Autologous HSCT

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Aric C. Hall, MD
Madison, WI

Twitter: AricHall1

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.

26 regimens on this page
50 variants on this page

Contents


High dose therapy conditioning regimens, all lines of therapy

BCNU/TT

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BCNU/TT: BCNU (Carmustine), ThioTepa

Variant #1

Study Evidence
Illerhaus et al. 2006 Phase II

Chemotherapy

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

Variant #2

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

Chemotherapy

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

Variant #1

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

Chemotherapy

Variant #2

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

Chemotherapy

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)

Variant #3

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

Chemotherapy

Supportive medications

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 verified protocol 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 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. MCL1/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 verified protocol PubMed

BEAM

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

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

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

Chemotherapy

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

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

Chemotherapy

Variant #3, 300/100q12/200q12/140

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

Chemotherapy

Supportive medications

  • (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 BID on Monday and Thursdays, until 6 months after BEAM

While ANC less than 500/uL:

Stem cells re-infused on day 0

Variant #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

Variant #5, 300/150q12/200q12/140

Study Evidence Comparator Efficacy
Josting et al. 2005 Phase II
Schmitz et al. 2002 Phase III (E) DexaBEAM Seems to have superior FFTF

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

Chemotherapy

Stem cells re-infused on day 0

Variant #6, 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

Variant #7, 300/200/200/140

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

Chemotherapy

Variant #8, 300/200/200q12/140

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

Chemotherapy

Supportive medications

Variant #9, 300/200q12/200q12/140

Study Evidence
Zinzani et al. 2003 Retrospective

Chemotherapy

Variant #10, 300/200/400/140

Study Evidence
Jo et al. 2008 Retrospective

Chemotherapy

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"

References

  1. 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 verified protocol PubMed
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. MCL1/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 verified protocol PubMed
  10. 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 verified protocol PubMed
  11. CORAL: Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Brière J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. Epub 2010 Jul 26. Erratum in: J Clin Oncol. 2012 May 20;30(15):1896. link to original article contains verified protocol link to PMC article PubMed
  12. 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
  13. 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 verified protocol PubMed
  14. GELTAMO-2006: Pardal E, Coronado M, Martín A, Grande C, Marín-Niebla A, Panizo C, Bello JL, Conde E, Hernández MT, Arranz R, Bargay J, González-Barca E, Pérez-Ceballos E, Montes-Moreno S, Caballero MD. Intensification treatment based on early FDG-PET in patients with high-risk diffuse large B-cell lymphoma: a phase II GELTAMO trial. Br J Haematol. 2014 Nov;167(3):327-36. Epub 2014 Jul 28. link to original article contains verified protocol PubMed
  15. 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 verified protocol link to PMC article PubMed
  16. ORCHARRD: van Imhoff GW, McMillan A, Matasar MJ, Radford J, Ardeshna KM, Kuliczkowski K, Kim W, Hong X, Goerloev JS, Davies A, Barrigón MD, Ogura M, Leppä S, Fennessy M, Liao Q, van der Holt B, Lisby S, Hagenbeek A. Ofatumumab versus rituximab salvage chemoimmunotherapy in relapsed or refractory diffuse large B-cell lymphoma: the ORCHARRD study. J Clin Oncol. 2017 Feb 10;35(5):544-51. Epub 2016 Dec 28. link to original article link to data supplement verified protocol in supplement PubMed

BeEAM

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

Regimen

Study Evidence
Visani et al. 2011 Phase I/II

Chemotherapy

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

Bortezomib & Melphalan

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Bor-HDM: Bortezomib, High Dose Melphalan

Variant #1, HDM 140 mg/m2

Study Evidence
Sanchorawala et al. 2015 Phase II

Chemotherapy

Stem cells re-infused on day 0

Variant #2, HDM 200 mg/m2

Study Evidence
Roussel et al. 2009 Phase II
Sanchorawala et al. 2015 Phase II

Chemotherapy

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
  2. 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 verified protocol PubMed

Busulfan & Cyclophosphamide

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Variant #1, 16/120

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

Chemotherapy

Variant #2, 16/200

Study Evidence Comparator Efficacy
Ravindranath et al. 1996 Phase III (E) Intensive chemotherapy Seems not superior

Chemotherapy

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 verified protocol 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 (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

Busulfan & Melphalan

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Variant #1, PO busulfan (12 mg/kg)

Study Evidence
Yanada et al. 2013 Phase II

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

Chemotherapy

Stem cells re-infused on day 0

Variant #2, PO busulfan (16 mg/kg)

Study Evidence
Atra et al. 1997 Phase II, <20 pts

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

Chemotherapy

Stem cells re-infused on day 0

Variant #3, IV busulfan

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

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 verified protocol 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/TT

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Bu/TT: Busulfan, ThioTepa

Regimen

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

Chemotherapy

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 verified protocol PubMed

Bu/TT/Cy

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

Regimen

Study Evidence
Omuro et al. 2015 Phase II

Primary indication: primary CNS lymphoma (PCNSL)

