Difference between revisions of "Transplant conditioning regimens"
m (Text replacement - "<span style="background:#EEEE00; padding:3px 6px 3px 6px; border-color:black; border-width:2px; border-style:solid;">Phase I/II</span>" to "style="background-color:#EEEE00"|Phase I/II") |
m (Text replacement - "<span style="background:#00CD00; padding:3px 6px 3px 6px; border-color:black; border-width:2px; border-style:solid;">Phase III</span>" to "style="background-color:#00CD00"|Phase III") |
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|[http://www.nejm.org/doi/full/10.1056/NEJM199512073332305 Philip et al. 1995 (PARMA)] | |[http://www.nejm.org/doi/full/10.1056/NEJM199512073332305 Philip et al. 1995 (PARMA)] | ||
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|[[Diffuse_large_B-cell_lymphoma#DHAP|DHAP x 4]] | |[[Diffuse_large_B-cell_lymphoma#DHAP|DHAP x 4]] | ||
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|[http://www.nejm.org/doi/full/10.1056/NEJMoa022340 Child et al. 2003 (MRC Myeloma VII)] | |[http://www.nejm.org/doi/full/10.1056/NEJMoa022340 Child et al. 2003 (MRC Myeloma VII)] | ||
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|ABCM | |ABCM | ||
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|[http://www.nejm.org/doi/full/10.1056/NEJM199607113350204 Attal et al. 1996] | |[http://www.nejm.org/doi/full/10.1056/NEJM199607113350204 Attal et al. 1996] | ||
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|VMCP/BVAP alone | |VMCP/BVAP alone | ||
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|[http://jco.ascopubs.org/content/31/6/701.full Lee et al. 2013] | |[http://jco.ascopubs.org/content/31/6/701.full Lee et al. 2013] | ||
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|[[#Busulfan_.26_Fludarabine_.28Flu.2FBu.3B_BuFlu.29|Busulfan & Fludarabine]] | |[[#Busulfan_.26_Fludarabine_.28Flu.2FBu.3B_BuFlu.29|Busulfan & Fludarabine]] | ||
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|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00200-4/abstract Rambaldi et al. 2015] | |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00200-4/abstract Rambaldi et al. 2015] | ||
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|[[#Busulfan_.26_Fludarabine_.28Flu.2FBu.3B_BuFlu.29|Busulfan & Fludarabine]] | |[[#Busulfan_.26_Fludarabine_.28Flu.2FBu.3B_BuFlu.29|Busulfan & Fludarabine]] | ||
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|[http://jco.ascopubs.org/content/31/6/701.full Lee et al. 2013] | |[http://jco.ascopubs.org/content/31/6/701.full Lee et al. 2013] | ||
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|[[#Busulfan_.26_Cyclophosphamide_.28BuCy.29|Busulfan & Cyclophosphamide]] | |[[#Busulfan_.26_Cyclophosphamide_.28BuCy.29|Busulfan & Cyclophosphamide]] | ||
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|[http://jco.ascopubs.org/content/28/17/2859.long Gyukocza et al. 2010] | |[http://jco.ascopubs.org/content/28/17/2859.long Gyukocza et al. 2010] | ||
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|[[Transplant_conditioning_regimens#Low-dose_TBI|Low-dose TBI]] | |[[Transplant_conditioning_regimens#Low-dose_TBI|Low-dose TBI]] | ||
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|[http://jco.ascopubs.org/content/28/17/2859.long Gyukocza et al. 2010] | |[http://jco.ascopubs.org/content/28/17/2859.long Gyukocza et al. 2010] | ||
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|[[Transplant_conditioning_regimens#Fludarabine_and_Low-dose_TBI|Fludarabine and Low-dose TBI]] | |[[Transplant_conditioning_regimens#Fludarabine_and_Low-dose_TBI|Fludarabine and Low-dose TBI]] | ||
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|[http://www.bloodjournal.org/content/early/2016/01/29/blood-2015-10-676924.long Richardson et al. 2016] | |[http://www.bloodjournal.org/content/early/2016/01/29/blood-2015-10-676924.long Richardson et al. 2016] | ||
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|"32 historical controls" | |"32 historical controls" | ||
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Revision as of 07:20, 25 October 2016
Use of this site is subject to you reading and agreeing with the terms set forth in the disclaimer.
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 transplant mobilization & conditioning regimens, the latter of which will eventually also be available under their respective disease-specific pages. However, this page will remain as a central reference for these types of regimens. Unless otherwise specified, the day of hematopoietic cell re-infusion is by convention day 0.
0 regimens on this page
0 variants on this page
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Stem cell mobilization
These are regimens intended to mobilize stem cells, very incomplete right now but will be filled in over time.
Cyclophosphamide & G-CSF
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Regimen
Study | Evidence |
Royer et al. 2016 | Phase II |
Mobilization regimen
- Cyclophosphamide (Cytoxan) 3000 mg/m2 IV once
- Filgrastim (Neupogen) 10 mcg/kg SC once per day and continued until ≥ 4 × 106/kg CD34+ cells are collected
References
- 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
Cytarabine & G-CSF
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Regimen
Study | Evidence |
Abrey et al. 2003 | Phase II |
Mobilization regimen
- Cytarabine (Cytosar) 3000 mg/m2 IV once per day on days 1 & 2
- Filgrastim (Neupogen) 10 mcg/kg SC once per day starting on day 4 and continued until stem cell collection complete
References
- 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
Cytarabine, Ifosfamide, G-CSF
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Regimen
Study | Evidence |
Colombat et al. 2006 | Phase II |
Mobilization regimen
- Cytarabine (Cytosar) 1000 mg/m2 IV Q12H on days 1 & 2
- Ifosfamide (Ifex) 1500 mg/m2 IV once per day on days 1 to 3
- Filgrastim (Neupogen) (dose/frequency not specified)
References
- 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
CYVE & G-CSF
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CYVE: CYtarabine, VEpesid (Etoposide)
Regimen
Study | Evidence |
Soussain et al. 2001 | Pilot, >20 pts |
Soussain et al. 2008 | Phase II |
Target collection dose not described; mobilization took place after the first course of CYVE salvage for CNS lymphoma.
