Staging page

Section editor
	Talal Hilal, MD University of Mississippi Jackson, MS THilalMD

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 before HSCT is day -1, the day of HSCT is day 0, and the day after HSCT is day +1.

0 regimens on this page 0 variants on this page

High dose therapy conditioning regimens, all lines of therapy

BCNU/TT

BCNU/TT: BCNU (Carmustine), ThioTepa

Regimen variant #1

Study	Evidence
Illerhaus et al. 2006	Phase 2

Chemotherapy

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

Supportive therapy

• 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 variant #2

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

Chemotherapy

• Carmustine (BCNU) 400 mg/m² IV once on day 1
• Thiotepa (Thioplex) 5 mg/kg (route not specified) twice per day 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 dosing details in manuscript 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 dosing details in manuscript PubMed

BEAC

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

Regimen variant #1

Study	Evidence
Geisler et al. 2008 (NLG MCL2)	Phase 2

Chemotherapy

• Carmustine (BCNU) 300 mg/m² IV once on day 1
• Etoposide (Vepesid) 100 mg/m² IV twice per day on days 2 to 5
• Cytarabine (Ara-C) 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 variant #2

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Philip et al. 1995 (PARMA)	1987-1994	Phase 3 (E-esc)	DHAP x 4	Seems to have superior OS

Chemotherapy

• Carmustine (BCNU) 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 (Ara-C) 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 therapy

• 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 variant #3

Study	Evidence
Philip et al. 1991 (Parma)	Phase 2

Chemotherapy

• Carmustine (BCNU) 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 (Ara-C) 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 therapy

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

Stem cells re-infused on day 0

References

1. PARMA pilot: Philip T, Chauvin F, Armitage J, Bron D, Hagenbeek A, Biron P, Spitzer G, Velasquez W, Weisenburger DD, Fernandez-Ranada J, Somers R, Rizzoli V, Harousseau JL, Sotto JJ, Cahn JY, Guilhot F, Biggs J, Sonneveld P, Misset JL, Manna A, Jagannath S, Guglielmi C, Chevreau C, Delmer A, Santini G, Coiffier B. Parma international protocol: pilot study of DHAP followed by involved-field radiotherapy and BEAC with autologous bone marrow transplantation. Blood. 1991 Apr 1;77(7):1587-92. link to original article contains dosing details in manuscript PubMed
2. PARMA: Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, Coiffier B, Biron P, Mandelli F, Chauvin F. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med. 1995 Dec 7;333(23):1540-5. link to original article contains dosing details in manuscript 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 dosing details in abstract PubMed
4. NLG MCL2: 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 dosing details in manuscript PubMed

BEAM

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

Regimen variant #1, 300/100q12/100q12/140 with 24-hour rest

Study	Evidence
Alvarnas et al. 2016 (BMT CTN 0803/AMC 071)	Phase 2

Chemotherapy

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

Regimen variant #2, 300/100q12/100q12/140 with 48-hour rest

Study	Evidence
Van 't Veer et al. 2008 (HOVON 45)	Phase 2

Chemotherapy

• Carmustine (BCNU) 300 mg/m² IV once on day -7
• Etoposide (Vepesid) 100 mg/m² IV every 12 hours on days -6 to -3 (total dose: 800 mg/m²)
• Cytarabine (Ara-C) 100 mg/m² IV every 12 hours on days -6 to -3 (total dose: 800 mg/m²)
• Melphalan (Alkeran) 140 mg/m² IV once on day -2

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

Study	Evidence
Philip et al. 1987	Non-randomized

Paper did not specify which day peripheral blood stem cells were administered. This trial is of important historic interest because it indicated that patients with less than a partial response did worse than those with PR or better.

Chemotherapy

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

Regimen variant #4, 300/100q12/200q12/140

Study	Evidence
Abrey et al. 2003	Phase 2
Stewart et al. 2006	Phase 2
d'Amore et al. 2012 (NLG-T-01)	Non-randomized

Chemotherapy

• Carmustine (BCNU) 300 mg/m² IV once on day -6
• Etoposide (Vepesid) 100 mg/m² IV every 12 hours on days -5 to -2 (total dose: 800 mg/m²)
• Cytarabine (Ara-C) 200 mg/m² IV every 12 hours on days -5 to -2 (total dose: 1600 mg/m²)
• Melphalan (Alkeran) 140 mg/m² IV once on day -1

Supportive therapy

• (described in some publications)
• 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 twice per day on Monday and Thursdays, until 6 months after BEAM

While ANC less than 500/uL:

• Ciprofloxacin (Cipro) 500 mg PO twice per day
• Antifungal prophylaxis with one of the following:
  • Fluconazole (Diflucan) 100 mg PO once per day
  • Mycostatin (Nystatin) 500,000 units swish & swallow four times per day
• Acyclovir (Zovirax) 400 mg PO three times per day

Stem cells re-infused on day 0

Regimen variant #5, 300/100q12/400/140

Study	Evidence
Geisler et al. 2008 (NLG MCL2)	Phase 2

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

Chemotherapy

• Carmustine (BCNU) 300 mg/m² IV once on day 1
• Etoposide (Vepesid) 100 mg/m² IV twice per day on days 2 to 5 (total dose: 800 mg/m²)
• Cytarabine (Ara-C) 400 mg/m² IV once per day on days 2 to 5
• Melphalan (Alkeran) 140 mg/m² IV once on day 6

Regimen variant #6, 300/150q12/200q12/140

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Josting et al. 2005	NR	Phase 2
Schmitz et al. 2002 (GHSG HD-R1)	1993-1997	Randomized (E-esc)	DexaBEAM	Seems to have superior FFTF

Note: Josting et al. 2005 did not specify which day peripheral blood stem cells were administered.

