Difference between revisions of "Autologous HSCT"
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''A minimum number of 2 × 10<sup>6</sup>/kg bw CD34-positive cells were required to proceed.'' | ''A minimum number of 2 × 10<sup>6</sup>/kg bw CD34-positive cells were required to proceed.'' | ||
+ | <section begin=77f5a0 /> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days -8 & -2 | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days -8 & -2 | ||
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*[[Cytarabine (Cytosar)]] 400 mg/m<sup>2</sup> IV BID on days -6 to -3 | *[[Cytarabine (Cytosar)]] 400 mg/m<sup>2</sup> IV BID on days -6 to -3 | ||
*[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once on day -2 | *[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once on day -2 | ||
− | + | <section end=77f5a0 /> | |
''Patients in the '''Lyma''' trial were then randomized to [[Mantle_cell_lymphoma#Rituximab_monotherapy|rituximab maintenance]] versus [[Mantle_cell_lymphoma#Observation_2|observation]].'' | ''Patients in the '''Lyma''' trial were then randomized to [[Mantle_cell_lymphoma#Rituximab_monotherapy|rituximab maintenance]] versus [[Mantle_cell_lymphoma#Observation_2|observation]].'' | ||
Revision as of 14:57, 11 October 2017
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Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are invited to contribute to the site.
Unlike the other chemotherapy regimen pages, this one is not disease-specific. Rather, this is a gathering point for all autologous hematopoietic stem cell transplant (HSCT) conditioning regimens. Unless otherwise specified, the day of hematopoietic stem cell reinfusion is by convention day 0.
26 regimens on this page
54 variants on this page
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Conditioning regimens
BCNU/TT
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BCNU/TT: BCNU (Carmustine), ThioTepa
Regimen #1
Study | Evidence |
Illerhaus et al. 2006 | Phase II |
Chemotherapy
- Carmustine (BiCNU) 400 mg/m2 IV once on day 50
- Thiotepa (Thioplex) 5 mg/kg (route not specified) once per day on days 51 & 52
Supportive medications
- Granulocyte colony-stimulating factor starting on day 61, continued until WBC greater than 1x109/L for 3 days
- "Standard supportive measures were taken according to institutional guidelines."
Stem cells re-infused on day 56
Regimen #2
Study | Evidence |
Illerhaus et al. 2008 | Pilot, <20 pts |
Chemotherapy
- Carmustine (BiCNU) 400 mg/m2 IV once on day 1
- Thiotepa (Thioplex) 5 mg/kg (route not specified) BID on days 2 & 3
Stem cells re-infused on day 7
References
- 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
- Illerhaus G, Müller F, Feuerhake F, Schäfer AO, Ostertag C, Finke J. High-dose chemotherapy and autologous stem-cell transplantation without consolidating radiotherapy as first-line treatment for primary lymphoma of the central nervous system. Haematologica. 2008 Jan;93(1):147-8. link to original article contains verified protocol PubMed
BEAC
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BEAC: BiCNU (Carmustine), Etoposide, Ara-C (Cytarabine), Cyclophosphamide
Regimen
Study | Evidence | Comparator | Efficacy |
Philip et al. 1995 (PARMA) | Phase III | DHAP x 4 | Seems to have superior OS |
Chemotherapy
- Carmustine (BiCNU) 300 mg/m2 IV once on day -7
- Etoposide (Vepesid) 800 mg/m2 IV once per day on days -6 to -3
- Cytarabine (Cytosar) 800 mg/m2 IV once per day on days -6 to -3
- Cyclophosphamide (Cytoxan) 35 mg/kg IV once per day on days -6 to -3
Supportive medications
- Filgrastim (Neupogen) 5 mcg/kg SC once per day starting on day +1, continued until there are 3 consecutive days with ANC greater than or equal to 1000/uL
- Prophylaxis against opportunistic infections and management of febrile neutropenia per "active protocols"
References
- Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med. 1995 Dec 7;333(23):1540-5. link to original article PubMed
- 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
BEAM
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BEAM: BiCNU (Carmustine), Etoposide, Ara-C (Cytarabine), Melphalan
Regimen #1
Study | Evidence | Comparator | Efficacy |
Shimoni et al. 2012 | Randomized Phase II | Z-BEAM | Seems to have inferior OS |
van Imhoff et al. 2016 (ORCHARRD) | Non-randomized portion of RCT |
Chemotherapy
- Carmustine (BiCNU) 300 mg/m2 IV once on day -6
- Etoposide (Vepesid) 200 mg/m2 IV once per day on days -5 to -2