Mobilization regimen
- Cytarabine (Cytosar) as follows:
- 2000 mg/m2 IV over 3 hours once per day on days 2 to 5
- 50 mg/m2 IV over 12 hours once per day on days 1 to 5
- Etoposide (Vepesid) 200 mg/m2 IV over 2 hours once per day on days 2 to 5
- Filgrastim (Neupogen) 5 μg/kg SC once per day starting 48 hours after end of chemotherapy
References
- Soussain C, Suzan F, Hoang-Xuan K, Cassoux N, Levy V, Azar N, Belanger C, Achour E, Ribrag V, Gerber S, Delattre JY, Leblond V. Results of intensive chemotherapy followed by hematopoietic stem-cell rescue in 22 patients with refractory or recurrent primary CNS lymphoma or intraocular lymphoma. J Clin Oncol. 2001 Feb 1;19(3):742-9. link to original article contains verified protocol PubMed
- Soussain C, Hoang-Xuan K, Taillandier L, Fourme E, Choquet S, Witz F, Casasnovas O, Dupriez B, Souleau B, Taksin AL, Gisselbrecht C, Jaccard A, Omuro A, Sanson M, Janvier M, Kolb B, Zini JM, Leblond V; Société Française de Greffe de Moëlle Osseuse-Thérapie Cellulaire. Intensive chemotherapy followed by hematopoietic stem-cell rescue for refractory and recurrent primary CNS and intraocular lymphoma: Société Française de Greffe de Moëlle Osseuse-Thérapie Cellulaire. J Clin Oncol. 2008 May 20;26(15):2512-8. Epub 2008 Apr 14. link to original article contains verified protocol PubMed
IGEV & Lenograstim
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IGEV: Ifosfamide, GEmcitabine, Vinorelbine
Regimen
Study | Evidence |
Magagnoli et al. 2007 | Phase II |
Mobilization regimen
- Ifosfamide (Ifex) 2000 mg/m2 IV over 2 hours once per day on days 1 to 4
- Gemcitabine (Gemzar) 800 mg/m2 IV once per day on days 1 & 4
- Vinorelbine (Navelbine) 20 mg/m2 IV once on day 1
- Prednisolone (Millipred) 100 mg PO once per day on days 1 to 4
Supportive medications
- Mesna (Mesnex) 900 mg/m2 IV at 0, 2, 4 hours after Ifosfamide (Ifex) on days 1 to 4
- Lenograstim (Granocyte) 263 µg SC once per day on days 7 until at least 3 x 106 CD34+ cells per kg of body weight were collected
Apheresis was performed when the peripheral blood CD34+ cell count exceeded 10 cells/µl.
References
- Magagnoli M, Spina M, Balzarotti M, Timofeeva I, Isa L, Michieli M, Capizzuto R, Morenghi E, Castagna L, Tirelli U, Santoro A. IGEV regimen and a fixed dose of lenograstim: an effective mobilization regimen in pretreated Hodgkin's lymphoma patients. Bone Marrow Transplant. 2007 Dec;40(11):1019-25. Epub 2007 Oct 1. link to original article contains verified protocol PubMed
Autologous stem cell transplant
BCNU/TT
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BCNU/TT: BCNU (Carmustine), ThioTepa
Regimen #1
Study | Evidence |
Illerhaus et al. 2006 | Phase II |
Preparative regimen
- 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 > 1x10^9/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 patients |
Preparative regimen
- 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 |
Philip et al. 1995 (PARMA) | Phase III | DHAP x 4 |
Treatment in PARMA preceded by DHAP x 2.
Preparative regimen
- 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 ≥1000
- 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 |
Shimoni et al. 2012 | Randomized Phase II | Z-BEAM |
Preparative regimen
- 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 "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 |
Preparative regimen
- 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 | Non-randomized |
Preparative regimen
- 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 |
Preparative regimen
- 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 <70 kg: Filgrastim (Neupogen) 300 mcg SC once per day starting on day +7 after stem cell transplant
- Patients >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 <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 |
Preparative regimen
- 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.
Preparative regimen
- 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 |
Preparative regimen
- 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 |
Preparative regimen
- 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 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 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.
Preparative regimen
- 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.
Preparative regimen
- 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.
Preparative regimen
- 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/TT
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Bu/TT: Busulfan, ThioTepa
Regimen
Study | Evidence |
Montemurro et al. 2007 (OSHO-53) | Phase II |
Preparative regimen
- 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
Bu/TT/Cy
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Bu/TT/Cy: Busulfan, ThioTepa, Cyclophosphamide
Regimen
Study | Evidence |
Omuro et al. 2015 | Phase II |
Preparative regimen
- Busulfan (Myleran) 3.2 mg/kg IV once per day on days −6, −5, and −4
- Thiotepa (Thioplex) 250 mg/m2 IV once per day on days −9, −8, and −7
- 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 PubMed
C-VAMP -> high-dose Melphalan (Alkeran)
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C-VAMP: Cyclophosphamide, Vincristine, Adriamycin (Doxorubicin), MethylPrednisolone
Regimen - multiple myeloma high-dose therapy
Study | Evidence | Comparator |
Child et al. 2003 (MRC Myeloma VII) | Phase III | ABCM |
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 >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
Preparative regimen
- 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 |
Stiff et al. 1998 | Phase II |
Damon et al. 2009 (CALGB 59909) | Phase II |
Preparative regimen
- 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 >5000 once or >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 #2, "CVB"
Study | Evidence |
Zinzani et al. 2003 | Retrospective |
Preparative regimen
- 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 PubMed
CTCb
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CTCb: Cyclophosphamide, Thiotepa, Carboplatin
Regimen
Study | Evidence | Comparator |
Eder et al. 1990 | Phase I/II | |
Stadtmauer et al. 2000 (Philadelphia Bone Marrow Transplant Group) | Phase III | CMF |
No longer used, but of historical interest.