Chemotherapy

• Carmustine (BCNU) 300 mg/m² IV once on day -7
• Etoposide (Vepesid) 150 mg/m² IV every 12 hours on days -7 to -4 (total dose: 1200 mg/m²)
• Cytarabine (Ara-C) 200 mg/m² IV every 12 hours on days -7 to -4 (total dose: 1600 mg/m²)
• Melphalan (Alkeran) 140 mg/m² IV once on day -3

Stem cells re-infused on day 0

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

Study	Evidence
Colombat et al. 2006	Phase 2

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

Chemotherapy

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

Regimen variant #8, 300/200/200/140

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

Chemotherapy

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

Regimen variant #9, 300/200/200q12/140 with 24 hour rest

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Shimoni et al. 2012 (SHEBA-07-4466-AN-CTIL)	NR	Randomized Phase 2 (C)	Z-BEAM	Seems to have inferior OS
van Imhoff et al. 2016 (ORCHARRD)	NR	Non-randomized portion of RCT

Chemotherapy

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

Supportive therapy

• 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 variant #10, 300/200/200q12/140 with 48 hour rest

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Schmitz et al. 2021 (MYS-07-HMO-CTIL)	2011-2014	Phase 3 (C)	Fludarabine, Busulfan, Cyclophosphamide, then allo HSCT	Did not meet primary endpoint of EFS36

Chemotherapy

• Carmustine (BCNU) 300 mg/m² IV once on day -7
• Etoposide (Vepesid) 200 mg/m² IV once per day on days -6 to -3
• Cytarabine (Ara-C) 200 mg/m² IV every 12 hours on days -6 to -3 (total dose: 1600 mg/m²)
• Melphalan (Alkeran) 140 mg/m² IV once on day -2

Regimen variant #11, 300/200q12/200q12/140

Study	Evidence
Zinzani et al. 2003	Retrospective

Chemotherapy

• Carmustine (BCNU) 300 mg/m² IV once on day -7
• Etoposide (Vepesid) 200 mg/m² IV twice per day on days -6 to -3 (total dose: 1600 mg/m²)
• Cytarabine (Ara-C) 200 mg/m² IV twice per day on days -6 to -3 (total dose: 1600 mg/m²)
• Melphalan (Alkeran) 140 mg/m² IV once on day -2

Regimen variant #12, 300/200/400/140

Study	Evidence
Jo et al. 2008	Retrospective

Chemotherapy

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

Supportive therapy

• 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"

References

1. Philip T, Armitage JO, Spitzer G, Chauvin F, Jagannath S, Cahn JY, Colombat P, Goldstone AH, Gorin NC, Flesh M, Laporte JP, Maraninchi D, Pico J, Bosly A, Anderson C, Schots R, Biron P, Cabanillas F, Dicke K. High-dose therapy and autologous bone marrow transplantation after failure of conventional chemotherapy in adults with intermediate-grade or high-grade non-Hodgkin's lymphoma. N Engl J Med. 1987 Jun 11;316(24):1493-8. link to original article contains dosing details in manuscript PubMed
2. GHSG HD-R1: Schmitz N, Pfistner B, Sextro M, Sieber M, Carella AM, Haenel M, Boissevain F, Zschaber R, Müller P, Kirchner H, Lohri A, Decker S, Koch B, Hasenclever D, Goldstone AH, Diehl V; German Hodgkin's Lymphoma Study Group; Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin's disease: a randomised trial. Lancet. 2002 Jun 15;359(9323):2065-71. link to original article contains dosing details in manuscript 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 dosing details in manuscript PubMed
4. 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 dosing details in manuscript PubMed
5. Retrospective: 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
6. 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 dosing details in abstract PubMed
7. 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 dosing details in abstract PubMed content property of HemOnc.org
8. 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; GOELAMS. 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 dosing details in manuscript PubMed
9. 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 dosing details in abstract PubMed
10. NLG MCL2: 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 dosing details in manuscript PubMed ISRCTN87866680
11. HOVON 45: 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 dosing details in manuscript PubMed
12. CORAL: Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Brière J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. Epub 2010 Jul 26. Erratum in: J Clin Oncol. 2012 May 20;30(15):1896. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00137995
13. SHEBA-07-4466-AN-CTIL: Shimoni A, Avivi I, Rowe JM, Yeshurun M, Levi I, Or R, Patachenko P, Avigdor A, Zwas T, Nagler A. A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma. Cancer. 2012 Oct 1;118(19):4706-14. Epub 2012 Jan 17. link to original article contains dosing details in manuscript PubMed NCT00491491
14. NLG-T-01: d'Amore F, Relander T, Lauritzsen GF, Jantunen E, Hagberg H, Anderson H, Holte H, Österborg A, Merup M, Brown P, Kuittinen O, Erlanson M, Østenstad B, Fagerli UM, Gadeberg OV, Sundström C, Delabie J, Ralfkiaer E, Vornanen M, Toldbod HE. Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma: NLG-T-01. J Clin Oncol. 2012 Sep 1;30(25):3093-9. Epub 2012 Jul 30. link to original article contains dosing details in manuscript PubMed NCT00791947
15. GELTAMO-2006: Pardal E, Coronado M, Martín A, Grande C, Marín-Niebla A, Panizo C, Bello JL, Conde E, Hernández MT, Arranz R, Bargay J, González-Barca E, Pérez-Ceballos E, Montes-Moreno S, Caballero MD. Intensification treatment based on early FDG-PET in patients with high-risk diffuse large B-cell lymphoma: a phase II GELTAMO trial. Br J Haematol. 2014 Nov;167(3):327-36. Epub 2014 Jul 28. link to original article contains dosing details in manuscript PubMed NCT013611091
16. BMT CTN 0803/AMC 071: 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 dosing details in manuscript link to PMC article PubMed NCT01141712
17. ORCHARRD: van Imhoff GW, McMillan A, Matasar MJ, Radford J, Ardeshna KM, Kuliczkowski K, Kim W, Hong X, Goerloev JS, Davies A, Barrigón MD, Ogura M, Leppä S, Fennessy M, Liao Q, van der Holt B, Lisby S, Hagenbeek A. Ofatumumab versus rituximab salvage chemoimmunotherapy in relapsed or refractory diffuse large B-cell lymphoma: the ORCHARRD study. J Clin Oncol. 2017 Feb 10;35(5):544-51. Epub 2016 Dec 28. link to original article link to data supplement contains dosing details in supplement PubMed NCT01014208
18. MYS-07-HMO-CTIL: Schmitz N, Truemper L, Bouabdallah K, Ziepert M, Leclerc M, Cartron G, Jaccard A, Reimer P, Wagner E, Wilhelm M, Sanhes L, Lamy T, de Leval L, Rosenwald A, Roussel M, Kroschinsky F, Lindemann W, Dreger P, Viardot A, Milpied N, Gisselbrecht C, Wulf G, Gyan E, Gaulard P, Bay JO, Glass B, Poeschel V, Damaj G, Sibon D, Delmer A, Bilger K, Banos A, Haenel M, Dreyling M, Metzner B, Keller U, Braulke F, Friedrichs B, Nickelsen M, Altmann B, Tournilhac O. A randomized phase 3 trial of autologous vs allogeneic transplantation as part of first-line therapy in poor-risk peripheral T-NHL. Blood. 2021 May 13;137(19):2646-2656. link to original article contains dosing details in manuscript PubMed NCT00984412