- Cytarabine (Cytosar) 200 mg/m2 IV Q12H on days -5 to -2
- Melphalan (Alkeran) 140 mg/m2 IV once on day -1
Supportive medications
- Variously described
- Filgrastim (Neupogen) 5 mcg/kg SC once per day starting on day +4 "until engraftment"
- Valacyclovir (Valtrex) (dose not specified) for one month
- Trimethoprim/Sulfamethoxazole (Bactrim DS) (dose/frequency not specified) for six months
Regimen #2
Study | Evidence |
Alvarnas et al. 2016 (BMT CTN 0803/AMC 071) | Phase II |
Chemotherapy
- Carmustine (BiCNU) 300 mg/m2 IV once on day -6
- Etoposide (Vepesid) 100 mg/m2 IV Q12H on days -5 to -2 (8 total doses)
- Cytarabine (Cytosar) 100 mg/m2 IV Q12H on days -5 to -2 (8 total doses)
- Melphalan (Alkeran) 140 mg/m2 IV once on day -1
Regimen #3
Study | Evidence |
Gisselbrecht et al. 2010 (CORAL) | Non-randomized |
Chemotherapy
- Carmustine (BiCNU) 300 mg/m2 IV once on day -6
- Etoposide (Vepesid) 200 mg/m2 IV once per day on days -5 to -2
- Cytarabine (Cytosar) 200 mg/m2 IV once per day on days -5 to -2
- Melphalan (Alkeran) 140 mg/m2 IV once on day -1
Regimen #4
Study | Evidence |
Abrey et al. 2003 | Phase II |
Stewart et al. 2006 | Phase II |
Chemotherapy
- Carmustine (BiCNU) 300 mg/m2 IV once on day -6
- Etoposide (Vepesid) 100 mg/m2 IV Q12H on days -5 to -2 (8 total doses)
- Cytarabine (Cytosar) 200 mg/m2 IV Q12H on days -5 to -2 (8 total doses)
- Melphalan (Alkeran) 140 mg/m2 IV once on day -1
Supportive medications
- Patients less than 70 kg: Filgrastim (Neupogen) 300 mcg SC once per day starting on day +7 after stem cell transplant
- Patients greater than 70 kg (reference did not clarify which dosage to use for patients who are exactly 70 kg): Filgrastim (Neupogen) 480 mcg SC once per day starting on day +7 after stem cell transplant
- Trimethoprim/Sulfamethoxazole (Bactrim DS) (160/800 mg) PO BID on Monday and Thursdays, until 6 months after BEAM
While ANC less than 500:
- Ciprofloxacin (Cipro) 500 mg PO BID
- Fluconazole (Diflucan) 100 mg PO once per day or mycostatin 500,000 units swish & swallow QID
- Acyclovir (Zovirax) 400 mg PO TID
Regimen #5
Study | Evidence |
Colombat et al. 2006 | Phase II |
Chemotherapy
- Carmustine (BiCNU) 300 mg/m2 IV once on day 1
- Etoposide (Vepesid) 200 mg/m2 IV once per day on days 2 to 5
- Cytarabine (Cytosar) 100 mg/m2 IV Q12H on days 2 to 5
- Melphalan (Alkeran) 140 mg/m2 IV once on day 6
Day of transplant is not specified
Regimen #6
Study | Evidence |
Josting et al. 2005 | Phase II |
Paper did not specify which day peripheral blood stem cells were administered.
Chemotherapy
- Carmustine (BiCNU) 300 mg/m2 IV once on day 1
- Etoposide (Vepesid) 150 mg/m2 IV Q12H on days 2 to 5 (8 total doses)
- Cytarabine (Cytosar) 200 mg/m2 IV Q12H on days 2 to 5 (8 total doses)
- Melphalan (Alkeran) 140 mg/m2 IV once on day 1
Regimen #7
Study | Evidence |
Jo et al. 2008 | Retrospective |
Chemotherapy
- Carmustine (BiCNU) 300 mg/m2 IV once on day -6
- Etoposide (Vepesid) 200 mg/m2 IV once per day on days -5 to -2
- Cytarabine (Cytosar) 400 mg/m2 IV once per day on days -5 to -2
- Melphalan (Alkeran) 140 mg/m2 IV once on day -1
Supportive medications
- Filgrastim (Neupogen) 5 mcg/kg SC once per day starting on day +1, continued until there are 3 consecutive days with ANC =1000
- Prophylaxis against opportunistic infections and management of febrile neutropenia per "active protocols"
Regimen #8
Study | Evidence |
Zinzani et al. 2003 | Retrospective |
Chemotherapy
- Carmustine (BiCNU) 300 mg/m2 IV once on day -7
- Etoposide (Vepesid) 200 mg/m2 IV BID on days -6 to -3
- Cytarabine (Cytosar) 200 mg/m2 IV BID on days -6 to -3
- Melphalan (Alkeran) 140 mg/m2 IV once on day -2
References
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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 II |
To be completed
References
- Visani G, Malerba L, Stefani PM, Capria S, Galieni P, Gaudio F, Specchia G, Meloni G, Gherlinzoni F, Giardini C, Falcioni S, Cuberli F, Gobbi M, Sarina B, Santoro A, Ferrara F, Rocchi M, Ocio EM, Caballero MD, Isidori A. BeEAM (bendamustine, etoposide, cytarabine, melphalan) before autologous stem cell transplantation is safe and effective for resistant/relapsed lymphoma patients. Blood. 2011 Sep 22;118(12):3419-25. Epub 2011 Aug 3. link to original article PubMed
Bor-HDM
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Bor-HDM: Bortezomib, High Dose Melphalan
Regimen
Study | Evidence |
Roussel et al. 2009 | Phase II |
Autologous hematopoetic stem cell transplant on day 0.