Preparative regimen
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 |
Preparative regimen
- 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 -> 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 |
Rowe et al. 2005 (MRC UKALL XII/ECOG E2993) | Phase III | International ALL Trial consolidation and maintenance |
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.
Preparative regimen
- TBI 220 cGy twice daily 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 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 PubMed
High-dose Melphalan (Alkeran)
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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.
Preparative regimen
- 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.
Preparative regimen
- Rituximab (Rituxan) 375 mg/m2 IV once 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
Autologous blood stem cells are infused on day 0.
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
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.
Preparative regimen
- Rituximab (Rituxan) 375 mg/m2 IV once 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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Regimen
Study | Evidence |
Delarue et al. 2012 | Phase II |
Preparative regimen
- 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
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.
Preparative regimen
- 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 -> high-dose Melphalan (Alkeran)
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VMCP: Vincristine, Melphalan, Cyclophosphamide, Prednisone
BVAP: BiCNU (Carmustine), Vincristine, Adriamycin (Doxorubicin), Prednisone
Regimen
Study | Evidence | Comparator |
Attal et al. 1996 | Phase III | VMCP/BVAP alone |
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 <3, creatinine <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:
Preparative regimen
- 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 >1500/mm3 and platelets >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 |
Shimoni et al. 2012 | Randomized Phase II, >20 per arm | BEAM |
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.
Preparative regimen
- 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.
Preparative regimen
- 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 > 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 PubMed
- 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 SD article contains verified protocol PubMed
Allogeneic hematopoietic cell transplant, myeloablative
BEAM
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BEAM: BiCNU (Carmustine), Etoposide, Ara-C (Cytarabine), Melphalan
Regimen
Study | Evidence |
Przepiorka et al. 1999 | Phase II |
Sobol et al. 2013 | Phase II |
Preparative regimen
- Carmustine (BiCNU) 300 mg/m2 IV once on day -6
- Etoposide (Vepesid) 200 mg/m2 IV BID on days -5 to -2
- Cytarabine (Cytosar) 200 mg/m2 IV BID 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 +7 and continued until engraftment
- GVHD prophylaxis with Tacrolimus (Prograf) and Methotrexate (MTX)
- "Prophylactic antibiotics"
References
- Przepiorka D, van Besien K, Khouri I, Hagemeister F, Samuels B, Folloder J, Ueno NT, Molldrem J, Mehra R, Körbling M, Giralt S, Gajewski J, Donato M, Cleary K, Claxton D, Braunschweig I, Andersson B, Anderlini P, Champlin R. Carmustine, etoposide, cytarabine and melphalan as a preparative regimen for allogeneic transplantation for high-risk malignant lymphoma. Ann Oncol. 1999 May;10(5):527-32. link to original article contains protocol PubMed
- Sobol U, Rodriguez T, Smith S, Go A, Vimr R, Parthasarathy M, Guo R, Stiff P. Seven-year follow-up of allogeneic transplant using BCNU, etoposide, cytarabine and melphalan chemotherapy in patients with Hodgkin lymphoma after autograft failure: importance of minimal residual disease. Leuk Lymphoma. 2014 Jun;55(6):1281-7. Epub 2013 Oct 3. link to original article PubMed
BFR
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BFR: Bendamustine, Fludarabine, Rituximab
Regimen
Study | Evidence |
Khouri et al. 2014 | Phase II |
Preparative regimen
Note: the bendamustine infusion instructions are for the Treanda formulation, which was discontinued on 3/31/2016.