BeEAM

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

Regimen

Study	Evidence
Visani et al. 2011	Phase 1/2

Chemotherapy

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

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 dosing details in manuscript PubMed EudraCT 2008-002736-15

Bortezomib & Melphalan

Bor-HDM: Bortezomib, High Dose Melphalan

Regimen variant #1, HDM 140 mg/m²

Study	Evidence
Sanchorawala et al. 2015 (X05292)	Phase 2

Targeted therapy

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

Chemotherapy

• Melphalan (Alkeran) 70 mg/m² IV once per day on days -2 & -1

Stem cells re-infused on day 0

Regimen variant #2, HDM 200 mg/m²

Study	Evidence
Roussel et al. 2009	Phase 2
Sanchorawala et al. 2015 (X05292)	Phase 2

Targeted therapy

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

Chemotherapy

• Melphalan (Alkeran) 100 mg/m² IV once per day on days -2 & -1
  • Roussel et al. 2009 gave as a single 200 mg/m² dose on day -2

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. 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 dosing details in manuscript PubMed NCT00642395
2. X05292: Sanchorawala V, Brauneis D, Shelton AC, Lo S, Sun F, Sloan JM, Quillen K, Seldin DC. Induction therapy with bortezomib followed by bortezomib-high dose melphalan and stem cell transplantation for light chain amyloidosis: Results of a prospective clinical trial. Biol Blood Marrow Transplant. 2015 Aug;21(8):1445-51. Epub 2015 Apr 6. link to original article contains dosing details in manuscript PubMed NCT01083316

Busulfan & Cyclophosphamide

Regimen variant #1, 16/120

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Vellenga et al. 2011 (HOVON-SAKK AML-29/AML-42)	1995-2006	Phase 3 (E-esc)	Etoposide & Mitoxantrone	Might have superior RFS

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

Regimen variant #2, 16/200

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Ravindranath et al. 1996	1988-1993	Phase 3 (E-esc)	Intensive chemotherapy	Did not meet primary endpoint of EFS36

Chemotherapy

• Busulfan (Myleran) 1 mg/kg PO every 6 hours on days -9 to -6
• Cyclophosphamide (Cytoxan) 50 mg/kg IV once per day on days -5 to -2

References

1. Ravindranath Y, Yeager AM, Chang MN, Steuber CP, Krischer J, Graham-Pole J, Carroll A, Inoue S, Camitta B, Weinstein HJ; Pediatric Oncology Group. Autologous bone marrow transplantation versus intensive consolidation chemotherapy for acute myeloid leukemia in childhood. N Engl J Med. 1996 May 30;334(22):1428-34. link to original article contains dosing details in manuscript PubMed
2. HOVON-SAKK AML-29/AML-42: 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; Swiss Group for Clinical Cancer Research. 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 dosing details in manuscript PubMed

Busulfan & Melphalan

BuMel: Busulfan & Melphalan

Regimen variant #1, PO busulfan (12 mg/kg)

Study	Evidence
Yanada et al. 2013 (JALSG APL205R)	Phase 2

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

Chemotherapy

• Busulfan (Myleran) 1 mg/kg PO every 6 hours on days -6 to -4 (total dose of 12 mg/kg)
• Melphalan (Alkeran) 70 mg/m² IV bolus once per day on days -3 & -2

Stem cells re-infused on day 0

Regimen variant #2, PO busulfan (16 mg/kg), mel 140 mg/m²

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Atra et al. 1997	NR	Phase 2, <20 pts
Whelan et al. 2018 (R2Loc)	2000-2015	Phase 3 (E-esc)	VAI	Seems to have superior OS

This regimen was evaluated in the setting of poor risk Ewing sarcoma.

Chemotherapy

• Busulfan (Myleran) 1 mg/kg PO every 6 hours on days -5 to -2 (total dose of 16 mg/kg)
• Melphalan (Alkeran) 140 mg/m² IV once on day -1

Stem cells re-infused on day 0

Regimen variant #3, PO busulfan (16 mg/kg), mel 160 mg/m²

Study	Years of enrollment	Evidence
Atra et al. 1997	NR	Phase 2, <20 pts

This regimen was evaluated in the setting of poor risk Ewing sarcoma.

Chemotherapy

• Busulfan (Myleran) 1 mg/kg PO every 6 hours on days -5 to -2 (total dose of 16 mg/kg)
• Melphalan (Alkeran) 160 mg/m² IV once on day -1

Stem cells re-infused on day 0

Regimen variant #4, IV busulfan

Study	Evidence
Strauss et al. 2003	Phase 2

This regimen was evaluated in the setting of metastatic Ewing 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

Stem cells re-infused on day 0

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 contains dosing details in manuscript 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 dosing details in manuscript PubMed
3. JALSG APL205R: 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 dosing details in manuscript PubMed NCT01908621
4. R2Loc: Whelan J, Le Deley MC, Dirksen U, Le Teuff G, Brennan B, Gaspar N, Hawkins DS, Amler S, Bauer S, Bielack S, Blay JY, Burdach S, Castex MP, Dilloo D, Eggert A, Gelderblom H, Gentet JC, Hartmann W, Hassenpflug WA, Hjorth L, Jimenez M, Klingebiel T, Kontny U, Kruseova J, Ladenstein R, Laurence V, Lervat C, Marec-Berard P, Marreaud S, Michon J, Morland B, Paulussen M, Ranft A, Reichardt P, van den Berg H, Wheatley K, Judson I, Lewis I, Craft A, Juergens H, Oberlin O; Euro-EWING-99 and EWING-2008 Investigators. High-dose chemotherapy and blood autologous stem-cell rescue compared with standard chemotherapy in localized high-risk Ewing sarcoma: results of Euro-EWING99 and Ewing-2008. J Clin Oncol. 2018 Nov 1;36(31):3110-9. Epub 2018 Sep 6. link to original article contains dosing details in supplement link to PMC article PubMed NCT00020566

