -6 to -3
• Cytarabine (Cytosar) 400 mg/m² IV BID on days -6 to -3
• Melphalan (Alkeran) 140 mg/m² IV once on day -2

Patients in the Lyma trial were then randomized to rituximab maintenance versus observation.

References

1. 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
2. Abstract: Steven Le Gouill, MD, PhD, Catherine Thieblemont, MD, PhD, Lucie Oberic, Krimo Bouabdallah, MD, Emmanuel Gyan, MD, PhD, Gandhi Damaj, MD, Vincent Ribrag, MD, Serge Bologna, MD, Remy Gressin, MD, Olivier Casasnovas, MD, Corinne Haioun, MD, PhD, Philippe Solal-Celigny, MD, Herve Maisonneuve, MD, Eric Van Den Neste, MD, PhD, Anne Moreau, MD, Marie C Bene, Gilles Salles, MD PhD, Hervé Tilly, MD, PhD, Thierry Lamy, MD, PhD and Olivier Hermine, MD, PhD. Rituximab Maintenance Versus Wait and Watch after Four Courses of R-DHAP Followed By Autologous Stem Cell transplantation in Previously Untreated Young Patients with Mantle Cell Lymphoma: First Interim Analysis of the Phase III Prospective Lyma Trial, a Lysa Study. ASH Annual Meeting 2014, Abstract 146 link to abstract
3. Srour SA, Li S, Popat UR, Qazilbash MH, Lozano-Cerrada S, Maadani F, Alousi A,vKebriaei P, Anderlini P, Nieto Y, Jones R, Shpall E, Champlin RE, Hosing C. A randomized phase II study of standard-dose versus high-dose rituximab with BEAM in autologous stem cell transplantation for relapsed aggressive B-cell non-hodgkin lymphomas: long term results. Br J Haematol. 2017 Aug;178(4):561-570. Epub 2017 May 9. link to orignal article PubMed

R-TBI/Cy

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

Regimen

Study	Evidence
Kirschey et al. 2014	Phase II

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

Chemoradiotherapy

• Rituximab (Rituxan) 375 mg/m² IV once per day on days -8 & -2
• Total body irradiation (TBI) with a total dose of 12 Gy over 3 days (days -6 to -4) in fractions
• Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 & -2

References

1. 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

TAM6

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TAM: Total-body irradiation, Ara-C (Cytarabine), Melphalan

Regimen

Study	Evidence
Delarue et al. 2012	Phase II

Chemoradiotherapy

• Total body irradiation (TBI) with a total dose of 10 Gy over 3 days using twice per day fractions
• Cytarabine (Cytosar) 1500 mg/m² IV Q12H x 2 days (total of 4 total doses)
• Melphalan (Alkeran) 140 mg/m² IV

Supportive medications

"Antimicrobial prophylaxis and use of G-CSF or erythropoietin were permitted according to physician decision."

References

1. Delarue R, Haioun C, Ribrag V, Brice P, Delmer A, Tilly H, Salles G, Van Hoof A, Casasnovas O, Brousse N, Lefrere F, Hermine O; for the Groupe d'Etude des Lymphomes de l'Adulte (GELA). CHOP and DHAP plus rituximab followed by autologous stem cell transplantation in mantle cell lymphoma: a phase 2 study from the Groupe d'Etude des Lymphomes de l'Adulte. Blood. 2013 Jan 3;121(1):48-53. Epub 2012 Jun 20. link to original article contains verified protocol PubMed

TBC

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TBC: Thiotepa, Busulfan, , Cyclophosphamide
Bu/TT/Cy: Busulfan, ThioTepa, Cyclophosphamide

Regimen

Study	Evidence
Omuro et al. 2015	Phase II

Primary indication: primary CNS lymphoma (PCNSL)

Chemotherapy

• Thiotepa (Thioplex) 250 mg/m² IV once per day on days −9, −8, and −7
• Busulfan (Myleran) 3.2 mg/kg IV once per day on days −6, −5, and −4
• Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days −3 and −2

References

1. Omuro A, Correa DD, DeAngelis LM, Moskowitz CH, Matasar MJ, Kaley TJ, Gavrilovic IT, Nolan C, Pentsova E, Grommes CC, Panageas KS, Baser RE, Faivre G, Abrey LE, Sauter CS. R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma. Blood. 2015 Feb 26;125(9):1403-10. Epub 2015 Jan 7. link to original article contains verified protocol link to PMC article PubMed
2. Retrospective: DeFilipp Z, Li S, El-Jawahri A, Armand P, Nayak L, Wang N, Batchelor TT, Chen YB. High-dose chemotherapy with thiotepa, busulfan, and cyclophosphamide and autologous stem cell transplantation for patients with primary central nervous system lymphoma in first complete remission. Cancer. 2017 Aug 15;123(16):3073-3079. Epub 2017 Apr 3. link to original article PubMed

TBI

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TBI: Total Body Irradiation

Regimen

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

Radiotherapy

• TBI in 1.5-Gy fractions twice per day on days −8 through −5 (total dose: 12 Gy)

References

1. Stiff PJ, Unger JM, Cook JR, Constine LS, Couban S, Stewart DA, Shea TC, Porcu P, Winter JN, Kahl BS, Miller TP, Tubbs RR, Marcellus D, Friedberg JW, Barton KP, Mills GM, LeBlanc M, Rimsza LM, Forman SJ, Fisher RI. Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. N Engl J Med. 2013 Oct 31;369(18):1681-90. link to original article contains verified protocol link to PMC article PubMed

V-BEAM

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

Regimen

Study	Evidence
William et al. 2014	Phase II

Full details not available in abstract; to be added later.