- Bendamustine 130 mg/m2 IV over 60 minutes once per day on days -5 to -3
- Fludarabine (Fludara) 30 mg/m2 IV over 30 minutes once per day on days -5 to -3
- Rituximab (Rituxan) (for "those with B-cell disease") 375 mg/m2 IV once on days -13, -6, +1, +8
GVHD prophylaxis
- See article for GVHD prophylaxis information
References
- Khouri IF, Wei W, Korbling M, Turturro F, Ahmed S, Alousi A, Anderlini P, Ciurea S, Jabbour E, Oran B, Popat UR, Rondon G, Bassett RL Jr, Gulbis A. BFR (bendamustine, fludarabine, and rituximab) allogeneic conditioning for chronic lymphocytic leukemia/lymphoma: reduced myelosuppression and GVHD. Blood. 2014 Oct 2;124(14):2306-12. Epub 2014 Aug 21. link to original article contains verified protocol PubMed
Busulfan & Cyclophosphamide (BuCy)
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Regimen
Study | Evidence | Comparator |
Lee et al. 2013 | Phase III | Busulfan & Fludarabine |
Rambaldi et al. 2015 | Phase III | Busulfan & Fludarabine |
Preparative regimen
- Busulfan (Myleran) 3.2 mg/kg IV once per day on days -7 to -4
- Cyclophosphamide (Cytoxan) 60 mg/kg IV once on days -3 and -2
Supportive medications
- "Cyclosporine alone or cyclosporine plus methotrexate according to the discretion of the attending physician"
- Filgrastim (Neupogen) 450 mcg SC once per day, starting on day +5 and continued until ANC >3,000
References
- Andersson BS, Kashyap A, Gian V, Wingard JR, Fernandez H, Cagnoni PJ, Jones RB, Tarantolo S, Hu WW, Blume KG, Forman SJ, Champlin RE. Conditioning therapy with intravenous busulfan and cyclophosphamide (IV BuCy2) for hematologic malignancies prior to allogeneic stem cell transplantation: a phase II study. Biol Blood Marrow Transplant. 2002;8(3):145-54. link to SD article PubMed
- Lee JH, Joo YD, Kim H, Ryoo HM, Kim MK, Lee GW, Lee JH, Lee WS, Park JH, Bae SH, Hyun MS, Kim DY, Kim SD, Min YJ, Lee KH. Randomized trial of myeloablative conditioning regimens: busulfan plus cyclophosphamide versus busulfan plus fludarabine. J Clin Oncol. 2013 Feb 20;31(6):701-9. Epub 2012 Nov 5. link to original article contains verified protocol PubMed
- Rambaldi A, Grassi A, Masciulli A, Boschini C, Micò MC, Busca A, Bruno B, Cavattoni I, Santarone S, Raimondi R, Montanari M, Milone G, Chiusolo P, Pastore D, Guidi S, Patriarca F, Risitano AM, Saporiti G, Pini M, Terruzzi E, Arcese W, Marotta G, Carella AM, Nagler A, Russo D, Corradini P, Alessandrino EP, Torelli GF, Scimè R, Mordini N, Oldani E, Marfisi RM, Bacigalupo A, Bosi A. Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2015 Nov;16(15):1525-36. Epub 2015 Sep 28. link to original article PubMed
Busulfan & Fludarabine (Flu/Bu; BuFlu)
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Regimen #1
Study | Evidence | Comparator |
Lee et al. 2013 | Phase III | Busulfan & Cyclophosphamide |
Preparative regimen
- Busulfan (Myleran) 3.2 mg/kg IV once per day on days -7 to -4
- Fludarabine (Fludara) 30 mg/m2 IV once per day on days -6 to -2
Supportive medications
- "Cyclosporine alone or with methotrexate according to the discretion of the attending physician"
- Filgrastim (Neupogen) 450 mcg SC once per day, starting on day +5 and continued until ANC >3,000
Regimen #2
Study | Evidence |
Russell et al. 2002 | Phase II |
Preparative regimen
- Fludarabine (Fludara) 50 mg/m2 IV once per day on days -6 to -2
- Busulfan (Myleran) 3.2 mg/kg (ideal body weight) IV once per day over 3 hours on days -5 to -2
Supportive medications
- Phenytoin (Dilantin) "loading" PO/IV, dosed to maintain therapeutic levels of 40 to 80 umol/L on days -5 to -2
- Ciprofloxacin (Cipro) 500 mg PO BID as prophylaxis
- Trimethoprim/Sulfamethoxazole (Bactrim DS) (dose not specified in reference, but assume 160/800 mg dose) PO 2 times a week as PCP prophylaxis
- No routine fungal prophylaxis
- No routine use of growth factors
- CMV negative blood
GVHD prophylaxis
- Antithymocyte globulin (Thymoglobulin, rabbit ATG) 0.5 mg/kg IV once on day -2; 2 mg/kg/day IV once on days -1 and 0 (total dose of 4.5 mg/kg)
- Cyclosporine modified (Neoral) or Cyclosporine non-modified (Sandimmune) PO/IV BID, with doses adjusted to maintain cyclosporine levels of 150 to 400 umol/L
- Methotrexate (MTX) 15 mg/m2 once on day 1; 10 mg/m2 once per day on days 3, 6, 11
- Folinic acid (Leucovorin) 5 mg started 24 hours after each dose of Methotrexate (MTX) and continued Q6H until 12 hours before the next dose of Methotrexate (MTX)
References
- Russell JA, Tran HT, Quinlan D, Chaudhry A, Duggan P, Brown C, Stewart D, Ruether JD, Morris D, Glick S, Gyonyor E, Andersson BS. Once-daily intravenous busulfan given with fludarabine as conditioning for allogeneic stem cell transplantation: study of pharmacokinetics and early clinical outcomes. Biol Blood Marrow Transplant. 2002;8(9):468-76. link to original article contains verified protocol PubMed
- Lee JH, Joo YD, Kim H, Ryoo HM, Kim MK, Lee GW, Lee JH, Lee WS, Park JH, Bae SH, Hyun MS, Kim DY, Kim SD, Min YJ, Lee KH. Randomized trial of myeloablative conditioning regimens: busulfan plus cyclophosphamide versus busulfan plus fludarabine. J Clin Oncol. 2013 Feb 20;31(6):701-9. Epub 2012 Nov 5. link to original article contains verified protocol PubMed
- Rambaldi A, Grassi A, Masciulli A, Boschini C, Micò MC, Busca A, Bruno B, Cavattoni I, Santarone S, Raimondi R, Montanari M, Milone G, Chiusolo P, Pastore D, Guidi S, Patriarca F, Risitano AM, Saporiti G, Pini M, Terruzzi E, Arcese W, Marotta G, Carella AM, Nagler A, Russo D, Corradini P, Alessandrino EP, Torelli GF, Scimè R, Mordini N, Oldani E, Marfisi RM, Bacigalupo A, Bosi A. Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2015 Nov;16(15):1525-36. Epub 2015 Sep 28. link to original article PubMed
Cyclophosphamide & TBI
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Regimen, Copelan et al. 2013
style="background-color:#ff0000"|Retrospective
This was a retrospective study from CIBMTR data; regimen and supportive medication details vary.