Bu/TT

Bu/TT: Busulfan, ThioTepa

Regimen

Study	Evidence
Montemurro et al. 2007 (OSHO-53)	Phase 2

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. OSHO-53: 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 dosing details in manuscript PubMed

Bu/TT/Cy

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

Regimen

Study	Evidence
Omuro et al. 2015 (MSK 04-129)	Phase 2

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. MSK 04-129: 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 dosing details in manuscript link to PMC article PubMed NCT00596154
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

CBV

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

Regimen variant #1, 100/300/60, some BSA-based

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Stiff et al. 2013 (SWOG S9704)	1999-2007	Phase 3 (E-esc)	R-CHOP x 8	Superior PFS

Chemotherapy

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

Stem cells re-infused on day 0

Regimen variant #2, 100/15/60, all weight-based

Study	Evidence
Stiff et al. 1998	Phase 2
Damon et al. 2009 (CALGB 59909)	Phase 2

Note: Stiff et al. 1998 based BCNU dosing on ideal body weight, whereas CALGB 59909 capped based on BSA, as described below.

Chemotherapy

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

Supportive therapy

• 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 three times per day, starting on day -2, to continue until 1 year after HSCT
• Trimethoprim-Sulfamethoxazole (Bactrim DS) 160/800 mg PO twice per day on Saturday and Sunday, to continue until 3 months after HSCT

Additional considerations

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

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

Stem cells re-infused on day 0

Regimen variant #3, 1500/300/250, all BSA-based

Study	Evidence
Zinzani et al. 2003	Retrospective

Chemotherapy

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

Stem cells re-infused on day 0

Regimen variant #4, 1800/600/400

Study	Evidence
Reece et al. 1994	Phase 2, <20 pts

Note: the lower of IBW or ABW was used in the dosing calculations.

Chemotherapy

• Cyclophosphamide (Cytoxan) 1800 mg/m² IV over 2 hours once per day on days -7 to -4
• Carmustine (BCNU) 600 mg/m² IV once on day -3
• Etoposide (Vepesid) 400 mg/m² IV over 60 minutes every 12 hours on days -7 to -5

Stem cells re-infused on day 0

References

1. Reece DE, Connors JM, Spinelli JJ, Barnett MJ, Fairey RN, Klingemann HG, Nantel SH, O'Reilly S, Shepherd JD, Sutherland HJ, Voss N, Chan KW, Phillips GL. 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 contains dosing details in manuscript PubMed
2. Stiff PJ, Dahlberg S, Forman SJ, McCall AR, Horning SJ, Nademanee AP, Blume KG, LeBlanc M, Fisher RI; SWOG. 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 dosing details in manuscript 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 dosing details in manuscript PubMed
4. CALGB 59909: 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 dosing details in abstract link to PMC article PubMed NCT00020943
5. SWOG S9704: Stiff PJ, Unger JM, Cook JR, Constine LS, Couban S, Stewart DA, Shea TC, Porcu P, Winter JN, Kahl BS, Miller TP, Tubbs RR, Marcellus D, Friedberg JW, Barton KP, Mills GM, LeBlanc M, Rimsza LM, Forman SJ, Fisher RI. Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. N Engl J Med. 2013 Oct 31;369(18):1681-90. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00004031

CBV-Mx

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

Regimen

Study	Evidence
Morschhauser et al. 2008 (GELA/SFGM H96)	Non-randomized

Chemotherapy

• Cyclophosphamide (Cytoxan) 1500 mg/m²/day IV on days -7 to -4
• Carmustine (BCNU) 300 mg/m² IV once on day -4
• Etoposide (Vepesid) 250 mg/m²/day IV on days -7 to -4
• Mitoxantrone (Novantrone) 30 mg/m² IV once on day -8

Stem cells re-infused on day 0

References

1. GELA/SFGM H96: Morschhauser F, Brice P, Fermé C, Diviné M, Salles G, Bouabdallah R, Sebban C, Voillat L, Casasnovas O, Stamatoullas A, Bouabdallah K, André M, Jais JP, Cazals-Hatem D, Gisselbrecht C; GELA; SFGM. Risk-adapted salvage treatment with single or tandem autologous stem-cell transplantation for first relapse/refractory Hodgkin's lymphoma: results of the prospective multicenter H96 trial by the GELA/SFGM study group. J Clin Oncol. 2008 Dec 20;26(36):5980-7. Epub 2008 Nov 17. link to original article contains dosing details in manuscript PubMed
   1. Update: Sibon D, Morschhauser F, Resche-Rigon M, Ghez D, Dupuis J, Marçais A, Deau-Fischer B, Bouabdallah R, Sebban C, Salles G, Brice P. Single or tandem autologous stem-cell transplantation for first-relapsed or refractory Hodgkin lymphoma: 10-year follow-up of the prospective H96 trial by the LYSA/SFGM-TC study group. Haematologica. 2016 Apr;101(4):474-81. Epub 2015 Dec 31. link to original article link to PMC article PubMed

CHUT

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Biron et al. 2007 (Pegase 03)	1995-2001	Phase 3 (E-esc)	No further treatment	Superior DFS

No longer used, but of historical interest.