Chemotherapy
- Bortezomib (Velcade) 1 mg/m2 IV once per day on days -6, -3, 1, 4
- Melphalan (Alkeran) 200 mg/m2 IV once on day -2
Supportive medications
- "All patients received standard supportive care measures"
References
- Roussel M, Moreau P, Huynh A, Mary JY, Danho C, Caillot D, Hulin C, Fruchart C, Marit G, Pégourié B, Lenain P, Araujo C, Kolb B, Randriamalala E, Royer B, Stoppa AM, Dib M, Dorvaux V, Garderet L, Mathiot C, Avet-Loiseau H, Harousseau JL, Attal M; Intergroupe Francophone du Myélome (IFM). Bortezomib and high-dose melphalan as conditioning regimen before autologous stem cell transplantation in patients with de novo multiple myeloma: a phase 2 study of the Intergroupe Francophone du Myelome (IFM). Blood. 2010 Jan 7;115(1):32-7. Epub 2009 Nov 2. link to original article contains verified protocol PubMed
Busulfan & Melphalan
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Regimen #1
Study | Evidence |
Yanada et al. 2013 | Phase II |
This regimen was evaluated in the setting of relapsed acute promyelocytic leukemia.
Chemotherapy
- Busulfan (Myleran) 1 mg/kg PO q6h on days -6 to -4
- Melphalan (Alkeran) 70 mg/m2 IV bolus once per day on days -3 & -2
Regimen #2
Study | Evidence |
Strauss et al. 2003 | Phase II |
This regimen was evaluated in the setting of metastatic Ewing's sarcoma. Note that melphalan is reported as given on day 2 (not day -2) in the original reference but this is surely an error.
Chemotherapy
- Busulfan (Myleran) 150 mg/m2 IV once per day on days -6 to -3
- Melphalan (Alkeran) 140 mg/m2 IV once on day -2
References
- Atra A, Whelan JS, Calvagna V, Shankar AG, Ashley S, Shepherd V, Souhami RL, Pinkerton CR. High-dose busulphan/melphalan with autologous stem cell rescue in Ewing's sarcoma. Bone Marrow Transplant. 1997 Nov;20(10):843-6. link to original article PubMed
- 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
- Yanada M, Tsuzuki M, Fujita H, Fujimaki K, Fujisawa S, Sunami K, Taniwaki M, Ohwada A, Tsuboi K, Maeda A, Takeshita A, Ohtake S, Miyazaki Y, Atsuta Y, Kobayashi Y, Naoe T, Emi N; Japan Adult Leukemia Study Group. Phase 2 study of arsenic trioxide followed by autologous hematopoietic cell transplantation for relapsed acute promyelocytic leukemia. Blood. 2013 Apr 18;121(16):3095-102. Epub 2013 Feb 14. link to original article contains verified protocol PubMed
Bu/Cy
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Regimen
Study | Evidence | Comparator | Efficacy |
Vellenga et al. 2011 (HOVON-SAKK AML-29/AML-42) | Phase III | Etoposide & Mitoxantrone | Might have superior RFS |
Treatment preceded by 7+3i, then amsacrine & cytarabine.
Chemotherapy
- Busulfan (Myleran) 4 mg/kg PO (frequency not specified) on days -7 to -4
- Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 & -2
References
- Vellenga E, van Putten W, Ossenkoppele GJ, Verdonck LF, Theobald M, Cornelissen JJ, Huijgens PC, Maertens J, Gratwohl A, Schaafsma R, Schanz U, Graux C, Schouten HC, Ferrant A, Bargetzi M, Fey MF, Löwenberg B; Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON).; Swiss Group for Clinical Cancer Research Collaborative Group (SAKK). Autologous peripheral blood stem cell transplantation for acute myeloid leukemia. Blood. 2011 Dec 1;118(23):6037-42. Epub 2011 Sep 27. link to original article contains verified protocol PubMed
Bu/TT
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Bu/TT: Busulfan, ThioTepa
Regimen
Study | Evidence |
Montemurro et al. 2007 (OSHO-53) | Phase II |
Chemotherapy
- Busulfan (Myleran) 4 mg/kg PO four times per day on days −8 to −5
- Thiotepa (Thioplex) 5 mg/kg IV once per day on days -4 & -3
References
- 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
C-VAMP, then Melphalan
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C-VAMP: Cyclophosphamide, Vincristine, Adriamycin (Doxorubicin), MethylPrednisolone
Regimen - multiple myeloma high-dose therapy
Study | Evidence | Comparator | Efficacy |
Child et al. 2003 (MRC Myeloma VII) | Phase III | ABCM | Seems to have superior OS |
C-VAMP portion
- Cyclophosphamide (Cytoxan) 500 mg IV once per day on days 1, 8, 15
- Cyclophosphamide was omitted in patients with a serum creatinine greater than 3.4 mg/dL
- Vincristine (Oncovin) 0.4 mg IV once per day on days 1 to 4 (total dose per cycle: 1.6 mg)
- Doxorubicin (Adriamycin) 9 mg/m2/day IV continuous infusion over 4 days (total dose per cycle: 36 mg/m2) on days 1 to 4
- Methylprednisolone (Solumedrol) 1000 mg/m2 (maximum dose per cycle of 1500 mg) PO/IV once per day on days 1 to 5
21-day cycles, given until maximal response was achieved. A minimum of 3 cycles given before stem cell harvest.