Preparative regimen
- Cyclophosphamide (Cytoxan)
- Total body irradiation (TBI)
References
- Retrospective: Copelan EA, Hamilton BK, Avalos B, Ahn KW, Bolwell BJ, Zhu X, Aljurf M, van Besien K, Bredeson C, Cahn JY, Costa LJ, de Lima M, Gale RP, Hale GA, Halter J, Hamadani M, Inamoto Y, Kamble RT, Litzow MR, Loren AW, Marks DI, Olavarria E, Roy V, Sabloff M, Savani BN, Seftel M, Schouten HC, Ustun C, Waller EK, Weisdorf DJ, Wirk B, Horowitz MM, Arora M, Szer J, Cortes J, Kalaycio ME, Maziarz RT, Saber W. Better leukemia-free and overall survival in AML in first remission following cyclophosphamide in combination with busulfan compared with TBI. Blood. 2013 Dec 5;122(24):3863-70. Epub 2013 Sep 24. link to original article PubMed
Etoposide & TBI
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Regimen #1
Study | Evidence |
Peters et al. 2015 (ALL-SCT-BFM 2003) | Non-randomized |
This regimen was evaluated in the treatment of high-risk pediatric acute lymphoblastic leukemia in CR1.
Preparative regimen
- TBI 200 cGy twice daily in 6 fractions on days -6 to -4 with lung shielding at 10 Gy (total dose: 1200 cGy)
- Etoposide (Vepesid) 60 mg/kg (maximum dose: 3600 mg) IV once on day -3
Regimen #2
Study | Evidence |
Rowe et al. 2005 (MRC UKALL XII/ECOG E2993) | Non-randomized |
Note: this is the same preparative regimen used for autologous transplant for certain patients; see reference for details. This regimen was evaluated in the treatment of acute lymphoblastic leukemia in CR1.
Preparative regimen
- TBI 220 cGy twice daily 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 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 PubMed
- Peters C, Schrappe M, von Stackelberg A, Schrauder A, Bader P, Ebell W, Lang P, Sykora KW, Schrum J, Kremens B, Ehlert K, Albert MH, Meisel R, Matthes-Martin S, Gungor T, Holter W, Strahm B, Gruhn B, Schulz A, Woessmann W, Poetschger U, Zimmermann M, Klingebiel T. Stem-cell transplantation in children with acute lymphoblastic leukemia: A prospective international multicenter trial comparing sibling donors with matched unrelated donors-The ALL-SCT-BFM-2003 trial. J Clin Oncol. 2015 Apr 10;33(11):1265-74. Epub 2015 Mar 9. link to original article PubMed
Fludarabine, Busulfan, Cyclophosphamide
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Regimen
Study | Evidence |
Glass et al. 2014 (DSHNHL R3) | Non-randomized |
This is described by the authors as a lymphoma-directed myeloablative conditioning regimen
Preparative regimen
- Fludarabine (Fludara) 25 mg/m2/day IV on days -8 to -4
- Busulfan (Myleran) 4 mg/kg/day PO or 3.2 mg/kg/day IV on days -6 to -4
- Cyclophosphamide (Cytoxan) 60 mg/kg/day IV on days -3 and -2
GVHD prophylaxis
- Tacrolimus (Prograf) 8 to 12 µg/L (route/frequency not specified) starting on day -1, tapered from day +100 in absence of GVHD
- Mycophenolate mofetil (CellCept) 1000 mg (route not specified) BID from day +1 to +28
- Antithymocyte globulin (Thymoglobulin, rabbit ATG) 2 mg/kg IV from day -3 to -1 (unclear if this is a total dose or a daily dose; option also to use ATG-Fresenius S at a higher dose of 10 mg/kg)
References
- Glass B, Hasenkamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M, Silling G, Wilhelm C, Zeis M, Görlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N; on behalf of the German High-Grade Lymphoma Study Group. Rituximab after lymphoma-directed conditioning and allogeneic stem-cell transplantation for relapsed and refractory aggressive non-Hodgkin lymphoma (DSHNHL R3): an open-label, randomised, phase 2 trial. Lancet Oncol. 2014 Jun;15(7):757-66. Epub 2014 May 11. link to original article link to original protocol (in German) contains verified protocol PubMed
Allogeneic hematopoietic cell transplant, reduced-intensity conditioning (RIC)
Busulfan & Fludarabine
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Regimen
Study | Evidence |
Devine et al. 2015 (CALGB 100103) | Phase II, <20 patients in this subgroup |
This regimen is meant for related donors; only 8 patients received this regimen before the addition of ATG (rabbit) after 2006.
Preparative regimen
- Fludarabine (Fludara) 30 mg/m2 IV over 30 minutes once per day on days -7 to -3
- Busulfan (Myleran) 0.8 mg/kg IV over 2 hours q6h on days -4 & -3 (8 total doses)
GVHD prophylaxis
- Tacrolimus (Prograf) with doses adjusted to maintain levels of 5 to 10 ng/mL, tapered on day +90 to off by day +180 (if no GVHD)
- Methotrexate (MTX) 5 mg/m2 IV once per day on days +1, +3, +6, +11
References
- Devine SM, Owzar K, Blum W, Mulkey F, Stone RM, Hsu JW, Champlin RE, Chen YB, Vij R, Slack J, Soiffer RJ, Larson RA, Shea TC, Hars V, Sibley AB, Giralt S, Carter S, Horowitz MM, Linker C, Alyea EP. Phase II Study of Allogeneic Transplantation for Older Patients With Acute Myeloid Leukemia in First Complete Remission Using a Reduced-Intensity Conditioning Regimen: Results From Cancer and Leukemia Group B 100103 (Alliance for Clinical Trials in Oncology)/Blood and Marrow Transplant Clinical Trial Network 0502. J Clin Oncol. 2015 Dec 10;33(35):4167-75. Epub 2015 Nov 2. link to original article contains verified protocol PubMed
Clofarabine & Melphalan
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Regimen
Study | Evidence |
Middeke et al. 2015 (BRIDGE) | Phase II |
Limited details are available in the abstract. Treatment is preceded by clofarabine & cytarabine salvage and is meant to be given during aplasia.