Chemotherapy

• Cyclophosphamide (Cytoxan) 6000 mg/m²
• Thiotepa (Thioplex) 800 mg/m²

References

1. Pegase 03: Biron P, Durand M, Roché H, Delozier T, Battista C, Fargeot P, Spaeth D, Bachelot T, Poiget E, Monnot F, Tanguy ML, Curé H. Pegase 03: a prospective randomized phase III trial of FEC with or without high-dose thiotepa, cyclophosphamide and autologous stem cell transplantation in first-line treatment of metastatic breast cancer. Bone Marrow Transplant. 2008 Mar;41(6):555-62. Epub 2007 Nov 26. link to original article PubMed NCT00002870

CTCb

CTCb: Cyclophosphamide, Thiotepa, Carboplatin

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Eder et al. 1990	1987-1988	Phase 1/2
Stadtmauer et al. 2000	1990-1997	Phase 3 (E-esc)	CMF	Did not meet primary endpoint of OS
Rodenhuis et al. 1998	1991-1995	Randomized Phase 2 (E-esc)	Standard adjuvant therapy	Did not meet primary endpoints of DFS/OS
Rodenhuis et al. 2003 (Dutch National Study)	1993-1999	Phase 3 (E-esc)	FEC x 5	Might have superior RFS

No longer used, but of historical interest.

Chemotherapy

• Cyclophosphamide (Cytoxan) 6000 mg/m²
• Thiotepa (Thioplex) 480 mg/m²
• Carboplatin (Paraplatin) 1600 mg/m²

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. Rodenhuis S, Richel DJ, van der Wall E, Schornagel JH, Baars JW, Koning CC, Peterse JL, Borger JH, Nooijen WJ, Bakx R, Dalesio O, Rutgers E. Randomised trial of high-dose chemotherapy and haemopoietic progenitor-cell support in operable breast cancer with extensive axillary lymph-node involvement. Lancet. 1998 Aug 15;352(9127):515-21. link to original article PubMed
3. 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; Philadelphia Bone Marrow Transplant Group. Conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer. N Engl J Med. 2000 Apr 13;342(15):1069-76. link to original article PubMed
4. Dutch National Study: Rodenhuis S, Bontenbal M, Beex LV, Wagstaff J, Richel DJ, Nooij MA, Voest EE, Hupperets P, van Tinteren H, Peterse HL, TenVergert EM, de Vries EG; Netherlands Working Party on Autologous Transplantation in Solid Tumors. High-dose chemotherapy with hematopoietic stem-cell rescue for high-risk breast cancer. N Engl J Med. 2003 Jul 3;349(1):7-16. link to original article PubMed NCT03087409

Cyclophosphamide, Etoposide, TBI

Regimen

Study	Evidence
Stiff et al. 1998	Phase 2

Chemotherapy

• 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

Radiotherapy

• 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 therapy

• 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; SWOG. 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 dosing details in manuscript PubMed

Cyclophosphamide & TBI

Cy/TBI: Cyclophosphamide & Total Body Irradiation

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Phillips et al. 1984	1977-1982	Non-randomized
Takvorian et al. 1987	1982-1987	Non-randomized
Schouten et al. 2003 (CUP)	1993-1997	Phase 3 (E-esc)	CHOP x 3	Might have superior OS
Dreyling et al. 2004	1996-2004	Phase 3 (E-esc)	Interferon alfa maintenance	Seems to have superior PFS
Reimer et al. 2004	2000-2002	Phase 2

Chemotherapy

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

Radiotherapy

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

References

1. Phillips GL, Herzig RH, Lazarus HM, Fay JW, Wolff SN, Mill WB, Lin H, Thomas PR, Glasgow GP, Shina DC, Herzig GP. Treatment of resistant malignant lymphoma with cyclophosphamide, total body irradiation, and transplantation of cryopreserved autologous marrow. N Engl J Med. 1984 Jun 14;310(24):1557-61. link to original article PubMed
2. Takvorian T, Canellos GP, Ritz J, Freedman AS, Anderson KC, Mauch P, Tarbell N, Coral F, Daley H, Yeap B, Schlossman SF, Nadler LM. Prolonged disease-free survival after autologous bone marrow transplantation in patients with non-Hodgkin's lymphoma with a poor prognosis. N Engl J Med. 1987 Jun 11;316(24):1499-505. link to original article PubMed
3. CUP: Schouten HC, Qian W, Kvaloy S, Porcellini A, Hagberg H, Johnsen HE, Doorduijn JK, Sydes MR, Kvalheim G. High-dose therapy improves progression-free survival and survival in relapsed follicular non-Hodgkin's lymphoma: results from the randomized European CUP trial. J Clin Oncol. 2003 Nov 1;21(21):3918-27. Epub 2003 Sep 29. link to original article PubMed
4. Reimer P, Schertlin T, Rüdiger T, Geissinger E, Roth S, Kunzmann V, Weissinger F, Nerl C, Schmitz N, Müller-Hermelink HK, Wilhelm M. Myeloablative radiochemotherapy followed by autologous peripheral blood stem cell transplantation as first-line therapy in peripheral T-cell lymphomas: first results of a prospective multicenter study. Hematol J. 2004;5(4):304-11. link to original article PubMed
   1. Update: Reimer P, Rüdiger T, Geissinger E, Weissinger F, Nerl C, Schmitz N, Engert A, Einsele H, Müller-Hermelink HK, Wilhelm M. Autologous stem-cell transplantation as first-line therapy in peripheral T-cell lymphomas: results of a prospective multicenter study. J Clin Oncol. 2009 Jan 1;27(1):106-13. Epub 2008 Nov 24. link to original article contains dosing details in manuscript PubMed
5. 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

Etoposide & TBI: Etoposide & Total Body Irradiation

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Rowe et al. 2005 (MRC UKALL XII/ECOG E2993)	1993-2003	Phase 3 (E-esc)	International ALL Trial consolidation, then POMP 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.