- Stem cell mobilization was performed with administration of Cyclophosphamide (Cytoxan) 2000 to 4000 mg/m2 IV with hydration and G-CSF on days 5 to 12
Chemotherapy
- Melphalan (Alkeran) 200 mg/m2 IV (no additional details given)
- Peripheral blood stem cells infused on day 0, 24 hours after melphalan
- Methylprednisolone (Solumedrol) 1500 mg IV once per day on days 0 to 3
An alternative to the above melphalan option was:
- Bone marrow autograft
- Total body irradiation (TBI)
- Melphalan (Alkeran) 140 mg/m2 IV (no additional details given)
- Methylprednisolone (Solumedrol) 1500 mg IV once per day on days 0 to 3
Interferon alfa maintenance therapy
- Interferon alfa-2a (Roferon-A) 3 million units SC three times per week
References
- Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Hawkins K, Brown J, Drayson MT, Selby PJ; Medical Research Council Adult Leukaemia Working Party. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med. 2003 May 8;348(19):1875-83. link to original article contains verified protocol PubMed
CBV
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CBV: Cyclophosphamide, BiCNU (Carmustine), VP-16 (Etoposide)
Regimen #1
Study | Evidence | Comparator | Efficacy |
Stiff et al. 2013 (SWOG S9704) | Phase III | R-CHOP x 8 | Superior PFS |
Chemotherapy
- Carmustine (BiCNU) 300 mg/m2 IV once on day -6
- Etoposide (Vepesid) 60 mg/kg (IBW) IV once on day -4
- Cyclophosphamide (Cytoxan) 100 mg/kg (IBW) IV once on day -2
Regimen #2
Study | Evidence |
Stiff et al. 1998 | Phase II |
Damon et al. 2009 (CALGB 59909) | Phase II |
Chemotherapy
- Carmustine (BiCNU) 15 mg/kg (maximum dose of 550 mg/m2) IV over 1 hour once on day -6
- Etoposide (Vepesid) 60 mg/kg IV over 4 hours once on day -4
- Cyclophosphamide (Cytoxan) 100 mg/kg IV over 2 hours once on day -2
Supportive medications
- Filgrastim (Neupogen) 5 mcg/kg SC once per day starting on day +4, to continue until ANC greater than 5000 once or greater than 1500 twice
- Levofloxacin (Levaquin) 500 mg PO once per day, starting on day +2, to continue until ANC ≥500
- Fluconazole (Diflucan) 200 mg PO once per day, starting on day +1, to continue until ANC ≥500
- Acyclovir (Zovirax) 200 mg PO TID, starting on day -2, to continue until 1 year after ASCT
- Trimethoprim/Sulfamethoxazole (Bactrim DS) 160/800 mg PO BID on Saturday and Sunday, to continue until 3 months after ASCT
Regimen #3, "CVB"
Study | Evidence |
Zinzani et al. 2003 | Retrospective |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1500 mg/m2 IV once per day on days -6 to -3
- Etoposide (Vepesid) 250 mg/m2 IV once per day on days -6 to -4
- Carmustine (BiCNU) 300 mg/m2 IV once on day -6
References
- Reece DE, Connors JM, Spinelli JJ, Barnett MJ, Fairey RN, Klingemann HG, Nantel SH, O'Reilly S, Shepherd JD, Sutherland HJ, et al. Intensive therapy with cyclophosphamide, carmustine, etoposide +/- cisplatin, and autologous bone marrow transplantation for Hodgkin's disease in first relapse after combination chemotherapy. Blood. 1994 Mar 1;83(5):1193-9. link to original article PubMed
- 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
- 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
- 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
- Stiff PJ, Unger JM, Cook JR, Constine LS, Couban S, Stewart DA, Shea TC, Porcu P, Winter JN, Kahl BS, Miller TP, Tubbs RR, Marcellus D, Friedberg JW, Barton KP, Mills GM, LeBlanc M, Rimsza LM, Forman SJ, Fisher RI. Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. N Engl J Med. 2013 Oct 31;369(18):1681-90. link to original article contains verified protocol link to PMC article PubMed
CTCb
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CTCb: Cyclophosphamide, Thiotepa, Carboplatin
Regimen
Study | Evidence | Comparator | Efficacy |
Eder et al. 1990 | Phase I/II | ||
Stadtmauer et al. 2000 (Philadelphia Bone Marrow Transplant Group) | Phase III | CMF | Seems not superior |
No longer used, but of historical interest.