Preparative regimen
- Clofarabine (Clolar) 4 x 30 mg/m2 IV
- Melphalan (Alkeran) 140 mg/m2 IV
References
- Middeke JM, Herbst R, Parmentier S, Bug G, Hänel M, Stuhler G, Schäfer-Eckart K, Rösler W, Klein S, Bethge W, Bitz U, Büttner B, Knoth H, Alakel N, Schaich M, Morgner A, Kramer M, Sockel K, von Bonin M, Stölzel F, Platzbecker U, Röllig C, Thiede C, Ehninger G, Bornhäuser M, Schetelig J. Clofarabine salvage therapy before allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory AML: results of the BRIDGE trial. Leukemia. 2016 Feb;30(2):261-7. Epub 2015 Aug 18. link to original article contains protocol PubMed
Cyclophosphamide, Fludarabine, Thiotepa
Regimen
Details to be completed.
Preparative regimen
References
- Corradini P, Tarella C, Olivieri A, Gianni AM, Voena C, Zallio F, Ladetto M, Falda M, Lucesole M, Dodero A, Ciceri F, Benedetti F, Rambaldi A, Sajeva MR, Tresoldi M, Pileri A, Bordignon C, Bregni M. Reduced-intensity conditioning followed by allografting of hematopoietic cells can produce clinical and molecular remissions in patients with poor-risk hematologic malignancies. Blood. 2002 Jan 1;99(1):75-82. link to original article PubMed
FCR
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FCR: Fludarabine, Cyclophosphamide, Rituximab
Regimen
Study | Evidence |
Khouri et al. 2001 | Phase II |
Details are best described in Khouri et al. 2008.
Preparative regimen
- Fludarabine (Fludara) 30 mg/m2 IV once per day on days -5 to -3
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once per day on days -5 to -3
- Rituximab (Rituxan) as follows:
- 375 mg/m2 IV once on day -13
- 1000 mg/m2 IV once per day on days -6, +1, +8
GVHD prophylaxis
- Tacrolimus (Prograf) adjusted to level of 5 to 10 ng/mL for 6 months in patients in remission
- Methotrexate (MTX) as follows:
- Related donors: 5 mg/m2 IV once per day on days +1, +3, +6
- Unrelated donors: 5 mg/m2 IV once per day on days +1, +3, +6, +11
- Antithymocyte globulin, horse ATG (Atgam) as follows:
- Matched unrelated donor: 15 mg/kg IV once per day on days -5 to -3
References
- Khouri IF, Saliba RM, Giralt SA, Lee MS, Okoroji GJ, Hagemeister FB, Korbling M, Younes A, Ippoliti C, Gajewski JL, McLaughlin P, Anderlini P, Donato ML, Cabanillas FF, Champlin RE. Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality. Blood. 2001 Dec 15;98(13):3595-9. link to original article PubMed
- Update: Khouri IF, McLaughlin P, Saliba RM, Hosing C, Korbling M, Lee MS, Medeiros LJ, Fayad L, Samaniego F, Alousi A, Anderlini P, Couriel D, de Lima M, Giralt S, Neelapu SS, Ueno NT, Samuels BI, Hagemeister F, Kwak LW, Champlin RE. Eight-year experience with allogeneic stem cell transplantation for relapsed follicular lymphoma after nonmyeloablative conditioning with fludarabine, cyclophosphamide, and rituximab. Blood. 2008 Jun 15;111(12):5530-6. Epub 2008 Apr 14. Erratum in: Blood. 2009 Feb 12;113(7):1613. link to original article contains verified protocol PubMed
- Update: Khouri IF, Saliba RM, Erwin WD, Samuels BI, Korbling M, Medeiros LJ, Valverde R, Alousi AM, Anderlini P, Bashir Q, Ciurea S, Gulbis AM, de Lima M, Hosing C, Kebriaei P, Popat UR, Fowler N, Neelapu SS, Samaniego F, Champlin RE, Macapinlac HA. Nonmyeloablative allogeneic transplantation with or without 90yttrium ibritumomab tiuxetan is potentially curative for relapsed follicular lymphoma: 12-year results. Blood. 2012 Jun 28;119(26):6373-8. Epub 2012 May 14. link to original article contains verified protocol PubMed
Fludarabine and Low-dose TBI
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Regimen
Study | Evidence | Comparator |
Maris et al. 2003 | Phase II | |
Sorror et al. 2005 | Phase II | |
Gyukocza et al. 2010 | Phase III | Low-dose TBI |
Details are best described in Maris et al. 2003.