Chemotherapy

• Etoposide (Vepesid) 60 mg/kg IV once on day -3

Radiotherapy

• Total body irradiation (TBI) 220 cGy twice per day in 6 fractions on days –6 to –4 (total dose: 1320 cGy)

References

1. MRC UKALL XII/ECOG E2993: 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 dosing details in manuscript PubMed NCT00002514
   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 dosing details in manuscript link to PMC article PubMed

FEAM

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

Regimen

Study	Evidence
Musso et al. 2009	Phase 2
Musso et al. 2015	Phase 2

Chemotherapy

• Fotemustine (Muphoran)
• Etoposide (Vepesid)
• Cytarabine (Ara-C)
• Melphalan (Alkeran)

References

1. Musso M, Scalone R, Marcacci G, Lanza F, Di Renzo N, Cascavilla N, Di Bartolomeo P, Crescimanno A, Perrone T, Pinto A. Fotemustine plus etoposide, cytarabine and melphalan (FEAM) as a new conditioning regimen for lymphoma patients undergoing auto-SCT: a multicenter feasibility study. Bone Marrow Transplant. 2010 Jul;45(7):1147-53. Epub 2009 Nov 9. link to original article PubMed
2. Musso M, Messina G, Di Renzo N, Di Carlo P, Vitolo U, Scalone R, Marcacci G, Scalzulli PR, Moscato T, Matera R, Crescimanno A, Santarone S, Orciuolo E, Merenda A, Pavone V, Pastore D, Donnarumma D, Carella AM, Ciochetto C, Cascavilla N, Mele A, Lanza F, Di Nicola M, Bonizzoni E, Pinto A. Improved outcome of patients with relapsed/refractory Hodgkin lymphoma with a new fotemustine-based high-dose chemotherapy regimen. Br J Haematol. 2016 Jan;172(1):111-21. Epub 2015 Oct 12. link to original article link to PMC article PubMed

LEED

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

Glucocorticoid therapy

• Dexamethasone (Decadron) 40 mg IV once per day on days -4 to -1

References

1. ORCHARRD: van Imhoff GW, McMillan A, Matasar MJ, Radford J, Ardeshna KM, Kuliczkowski K, Kim W, Hong X, Goerloev JS, Davies A, Barrigón MD, Ogura M, Leppä S, Fennessy M, Liao Q, van der Holt B, Lisby S, Hagenbeek A. Ofatumumab versus rituximab salvage chemoimmunotherapy in relapsed or refractory diffuse large B-cell lymphoma: the ORCHARRD study. J Clin Oncol. 2017 Feb 10;35(5):544-51. Epub 2016 Dec 28. link to original article link to data supplement contains dosing details in supplement PubMed NCT01014208

Melphalan & TBI

Melphalan & TBI: Melphalan & Total Body Irradiation

Regimen

Study	Evidence
Gressin et al. 2010 (GOELAMS LM1996)	Phase 2
Gressin et al. 2010 (GOELAMS LM2001)	Phase 2

Chemotherapy

• Melphalan (Alkeran) 140 mg/m² IV once (day not specified)

Radiotherapy

• Total body irradiation (TBI) : 800 cGy in 4 fractions (days not specified)

References

1. GOELAMS LM1996: 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; GOELAMS. 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
2. GOELAMS LM2001: 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; GOELAMS. 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 NCT00285389

Melphalan monotherapy

Regimen

Study	Evidence
Skinner et al. 2004	Phase 2

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) by the following criteria:
  • 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: 100 mg/m² IV once per day on days 1 & 2
  • 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: 70 mg/m² IV once per day on days 1 & 2

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 dosing details in manuscript 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; IFM. 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 dosing details in abstract PubMed

R-BEAM

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

Regimen variant #1, 500/300/1600/1600/140

Study	Evidence
Le Gouill et al. 2017 (LyMa)	Non-randomized portion of RCT

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

Targeted therapy

• Rituximab (Rituxan) 500 mg/m² IV once on day -8

Chemotherapy

• Carmustine (BCNU) 300 mg/m² IV once on day -7
• Etoposide (Vepesid) 400 mg/m² IV once per day on days -6 to -3
• Cytarabine (Ara-C) 400 mg/m² IV once per day on days -6 to -3
• Melphalan (Alkeran) 140 mg/m² IV once on day -2

Stem cells re-infused on day 0

Regimen variant #2, 750/300/800/800/140

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Vose et al. 2013 (BMT CTN 0401)	2006-2009	Phase 3 (C)	B-BEAM	Did not meet primary endpoint of PFS24

Targeted therapy

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

Chemotherapy

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

Stem cells re-infused on day 0

Regimen variant #3, 750/300/1600/3200/140

Study	Evidence
Kirschey et al. 2014 (Mz-135)	Phase 2

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

Targeted therapy

• Rituximab (Rituxan) 375 mg/m² IV once per day on days -8 & -2

Chemotherapy

• Carmustine (BCNU) 300 mg/m² IV once on day -7
• Etoposide (Vepesid) 200 mg/m² IV twice per day on days -6 to -3
• Cytarabine (Ara-C) 400 mg/m² IV twice per day on days -6 to -3
• Melphalan (Alkeran) 140 mg/m² IV once on day -2

Stem cells re-infused on day 0

References

1. BMT CTN 0401: Vose JM, Carter S, Burns LJ, Ayala E, Press OW, Moskowitz CH, Stadtmauer EA, Mineshi S, Ambinder R, Fenske T, Horowitz M, Fisher R, Tomblyn M. Phase III randomized study of rituximab/carmustine, etoposide, cytarabine, and melphalan (BEAM) compared with iodine-131 tositumomab/BEAM with autologous hematopoietic cell transplantation for relapsed diffuse large B-cell lymphoma: results from the BMT CTN 0401 trial. J Clin Oncol. 2013 May 1;31(13):1662-8. Epub 2013 Mar 11. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00329030
2. Mz-135: Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. link to original article contains dosing details in manuscript PubMed NCT02099292
3. LyMa: Le Gouill S, Thieblemont C, Oberic L, Moreau A, Bouabdallah K, Dartigeas C, Damaj G, Gastinne T, Ribrag V, Feugier P, Casasnovas O, Zerazhi H, Haioun C, Maisonneuve H, Houot R, Jardin F, Van Den Neste E, Tournilhac O, Le Dû K, Morschhauser F, Cartron G, Fornecker LM, Canioni D, Callanan M, Béné MC, Salles G, Tilly H, Lamy T, Gressin R, Hermine O; LYSA. Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma. N Engl J Med. 2017 Sep 28;377(13):1250-1260. link to original article link to protocol contains dosing details in supplement PubMed NCT00921414

R-TBI/Cy

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

Regimen

Study	Evidence
Kirschey et al. 2014 (Mz-135)	Phase 2

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

Targeted therapy

• Rituximab (Rituxan) 375 mg/m² IV once per day on days -8 & -2

Chemotherapy

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

Radiotherapy

• Total body irradiation (TBI) with a total dose of 12 Gy over 3 days (days -6 to -4) in fractions