Chemotherapy
References
- 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
- Stadtmauer EA, O'Neill A, Goldstein LJ, Crilley PA, Mangan KF, Ingle JN, Brodsky I, Martino S, Lazarus HM, Erban JK, Sickles C, Glick JH. Conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer. Philadelphia Bone Marrow Transplant Group. N Engl J Med. 2000 Apr 13;342(15):1069-76. link to original article PubMed
Cyclophosphamide, Etoposide, TBI
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Regimen
Study | Evidence |
Stiff et al. 1998 | Phase II |
Chemoradiotherapy
- Cyclophosphamide (Cytoxan) 100 mg/kg IV over 1 to 2 hours once on day -2
- Etoposide (Vepesid) 60 mg/kg IV over 4 hours once on day -4
- Total body irradiation (TBI) with 150 cGy fractions given twice per day (fractions are at least 5 hours apart) x 8 fractions (total dose: 1200 cGy) over 4 days on days -8 to -5, with lung shielding for the final 600 Gy
- Note: Table 1 of Stiff et al. 1998 lists the dosage of each fraction as being 120 cGy, in contrast to the body text under "treatment regimen" saying each fraction is 150 cGy. It is believed that the 150 cGy dose is correct since 8 fractions of this results in the correct total dose of 1200 cGy.
Supportive medications
- Diphenhydramine (Benadryl) 25 mg (route not specified) once 2 hours before Etoposide (Vepesid) to prevent allergic reaction
- Hydrocortisone (Cortef) 100 mg (route not specified) once 2 hours before Etoposide (Vepesid) to prevent allergic reaction
- "Continuous bladder irrigation and vigorous hydration were used" to protect against hemorrhagic cystitis
References
- 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
DHAP, then BEAC
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DHAP: Dexamethasone, High-dose Ara-C (Cytarabine), cisPlatin
BEAC: BiCNU, Etoposide, Ara-C (Cytarabine), Cyclophosphamide
Regimen
Study | Evidence |
Philip et al. 1991 (Parma) | Phase II |
DHAP Induction Therapy
In Velasquez, et al. 1988, Ara-C/Cytarabine was originally administered "on the third day," but the regimen was subsequently modified so that it was given on day 2 after cisplatin.
- Dexamethasone (Decadron) 40 mg PO/IV over 15 minutes once per day on days 1 to 4
- Cytarabine (Cytosar) 2000 mg/m2 IV over 3 hours on day 2, starting when cisplatin infusion is complete; a second dose of Cytarabine (Cytosar) 2000 mg/m2 IV over 3 hours is given after the first one
- Cisplatin (Platinol) 100 mg/m2 IV continuous infusion over 24 hours on day 1, starting after 6 hours of prehydration
Supportive medications
- Normal saline solution with mannitol, 50 g/L, at 250 mL/hour IV over 36 hours starting on day 1 prior to cisplatin
- Metoclopramide (Reglan) 1 mg/kg "given routinely as antiemetics"
- Diphenhydramine (Benadryl) 25 mg IV "given routinely as antiemetics"
21 to 28 day cycles, depending on degree of myelosuppression, for a total of 2 cycles as follows: After 1 course of DHAP, if they did not have "clearly progressive disease," patients underwent bone marrow harvest. A second course of DHAP was administered starting 1 day after bone marrow harvest. At day 20 after the second course of DHAP, patients were restaged. Patients who showed a response and had bulky disease at initial relapse then started involved field radiotherapy on day 20 after the second course of DHAP for 5 days per week x 2 weeks. In the original Velasquez, et al. 1988 paper where DHAP was used on its own, treatment continued for 6 to 10 cycles in patient who responded to treatment.
BEAC conditioning & transplant
BEAC starts on day 35 after the second course of DHAP. Autologous blood stem cells are infused on day 0.
- Carmustine (BiCNU) 300 mg/m2 IV over 30 minutes once on day -13
- Etoposide (Vepesid) 100 mg/m2 IV twice per day on days -12 to -7
- Cytarabine (Cytosar) 100 mg/m2 IV twice per day on days -12 to -9
- Cyclophosphamide (Cytoxan) 35 mg/kg IV over 60 minutes once per day on days -12 to -9
- Mesna (Mesnex) 50 mg/kg IV every day on days -12 to -9 (optional)
References
- DHAP portion: Velasquez WS, Cabanillas F, Salvador P, McLaughlin P, Fridrik M, Tucker S, Jagannath S, Hagemeister FB, Redman JR, Swan F, et al. Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP). Blood. 1988 Jan;71(1):117-22. link to original article contains verified protocol PubMed
- BEAC portion: Philip T, Chauvin F, Armitage J, Bron D, Hagenbeek A, Biron P, Spitzer G, Velasquez W, Weisenburger DD, Fernandez-Ranada J, et al. Parma international protocol: pilot study of DHAP followed by involved-field radiotherapy and BEAC with autologous bone marrow transplantation. Blood. 1991 Apr 1;77(7):1587-92. link to original article contains verified protocol PubMed
Etoposide & TBI
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Regimen
Study | Evidence | Comparator | Efficacy |
Rowe et al. 2005 (MRC UKALL XII/ECOG E2993) | Phase III | International ALL Trial consolidation and maintenance | Seems to have inferior OS |
Note: this is the same preparative regimen used for allogeneic transplant for certain patients; see reference for details. This regimen was evaluated in the treatment of acute lymphoblastic leukemia in CR1.