Chemotherapy

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

CBV

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

Variant #1, 100/300/60, some BSA-based

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

Chemotherapy

Stem cells re-infused on day 0

Variant #2, 100/15/60, all weight-based

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

Chemotherapy

Supportive medications

Stem cells re-infused on day 0

Variant #3, 1500/300/250, all BSA-based

Study Evidence
Zinzani et al. 2003 Retrospective

Chemotherapy

Stem cells re-infused on day 0

Variant #4, 1800/600/400

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

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

Chemotherapy

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 verified protocol 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

CBV-Mx

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

Regimen

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

Chemotherapy

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 Study Group. 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 verified protocol 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

CTCb

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CTCb: Cyclophosphamide, Thiotepa, Carboplatin

Regimen

Study Evidence Comparator Efficacy
Eder et al. 1990 Phase I/II
Rodenhuis et al. 1998 Randomized Phase II (E) Standard adjuvant therapy Seems not superior
Stadtmauer et al. 2000 (Philadelphia Bone Marrow Transplant Group) Phase III (E) CMF Seems not superior
Rodenhuis et al. 2003 Phase III (E) FEC x 5 Might have superior RFS

No longer used, but of historical interest.

Chemotherapy

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. Philadelphia Bone Marrow Transplant Group: 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. 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

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

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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Cy/TBI: Cyclophosphamide & Total Body Irradiation

Regimen

Study Evidence Comparator Efficacy
Reimer et al. 2004 Phase II
Dreyling et al. 2004 Phase III (E) Interferon alfa maintenance Seems to have superior PFS

Chemoradiotherapy

References

  1. 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. 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 verified protocol PubMed
  2. 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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Etoposide & TBI: Etoposide & Total Body Irradiation

Regimen

Study Evidence Comparator Efficacy
Rowe et al. 2005 (MRC UKALL XII/ECOG E2993) Phase III (E) 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

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 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

FEAM

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

Regimen

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

Chemotherapy

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

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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

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 verified protocol in supplement PubMed

Melphalan & TBI

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Melphalan & TBI: Melphalan & Total Body Irradiation

Regimen

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

Chemoradiotherapy

References

  1. LM1996/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; 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

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

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.

Chemotherapy

Stem cells re-infused on day 0

Variant #2, 750/300/800/800/140

Study Evidence Comparator Efficacy
Vose et al. 2013 (BMT CTN 0401) Phase III (C) B-BEAM Seems not superior

Chemotherapy

Stem cells re-infused on day 0

Variant #3, 750/300/1600/3200/140

Study Evidence
Kirschey et al. 2014 Phase II

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

Chemotherapy

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 verified protocol PubMed
  2. 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
  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 Group. 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 verified protocol in supplement 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

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

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

TBI

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TBI: Total Body Irradiation

Regimen

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

Radiotherapy

References

  1. 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 verified protocol link to PMC article PubMed


Z-BEAM

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

Variant #1

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

Chemoradioimmunotherapy

Supportive medications

Stem cells re-infused on day 0

Variant #2

Study Evidence
Fruchart et al. 2014 Phase II

Chemoradioimmunotherapy

Supportive medications

  • "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. 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 regimens for cellular therapy, all lines of therapy

Bendamustine monotherapy

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Regimen

Study Evidence
Schuster et al. 2017 (JULIET) Phase II

Note: details in the abstract are scanty, and do not include the interval between conditioning and CAR-T infusion.

Chemotherapy

References

  1. Abstract: Schuster SJ, Bishop MR, Tam C, et al. Global Pivotal Phase 2 Trial of the CD19‐Targeted Therapy CTL019 in Adult Patients with Relapsed or Refractory (R/R) Diffuse Large B‐Cell Lymphoma (DLBCL)—an Interim Analysis. Hematological Oncology. 2017;35(S2):27. link to abstract

CYVE

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CYVE: CYclophosphamide & VEpeside (Etoposide)

Regimen

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

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

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 verified protocol in supplement PubMed

FC

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FC: Fludarabine & Cyclophosphamide

Variant #1, 250/25

Study Evidence
Schuster et al. 2017 (JULIET) Phase II

Note: details in the abstract are scanty, and do not include the interval between conditioning and CAR-T infusion.

Chemotherapy

Variant #2, 500/30, 2 doses of cyclophosphamide, 4 doses of fludarabine

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

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

Chemotherapy


Variant #3, 500/30, 3 doses of cyclophosphamide, 3 doses of fludarabine

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

Chemotherapy

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
  2. Abstract: Schuster SJ, Bishop MR, Tam C, et al. Global Pivotal Phase 2 Trial of the CD19‐Targeted Therapy CTL019 in Adult Patients with Relapsed or Refractory (R/R) Diffuse Large B‐Cell Lymphoma (DLBCL)—an Interim Analysis. Hematological Oncology. 2017;35(S2):27. link to abstract
  3. 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 verified protocol in supplement PubMed