References

1. Mz-135: Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. link to original article contains dosing details in manuscript PubMed NCT02099292

TAM6

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

Regimen

Study	Evidence
Delarue et al. 2012	Phase 2

Radiotherapy

• Total body irradiation (TBI) with a total dose of 10 Gy over 3 days using twice per day fractions

Chemotherapy

• Cytarabine (Ara-C) 1500 mg/m² IV every 12 hours for 2 days (total dose: 6000 mg/m²)
• Melphalan (Alkeran) 140 mg/m² IV once

Supportive therapy

"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; Groupe d'Etude des Lymphomes de l'Adulte. 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 dosing details in manuscript PubMed

TBI

TBI: Total Body Irradiation

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
McGovern et al. 1959	1957-1958	Pilot
Stiff et al. 2013 (SWOG S9704)	1999-2007	Phase 3 (E-esc)	R-CHOP x 8	Superior PFS

Radiotherapy

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

References

1. McGovern JJ Jr, Russell PS, Atkins L, Webster EW. Treatment of terminal leukemic relapse by total-body irradiation and intravenous infusion of stored autologous bone marrow obtained during remission. N Engl J Med. 1959 Apr 2;260(14):675-83. link to original article PubMed
2. SWOG S9704: Stiff PJ, Unger JM, Cook JR, Constine LS, Couban S, Stewart DA, Shea TC, Porcu P, Winter JN, Kahl BS, Miller TP, Tubbs RR, Marcellus D, Friedberg JW, Barton KP, Mills GM, LeBlanc M, Rimsza LM, Forman SJ, Fisher RI. Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. N Engl J Med. 2013 Oct 31;369(18):1681-90. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00004031

V-BEAM

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

Regimen

Study	Evidence
William et al. 2014	Phase 2

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

Targeted therapy

• Bortezomib (Velcade) on days -11, -8, -5, -2

Chemotherapy

• Carmustine (BCNU)
• Etoposide (Vepesid)
• Cytarabine (Ara-C)
• 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

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

Regimen variant #1

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Shimoni et al. 2012 (SHEBA-07-4466-AN-CTIL)	NR	Randomized Phase 2 (E-esc)	BEAM	Seems to have superior OS
Briones et al. 2013 (GELTAMO Z-BEAM LDCGB)	2008-2010	Phase 2

Targeted therapy

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

Radioconjugate therapy

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

Chemotherapy

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

Supportive therapy

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

Stem cells re-infused on day 0

Regimen variant #2

Study	Evidence
Fruchart et al. 2014 (ZBEAM2)	Phase 2

Targeted therapy

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

Radioconjugate therapy

• Ibritumomab tiuxetan & Yttrium-90 (Zevalin) 0.4 mCi/kg (maximum dose of 32 mCi) IV once on day -14, given second
  • Dose reduced to 0.3 mCi/kg if platelet count was greater than 100 x 10⁹/L and less than 150 x 10⁹/L.

Chemotherapy

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

Supportive therapy

• "According to standard use"

Stem cells re-infused on day 0

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. SHEBA-07-4466-AN-CTIL: Shimoni A, Avivi I, Rowe JM, Yeshurun M, Levi I, Or R, Patachenko P, Avigdor A, Zwas T, Nagler A. A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma. Cancer. 2012 Oct 1;118(19):4706-14. Epub 2012 Jan 17. link to original article contains dosing details in manuscript PubMed NCT00491491
3. GELTAMO Z-BEAM LDCGB: Briones J, Novelli S, García-Marco JA, Tomás JF, Bernal T, Grande C, Canales MA, Torres A, Moraleda JM, Panizo C, Jarque I, Palmero F, Hernández M, González-Barca E, López D, Caballero D. Autologous stem cell transplantation after conditioning with Yttrium-90 ibritumomab tiuxetan plus beam in refractory non-Hodgkin diffuse large B-cell lymphoma: results of a prospective, multicenter, phase II clinical trial. Haematologica. 2014 Mar;99(3):505-10. Epub 2013 Oct 25. link to original article contains dosing details in manuscript link to PMC article PubMed EudraCT 2007-003198-22
4. ZBEAM2: Fruchart C, Tilly H, Morschhauser F, Ghesquières H, Bouteloup M, Fermé C, Van Den Neste E, Bordessoule D, Bouabdallah R, Delmer A, Casasnovas RO, Ysebaert L, Ciappuccini R, Briere J, Gisselbrecht C. Upfront consolidation combining yttrium-90 ibritumomab tiuxetan and high-dose therapy with stem cell transplantation in poor-risk patients with diffuse large B cell lymphoma. Biol Blood Marrow Transplant. 2014 Dec;20(12):1905-11. Epub 2014 Jul 26. link to original article contains dosing details in manuscript PubMed NCT00689169

Low-dose conditioning regimens for cellular therapy, all lines of therapy

Bendamustine monotherapy

Regimen

Study	Evidence
Schuster et al. 2018 (JULIET)	Phase 2

Note: Lymphodepleting chemotherapy may be omitted if a patient’s white blood cell count is less than or equal to 1 x 10⁹/L within 1 week prior to tisagenlecleucel infusion. This regimen is suggested if a patient experienced a previous grade 4 hemorrhagic cystitis with cyclophosphamide or demonstrates resistance to a previous cyclophosphamide-containing regimen.

Chemotherapy

• Bendamustine 90 mg/m² IV once per day on days 1 & 2

References

1. JULIET: Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, Jäger U, Jaglowski S, Andreadis C, Westin JR, Fleury I, Bachanova V, Foley SR, Ho PJ, Mielke S, Magenau JM, Holte H, Pantano S, Pacaud LB, Awasthi R, Chu J, Anak Ö, Salles G, Maziarz RT; JULIET Investigators. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019 Jan 3;380(1):45-56. Epub 2018 Dec 1. link to original article PubMed NCT02445248
   1. Update: Schuster SJ, Tam CS, Borchmann P, Worel N, McGuirk JP, Holte H, Waller EK, Jaglowski S, Bishop MR, Damon LE, Foley SR, Westin JR, Fleury I, Ho PJ, Mielke S, Teshima T, Janakiram M, Hsu JM, Izutsu K, Kersten MJ, Ghosh M, Wagner-Johnston N, Kato K, Corradini P, Martinez-Prieto M, Han X, Tiwari R, Salles G, Maziarz RT. Long-term clinical outcomes of tisagenlecleucel in patients with relapsed or refractory aggressive B-cell lymphomas (JULIET): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2021 Oct;22(10):1403-1415. Epub 2021 Sep 10. link to original article PubMed

CYVE

CYVE: CYtarabine & VEpeside (Etoposide)

Regimen

Study	Evidence
Maude et al. 2018 (ELIANA)	Phase 2

Note: This regimen is intended for patients with a history of grade 4 hemorrhagic cystitis from cyclophosphamide, or chemorefractory disease in the context of cyclophosphamide. CAR-T cells are to be given 2 to 14 days after completion of lymphodepleting therapy.