Radiotherapy
- TBI 220 cGy twice per day in 6 fractions on days –6 to –4 (total dose: 1320 cGy)
- Etoposide (Vepesid) 60 mg/kg IV once on day -3
References
- 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
- 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
- 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
- Update: Fielding AK, Rowe JM, Buck G, Foroni L, Gerrard G, Litzow MR, Lazarus H, Luger SM, Marks DI, McMillan AK, Moorman AV, Patel B, Paietta E, Tallman MS, Goldstone AH. UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. Blood. 2014 Feb 6;123(6):843-50. Epub 2013 Nov 25. link to original article contains verified protocol link to PMC article PubMed
LEED
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LEED: L-PAM (Melphalan), Endoxan (Cyclophosphamide), Etoposide, Dexamethasone
Regimen
Study | Evidence |
van Imhoff et al. 2016 (ORCHARRD) | Non-randomized portion of RCT |
Note: this protocol does not appear to be commonly used outside of Japan.
Chemotherapy
- Melphalan (Alkeran) 130 mg/m2 IV once on day -1
- Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -4 & -3
- Etoposide (Vepesid) 500 mg/m2 IV once per day on days -4 to -2
- Dexamethasone (Decadron) 40 mg IV once per day on days -4 to -1
References
- 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 monotherapy
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Regimen - immunoglobulin light-chain (AL) amyloidosis
Study | Evidence |
Skinner et al. 2004 | Phase II |
Eligibility criteria: Biopsy-proven amyloid disease and ≥1 major organ involved, evidence of plasma cell dyscrasia, no heart failure or arrhythmia that cannot be medically managed, cardiac ejection fraction ≥40%, no pleural effusions, supine systolic blood pressure ≥90 mmHg, O2 saturation ≥95% on room air, lung diffusing capacity ≥50% predicted, SWOG performance status ≤2 unless due to neuropathy.
Chemotherapy
- Patients who fulfilled all of these criteria--≤65 years old, cardiac ejection fraction ≥45%, and ≥2.5 x 106 CD34+ cells/kg collected--received Melphalan (Alkeran) 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 40-44%, or with 2.0-2.5 x 106 CD34+ cells/kg collected received Melphalan (Alkeran) 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
- 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
- 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
- Royer B, Minvielle S, Diouf M, Roussel M, Karlin L, Hulin C, Arnulf B, Macro M, Cailleres S, Brion A, Brechignac S, Belhadj K, Chretien ML, Wetterwald M, Chaleteix C, Tiab M, Leleu X, Frenzel L, Garderet L, Choquet S, Fuzibet JG, Dauriac C, Forneker LM, Benboubker L, Facon T, Moreau P, Avet-Loiseau H, Marolleau JP. Bortezomib, Doxorubicin, Cyclophosphamide, Dexamethasone Induction Followed by Stem Cell Transplantation for Primary Plasma Cell Leukemia: A Prospective Phase II Study of the Intergroupe Francophone du Myélome. J Clin Oncol. 2016 Jun 20;34(18):2125-32. Epub 2016 Apr 25. link to original article contains protocol PubMed
R-BEAM
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R-BEAM: Rituximab, BiCNU (Carmustine), Etoposide, Ara-C (Cytarabine), Melphalan
Regimen
Study | Evidence |
Kirschey et al. 2014 | Phase II |
A minimum number of 2 × 106/kg bw CD34-positive cells were required to proceed.
Chemotherapy
- Rituximab (Rituxan) 375 mg/m2 IV once per day on days -8 & -2
- Carmustine (BiCNU) 300 mg/m2 IV once on day -7
- Etoposide (Vepesid) 200 mg/m2 IV BID on days -6 to -3
- Cytarabine (Cytosar) 400 mg/m2 IV BID on days -6 to -3
- Melphalan (Alkeran) 140 mg/m2 IV once on day -2
Patients in the Lyma trial were then randomized to rituximab maintenance versus observation.