Preparative regimen
- Fludarabine (Fludara) 30 mg/m2 IV once per day on days -4 to -2
- Total body irradiation (TBI) 2 Gy at a rate of 0.07 Gy/min on day 0
GVHD prophylaxis
- Cyclosporine (type not specified) 6.25 mg/kg PO BID starting 4 to 6 hours after transplant, tapered at day 100 over 80 days (if no GVHD)
- Mycophenolate mofetil (CellCept) 15 mg/kg PO BID starting 4 to 6 hours after transplant, tapered at day 40 over 56 days (if no GVHD)
References
- Maris MB, Niederwieser D, Sandmaier BM, Storer B, Stuart M, Maloney D, Petersdorf E, McSweeney P, Pulsipher M, Woolfrey A, Chauncey T, Agura E, Heimfeld S, Slattery J, Hegenbart U, Anasetti C, Blume K, Storb R. HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies. Blood. 2003 Sep 15;102(6):2021-30. Epub 2003 Jun 5. link to original article contains verified protocol PubMed
- Sorror ML, Maris MB, Sandmaier BM, Storer BE, Stuart MJ, Hegenbart U, Agura E, Chauncey TR, Leis J, Pulsipher M, McSweeney P, Radich JP, Bredeson C, Bruno B, Langston A, Loken MR, Al-Ali H, Blume KG, Storb R, Maloney DG. Hematopoietic cell transplantation after nonmyeloablative conditioning for advanced chronic lymphocytic leukemia. J Clin Oncol. 2005 Jun 1;23(16):3819-29. Epub 2005 Apr 4. link to original article PubMed
- Update: Sorror ML, Storer BE, Sandmaier BM, Maris M, Shizuru J, Maziarz R, Agura E, Chauncey TR, Pulsipher MA, McSweeney PA, Wade JC, Bruno B, Langston A, Radich J, Niederwieser D, Blume KG, Storb R, Maloney DG. Five-year follow-up of patients with advanced chronic lymphocytic leukemia treated with allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. J Clin Oncol. 2008 Oct 20;26(30):4912-20. Epub 2008 Sep 15. link to original article PubMed
- Gyurkocza B, Storb R, Storer BE, Chauncey TR, Lange T, Shizuru JA, Langston AA, Pulsipher MA, Bredeson CN, Maziarz RT, Bruno B, Petersen FB, Maris MB, Agura E, Yeager A, Bethge W, Sahebi F, Appelbaum FR, Maloney DG, Sandmaier BM. Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. J Clin Oncol. 2010 Jun 10;28(17):2859-67. Epub 2010 May 3. link to original article contains verified protocol PubMed
- Björkstrand B, Iacobelli S, Hegenbart U, Gruber A, Greinix H, Volin L, Narni F, Musto P, Beksac M, Bosi A, Milone G, Corradini P, Goldschmidt H, de Witte T, Morris C, Niederwieser D, Gahrton G. Tandem autologous/reduced-intensity conditioning allogeneic stem-cell transplantation versus autologous transplantation in myeloma: long-term follow-up. J Clin Oncol. 2011 Aug 1;29(22):3016-22. Epub 2011 Jul 5. Erratum in: J Clin Oncol. 2011 Sep 20;29(27):3721. link to original article PubMed
- Update: Gahrton G, Iacobelli S, Björkstrand B, Hegenbart U, Gruber A, Greinix H, Volin L, Narni F, Carella AM, Beksac M, Bosi A, Milone G, Corradini P, Schönland S, Friberg K, van Biezen A, Goldschmidt H, de Witte T, Morris C, Niederwieser D, Garderet L, Kröger N; EBMT Chronic Malignancies Working Party Plasma Cell Disorders Subcommittee. Autologous/reduced-intensity allogeneic stem cell transplantation vs autologous transplantation in multiple myeloma: long-term results of the EBMT-NMAM2000 study. Blood. 2013 Jun 20;121(25):5055-63. Epub 2013 Mar 12. link to original article PubMed
Fludarabine, Busulfan, ATG
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Regimen #1
Study | Evidence |
Devine et al. 2015 (CALGB 100103) | Phase II |
This regimen is meant for all types of donors.
Preparative regimen
- Fludarabine (Fludara) 30 mg/m2 IV over 30 minutes once per day on days -7 to -3
- Busulfan (Myleran) 0.8 mg/kg IV over 2 hours q6h on days -4 & -3 (8 total doses)
- ATG (Rabbit) 2.5 mg/kg IV over 6 hours once per day on days -4 to -2
GVHD prophylaxis
- Tacrolimus (Prograf) with doses adjusted to maintain levels of 5 to 10 ng/mL, tapered on day +90 to off by day +180 (if no GVHD)
- Methotrexate (MTX) 5 mg/m2 IV once per day on days +1, +3, +6, +11
Regimen #2
Study | Evidence |
Mohti et al. 2014 | Phase II |
Preparative regimen
- Fludarabine (Fludara) 30 mg/m2/day (route not specified) on days -6 to -2 (5 consecutive days)
- Busulfan (Myleran) 130 mg/m2 IV over 3 hours once per day on days -5 to -3 (3 consecutive days)
- Antithymocyte globulin (ATG) (subtype not specified) 2.5 mg/kg/day IV on days -2 & -1
Supportive care as per Mohty et al. 2003.
Regimen #3
Study | Evidence |
Garban et al. 2006 (IFM99-04) | Non-randomized |
This regimen was meant for patients who had an HLA-identical sibling donor, and was evaluated in multiple myeloma patients.