Chemotherapy

• Cytarabine (Ara-C) 500 mg/m² IV once per day on days 1 & 2
• Etoposide (Vepesid) 150 mg/m² IV once per day on days 1 to 3

References

1. ELIANA: Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, Bader P, Verneris MR, Stefanski HE, Myers GD, Qayed M, De Moerloose B, Hiramatsu H, Schlis K, Davis KL, Martin PL, Nemecek ER, Yanik GA, Peters C, Baruchel A, Boissel N, Mechinaud F, Balduzzi A, Krueger J, June CH, Levine BL, Wood P, Taran T, Leung M, Mueller KT, Zhang Y, Sen K, Lebwohl D, Pulsipher MA, Grupp SA. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018 Feb 1;378(5):439-448. link to original article link to supplementary protocol contains dosing details in supplement link to PMC article PubMed NCT02435849

FC

FC: Fludarabine & Cyclophosphamide

Regimen variant #1, 250/25

Study	Evidence
Schuster et al. 2018 (JULIET)	Phase 2

Note: Lymphodepleting chemotherapy may be omitted if a patient’s white blood cell count is less than or equal to 1 x 10⁹/L within 1 week prior to tisagenlecleucel infusion.

Chemotherapy

• Fludarabine (Fludara) 25 mg/m² IV once per day on days 1 to 3
• Cyclophosphamide (Cytoxan) 250 mg/m² IV once per day on days 1 to 3

Subsequent treatment

• Infuse tisagenlecleucel 2 to 11 days after completion of the lymphodepleting chemotherapy

Regimen variant #2, 500/30, 2 doses of cyclophosphamide, 4 doses of fludarabine

Study	Evidence
Maude et al. 2018 (ELIANA)	Phase 2

Note: CAR-T cells are to be given 2 to 14 days after completion of lymphodepleting therapy.

Chemotherapy

• Fludarabine (Fludara) 30 mg/m² IV once per day on days 1 to 4
• Cyclophosphamide (Cytoxan) 500 mg/m² IV once per day on days 1 & 2

Regimen variant #3, 500/30, 3 doses of cyclophosphamide, 3 doses of fludarabine

Study	Evidence
Locke et al. 2017 (ZUMA-1)	Phase 1/2

Chemotherapy

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

References

1. ZUMA-1: Locke FL, Neelapu SS, Bartlett NL, Siddiqi T, Chavez JC, Hosing CM, Ghobadi A, Budde LE, Bot A, Rossi JM, Jiang Y, Xue AX, Elias M, Aycock J, Wiezorek J, Go WY. Phase 1 results of ZUMA-1: A multicenter study of KTE-C19 anti-CD19 CAR T cell therapy in refractory aggressive lymphoma. Mol Ther. 2017 Jan 4;25(1):285-295. Epub 2017 Jan 4. link to original article link to PMC article PubMed NCT02348216
   1. Update: Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang D, Wiezorek J, Go WY. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017 Dec 28;377(26):2531-2544. Epub 2017 Dec 10. link to original article contains dosing details in manuscript link to PMC article PubMed
   2. Update: Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO, Lin Y, Braunschweig I, Hill BT, Timmerman JM, Deol A, Reagan PM, Stiff P, Flinn IW, Farooq U, Goy A, McSweeney PA, Munoz J, Siddiqi T, Chavez JC, Herrera AF, Bartlett NL, Wiezorek JS, Navale L, Xue A, Jiang Y, Bot A, Rossi JM, Kim JJ, Go WY, Neelapu SS. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 2019 Jan;20(1):31-42. Epub 2018 Dec 2. link to original article link to PMC article contains dosing details in manuscript PubMed
2. ELIANA: Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, Bader P, Verneris MR, Stefanski HE, Myers GD, Qayed M, De Moerloose B, Hiramatsu H, Schlis K, Davis KL, Martin PL, Nemecek ER, Yanik GA, Peters C, Baruchel A, Boissel N, Mechinaud F, Balduzzi A, Krueger J, June CH, Levine BL, Wood P, Taran T, Leung M, Mueller KT, Zhang Y, Sen K, Lebwohl D, Pulsipher MA, Grupp SA. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018 Feb 1;378(5):439-448. link to original article link to supplementary protocol contains dosing details in supplement link to PMC article PubMed NCT02435849
3. JULIET: Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, Jäger U, Jaglowski S, Andreadis C, Westin JR, Fleury I, Bachanova V, Foley SR, Ho PJ, Mielke S, Magenau JM, Holte H, Pantano S, Pacaud LB, Awasthi R, Chu J, Anak Ö, Salles G, Maziarz RT; JULIET Investigators. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019 Jan 3;380(1):45-56. Epub 2018 Dec 1. link to original article PubMed NCT02445248
   1. Update: Schuster SJ, Tam CS, Borchmann P, Worel N, McGuirk JP, Holte H, Waller EK, Jaglowski S, Bishop MR, Damon LE, Foley SR, Westin JR, Fleury I, Ho PJ, Mielke S, Teshima T, Janakiram M, Hsu JM, Izutsu K, Kersten MJ, Ghosh M, Wagner-Johnston N, Kato K, Corradini P, Martinez-Prieto M, Han X, Tiwari R, Salles G, Maziarz RT. Long-term clinical outcomes of tisagenlecleucel in patients with relapsed or refractory aggressive B-cell lymphomas (JULIET): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2021 Oct;22(10):1403-1415. Epub 2021 Sep 10. link to original article PubMed