Chemotherapy

• Bortezomib (Velcade) on days -11, -8, -5, -2
• Carmustine (BiCNU)
• Etoposide (Vepesid)
• Cytarabine (Cytosar)
• Melphalan (Alkeran)

References

1. William BM, Allen MS, Loberiza FR Jr, Bociek RG, Bierman PJ, Armitage JO, Vose JM. Phase I/II study of bortezomib-BEAM and autologous hematopoietic stem cell transplantation for relapsed indolent non-Hodgkin lymphoma, transformed, or mantle cell lymphoma. Biol Blood Marrow Transplant. 2014 Apr;20(4):536-42. Epub 2014 Jan 14. link to original article PubMed

Z-BEAM

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

Regimen #1

Study	Evidence	Comparator	Efficacy
Shimoni et al. 2012	Randomized Phase II	BEAM	Seems to have superior OS
Briones et al. 2013	Phase II

Patients in Shimoni et al. 2012 had primary induction failure or were chemosensitive to salvage therapy. Patients in Briones et al. 2013 had primary induction failure or were refractory to salvage therapy.

Chemoradioimmunotherapy

• Rituximab (Rituxan) 250 mg/m² IV once on day -14
• Ibritumomab tiuxetan & Yttrium-90 (Zevalin) 0.4 mCi/kg (maximum dose of 32 mCi) IV once on day -14, given after Rituximab (Rituxan)
• Carmustine (BiCNU) 300 mg/m² IV once on day -6
• Etoposide (Vepesid) 200 mg/m² IV once per day on days -5 to -2
• Cytarabine (Cytosar) 200 mg/m² IV Q12H on days -5 to -2
• Melphalan (Alkeran) 140 mg/m² IV once on day -1

Supportive medications

• Filgrastim (Neupogen) 5 mcg/kg SC once per day starting on day +4 (Shimoni et al. 2012) or day +7 (Briones et al. 2013) until engraftment
• Valacyclovir (Valtrex) (dose not specified) for one month (Shimoni et al. 2012)
• Acyclovir (Zovirax) (dose not specified) for one month (Briones et al. 2013)
• Trimethoprim/Sulfamethoxazole (Bactrim DS) (dose/frequency not specified) for six months (3 months in Briones et al. 2013)

Regimen #2

Study	Evidence
Fruchart et al. 2014	Phase II

This regimen is intended for upfront consolidation. Patients achieved at least a PR to R-ACVBP or R-CHOP.

Chemoradioimmunotherapy

• Rituximab (Rituxan) 250 mg/m² IV once per day on days -21 & -14
• Ibritumomab tiuxetan & Yttrium-90 (Zevalin) 0.4 mCi/kg (maximum dose of 32 mCi) IV once on day -14, given after Rituximab (Rituxan)
  • Dose reduced to 0.3 mCi/kg if platelet count was greater than 100 x 10⁹/L and less than 150 x 10⁹/L.
• Carmustine (BiCNU) 300 mg/m² IV once on day -7
• Etoposide (Vepesid) 100 mg/m² IV once per day on days -6 to -3
• Cytarabine (Cytosar) 200 mg/m² IV Q12H on days -6 to -3
• Melphalan (Alkeran) 140 mg/m² IV once on day -2

Supportive medications

• "According to standard use"

References

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

Low-dose conditioning for cellular therapy

Cyclophosphamide & Fludarabine

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Regimen

Study	Evidence
Locke et al. 2017 (ZUMA-1)	Phase I

Chemotherapy

• Cyclophosphamide (Cytoxan) 500 mg/m² IV once per day on days -6 to -4
• Fludarabine (Fludara) 30 mg/m² IV once per day on days -6 to -4

References

1. Phase 1: Locke FL, Neelapu SS, Bartlett NL, Siddiqi T, Chavez JC, Hosing CM, Ghobadi A, Budde LE, Bot A, Rossi JM, Jiang Y, Xue AX, Elias M, Aycock J, Wiezorek J, Go WY. Phase 1 results of ZUMA-1: A multicenter study of KTE-C19 anti-CD19 CAR T cell therapy in refractory aggressive lymphoma. Mol Ther. 2017 Jan 4;25(1):285-295. Epub 2017 Jan 4. link to original article contains verified protocol PubMed