References
- 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
- Abstract: Steven Le Gouill, MD, PhD, Catherine Thieblemont, MD, PhD, Lucie Oberic, Krimo Bouabdallah, MD, Emmanuel Gyan, MD, PhD, Gandhi Damaj, MD, Vincent Ribrag, MD, Serge Bologna, MD, Remy Gressin, MD, Olivier Casasnovas, MD, Corinne Haioun, MD, PhD, Philippe Solal-Celigny, MD, Herve Maisonneuve, MD, Eric Van Den Neste, MD, PhD, Anne Moreau, MD, Marie C Bene, Gilles Salles, MD PhD, Hervé Tilly, MD, PhD, Thierry Lamy, MD, PhD and Olivier Hermine, MD, PhD. Rituximab Maintenance Versus Wait and Watch after Four Courses of R-DHAP Followed By Autologous Stem Cell transplantation in Previously Untreated Young Patients with Mantle Cell Lymphoma: First Interim Analysis of the Phase III Prospective Lyma Trial, a Lysa Study. ASH Annual Meeting 2014, Abstract 146 link to abstract
- Srour SA, Li S, Popat UR, Qazilbash MH, Lozano-Cerrada S, Maadani F, Alousi A,vKebriaei P, Anderlini P, Nieto Y, Jones R, Shpall E, Champlin RE, Hosing C. A randomized phase II study of standard-dose versus high-dose rituximab with BEAM in autologous stem cell transplantation for relapsed aggressive B-cell non-hodgkin lymphomas: long term results. Br J Haematol. 2017 Aug;178(4):561-570. Epub 2017 May 9. link to orignal article PubMed
R-TBI/Cy
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R-TBI/Cy: Rituximab, Total, Body, Irradiation, Cyclophosphamide
Regimen
Study | Evidence |
Kirschey et al. 2014 | Phase II |
A minimum number of 2 × 106/kg bw CD34-positive cells were required to proceed.
Chemoradiotherapy
- Rituximab (Rituxan) 375 mg/m2 IV once per day on days -8 & -2
- Total body irradiation (TBI) with a total dose of 12 Gy over 3 days (days -6 to -4) in fractions
- Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 & -2
References
- Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. link to original article contains verified protocol PubMed
TAM6
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TAM: Total-body irradiation, Ara-C (Cytarabine), Melphalan
Regimen
Study | Evidence |
Delarue et al. 2012 | Phase II |
Chemoradiotherapy
- Total body irradiation (TBI) with a total dose of 10 Gy over 3 days using twice per day fractions
- Cytarabine (Cytosar) 1500 mg/m2 IV Q12H x 2 days (total of 4 total doses)
- Melphalan (Alkeran) 140 mg/m2 IV
Supportive medications
"Antimicrobial prophylaxis and use of G-CSF or erythropoietin were permitted according to physician decision."
References
- Delarue R, Haioun C, Ribrag V, Brice P, Delmer A, Tilly H, Salles G, Van Hoof A, Casasnovas O, Brousse N, Lefrere F, Hermine O; for the Groupe d'Etude des Lymphomes de l'Adulte (GELA). CHOP and DHAP plus rituximab followed by autologous stem cell transplantation in mantle cell lymphoma: a phase 2 study from the Groupe d'Etude des Lymphomes de l'Adulte. Blood. 2013 Jan 3;121(1):48-53. Epub 2012 Jun 20. link to original article contains verified protocol PubMed
TBC
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TBC: Thiotepa, Busulfan, , Cyclophosphamide
Bu/TT/Cy: Busulfan, ThioTepa, Cyclophosphamide
Regimen
Study | Evidence |
Omuro et al. 2015 | Phase II |
Primary indication: primary CNS lymphoma (PCNSL)
Chemotherapy
- Thiotepa (Thioplex) 250 mg/m2 IV once per day on days −9, −8, and −7
- Busulfan (Myleran) 3.2 mg/kg IV once per day on days −6, −5, and −4
- Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days −3 and −2
References
- 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
- Retrospective: DeFilipp Z, Li S, El-Jawahri A, Armand P, Nayak L, Wang N, Batchelor TT, Chen YB. High-dose chemotherapy with thiotepa, busulfan, and cyclophosphamide and autologous stem cell transplantation for patients with primary central nervous system lymphoma in first complete remission. Cancer. 2017 Aug 15;123(16):3073-3079. Epub 2017 Apr 3. link to original article PubMed
TBI
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TBI: Total Body Irradiation
Regimen
Study | Evidence | Comparator | Efficacy |
Stiff et al. 2013 (SWOG S9704) | Phase III | R-CHOP x 8 | Superior PFS |
Radiotherapy
- TBI in 1.5-Gy fractions twice per day on days −8 through −5 (total dose: 12 Gy)
References
- Stiff PJ, Unger JM, Cook JR, Constine LS, Couban S, Stewart DA, Shea TC, Porcu P, Winter JN, Kahl BS, Miller TP, Tubbs RR, Marcellus D, Friedberg JW, Barton KP, Mills GM, LeBlanc M, Rimsza LM, Forman SJ, Fisher RI. Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. N Engl J Med. 2013 Oct 31;369(18):1681-90. link to original article contains verified protocol link to PMC article PubMed
V-BEAM
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V-BEAM: Velcade (Bortezomib), BiCNU (Carmustine), Etoposide, Ara-C (Cytarabine), Melphalan
Regimen
Study | Evidence |
William et al. 2014 | Phase II |
Full details not available in abstract; to be added later.
Chemotherapy
- Bortezomib (Velcade) on days -11, -8, -5, -2
- Carmustine (BiCNU)
- Etoposide (Vepesid)
- Cytarabine (Cytosar)
- Melphalan (Alkeran)
References
- 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
VMCP/BVAP, then Melphalan
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VMCP: Vincristine, Melphalan, Cyclophosphamide, Prednisone
BVAP: BiCNU (Carmustine), Vincristine, Adriamycin (Doxorubicin), Prednisone
Regimen
Study | Evidence | Comparator | Efficacy |
Attal et al. 1996 | Phase III | VMCP/BVAP alone | Seems to have superior OS |
VMCP portion
- Vincristine (Oncovin) 1 mg IV once on day 1
- Melphalan (Alkeran) 5 mg/m2 PO once per day on days 1 to 4
- Cyclophosphamide (Cytoxan) 110 mg/m2 PO once per day on days 1 to 4
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 4
21-day cycles x 2 to 3 cycles, given in an alternating fashion with BVAP
BVAP portion
- Vincristine (Oncovin) 1 mg IV once on day 1
- Carmustine (BiCNU) 30 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 30 mg/m2 IV once on day 1
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 4
21-day cycles x 2 to 3 cycles, given in an alternating fashion with VMCP
VMCP and BVAP are given in an alternating fashion x a total of 4 to 6 cycles; patients with a WHO performance status less than 3, creatinine less than 1.7 mg/dL (150 µmol/L), and bone marrow (collected after cycle 4) with greater than 200 million nucleated cells/kg would proceed to melphalan, total body irradiation (TBI), and transplant:
Chemoradiotherapy
- Melphalan (Alkeran) 140 mg/m2 IV (no other details given about its administration)
- Total body irradiation (TBI) with a total dose of 8 Gy given over 4 days in 4 fractions, without lung shielding
- Autologous hematopoietic stem cell transplant after melphalan and TBI
- Interferon alfa treatment started after transplant when ANC greater than 1500/mm3 and platelets greater than 75,000/mm3
References
- Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, Casassus P, Maisonneuve H, Facon T, Ifrah N, Payen C, Bataille R. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myélome. N Engl J Med. 1996 Jul 11;335(2):91-7. link to original article contains verified protocol PubMed
Z-BEAM
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Z-BEAM: Zevalin (Ibritumomab tiuxetan), BiCNU (Carmustine), Etoposide, Ara-C (Cytarabine), Melphalan
Regimen #1
Study | Evidence | Comparator | Efficacy |
Shimoni et al. 2012 | Randomized Phase II | BEAM | Seems to have superior OS |
Briones et al. 2013 | Phase II |
Patients in Shimoni et al. 2012 had primary induction failure or were chemosensitive to salvage therapy. Patients in Briones et al. 2013 had primary induction failure or were refractory to salvage therapy.
Chemoradioimmunotherapy
- Rituximab (Rituxan) 250 mg/m2 IV once on day -14
- Ibritumomab tiuxetan & Yttrium-90 (Zevalin) 0.4 mCi/kg (maximum dose of 32 mCi) IV once on day -14, given after Rituximab (Rituxan)
- Carmustine (BiCNU) 300 mg/m2 IV once on day -6
- Etoposide (Vepesid) 200 mg/m2 IV once per day on days -5 to -2
- Cytarabine (Cytosar) 200 mg/m2 IV Q12H on days -5 to -2
- Melphalan (Alkeran) 140 mg/m2 IV once on day -1
Supportive medications
- Filgrastim (Neupogen) 5 mcg/kg SC once per day starting on day +4 (Shimoni et al. 2012) or day +7 (Briones et al. 2013) until engraftment
- Valacyclovir (Valtrex) (dose not specified) for one month (Shimoni et al. 2012)
- Acyclovir (Zovirax) (dose not specified) for one month (Briones et al. 2013)
- Trimethoprim/Sulfamethoxazole (Bactrim DS) (dose/frequency not specified) for six months (3 months in Briones et al. 2013)
Regimen #2
Study | Evidence |
Fruchart et al. 2014 | Phase II |
This regimen is intended for upfront consolidation. Patients achieved at least a PR to R-ACVBP or R-CHOP.
Chemoradioimmunotherapy
- Rituximab (Rituxan) 250 mg/m2 IV once per day on days -21 & -14
- Ibritumomab tiuxetan & Yttrium-90 (Zevalin) 0.4 mCi/kg (maximum dose of 32 mCi) IV once on day -14, given after Rituximab (Rituxan)
- Dose reduced to 0.3 mCi/kg if platelet count was greater than 100k and less than 150k.
- Carmustine (BiCNU) 300 mg/m2 IV once on day -7
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days -6 to -3
- Cytarabine (Cytosar) 200 mg/m2 IV Q12H on days -6 to -3
- Melphalan (Alkeran) 140 mg/m2 IV once on day -2
Supportive medications
- "According to standard use"
References
- 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 SD article PubMed
- 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
- 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
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