Preparative regimen
- Fludarabine (Fludara) 25 mg/m2/day (route not specified) for 5 days (days not specified)
- Busulfan (Myleran) 2 mg/kg2 PO once per day for 2 days (days not specified)
- ATG, rabbit (Imtix) 2.5 mg/kg IV over 12 hours once per day on days -5 to -1 (5 doses)
GVHD prophylaxis
- Cylosporine (type not specified) with starting dose on day -1 of 3 mg/kg/day, doses adjusted to "serum levels", tapered on day +60 to off by day +100 (if no GVHD)
- Methotrexate (MTX) 10 mg/m2 (route not specified) once per day on days +1, +3, +6
Regimen #4
Study | Evidence |
Slavin et al. 1998 | Phase II |
Preparative regimen
- Fludarabine (Fludara) 30 mg/m2 IV once per day on days -10 to -5 (6 consecutive days)
- Busulfan (Myleran) 4 mg/kg/day PO on days -6 to -5 (2 consecutive days)
- ATG-Fresenius 10 mg/kg/day on days -4 to -1 (4 consecutive days)
References
- Slavin S, Nagler A, Naparstek E, Kapelushnik Y, Aker M, Cividalli G, Varadi G, Kirschbaum M, Ackerstein A, Samuel S, Amar A, Brautbar C, Ben-Tal O, Eldor A, Or R. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood. 1998 Feb 1;91(3):756-63. link to original article contains verified protocol PubMed
- Garban F, Attal M, Michallet M, Hulin C, Bourhis JH, Yakoub-Agha I, Lamy T, Marit G, Maloisel F, Berthou C, Dib M, Caillot D, Deprijck B, Ketterer N, Harousseau JL, Sotto JJ, Moreau P. Prospective comparison of autologous stem cell transplantation followed by dose-reduced allograft (IFM99-03 trial) with tandem autologous stem cell transplantation (IFM99-04 trial) in high-risk de novo multiple myeloma. Blood. 2006 May 1;107(9):3474-80. Epub 2006 Jan 5. link to original article contains verified protocol PubMed
- Update: Moreau P, Garban F, Attal M, Michallet M, Marit G, Hulin C, Benboubker L, Doyen C, Mohty M, Yakoub-Agha I, Leyvraz S, Casassus P, Avet-Loiseau H, Garderet L, Mathiot C, Harousseau JL; IFM Group. Long-term follow-up results of IFM99-03 and IFM99-04 trials comparing nonmyeloablative allotransplantation with autologous transplantation in high-risk de novo multiple myeloma. Blood. 2008 Nov 1;112(9):3914-5. link to original article PubMed
- Mohty M, Malard F, Blaise D, Milpied N, Furst S, Tabrizi R, Guillaume T, Vigouroux S, El-Cheikh J, Delaunay J, Le Gouill S, Moreau P, Labopin M, Chevallier P. Reduced-toxicity conditioning with fludarabine, once-daily intravenous busulfan, and antithymocyte globulins prior to allogeneic stem cell transplantation: results of a multicenter prospective phase 2 trial. Cancer. 2015 Feb 15;121(4):562-9. Epub 2014 Oct 3. Erratum in: Cancer. 2015 Mar 1;121(5):800. link to original article contains verified protocol PubMed
- Devine SM, Owzar K, Blum W, Mulkey F, Stone RM, Hsu JW, Champlin RE, Chen YB, Vij R, Slack J, Soiffer RJ, Larson RA, Shea TC, Hars V, Sibley AB, Giralt S, Carter S, Horowitz MM, Linker C, Alyea EP. Phase II Study of Allogeneic Transplantation for Older Patients With Acute Myeloid Leukemia in First Complete Remission Using a Reduced-Intensity Conditioning Regimen: Results From Cancer and Leukemia Group B 100103 (Alliance for Clinical Trials in Oncology)/Blood and Marrow Transplant Clinical Trial Network 0502. J Clin Oncol. 2015 Dec 10;33(35):4167-75. Epub 2015 Nov 2. link to original article contains verified protocol PubMed
Fludarabine, Busulfan, ATG, Ibritumomab tiuxetan
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Regimen
Study | Evidence |
Bouabdallah et al. 2015 | Phase II |
Preparative regimen
- Fludarabine (Fludara) 30 mg/m2 IV once per day on days -6 to -2
- Busulfan (Myleran) 3.2 mg/kg/day (route not specified) on days -5 & -4
- Antithymocyte globulin, rabbit ATG (Thymoglobulin) 2.5 mg/kg IV once on day -1
- Rituximab (Rituxan) 250 mg/m2 IV once per day on days -21 & -14
- Ibritumomab tiuxetan (Zevalin) 0.4 mCi/kg (maximum dose of 32 mCi) IV once on day -14
GVHD prophylaxis
- Cyclosporine (type and dose not specified) until day +90 and tapered off by day +180 based on chimerism and GVHD
- Methotrexate (MTX) as follows (for unrelated donors with HLA mismatch):
- 15 mg/m2 (route not specified) once on day +1
- 10 mg/m2 (route not specified) once per day on days +3 & +6
References
- Bouabdallah K, Furst S, Asselineau J, Chevalier P, Tournilhac O, Ceballos P, Vigouroux S, Tabrizi R, Doussau A, Bouabdallah R, Mohty M, Le Gouill S, Blaise D, Milpied N. 90Y-ibritumomab tiuxetan, fludarabine, busulfan and antithymocyte globulin reduced-intensity allogeneic transplant conditioning for patients with advanced and high-risk B-cell lymphomas. Ann Oncol. 2015 Jan;26(1):193-8. Epub 2014 Oct 30. link to original article contains verified protocol PubMed
Fludarabine & Cyclophosphamide
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Regimen
Study | Evidence |
Dreger et al. 2010 (CLL3X) | Phase II |
This regimen is intended for related donors.
Preparative regimen
- Fludarabine (Fludara) 30 mg/m2 IV once per day on days -6 to -2
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once per day on days -6 to -2
References
- Dreger P, Döhner H, Ritgen M, Böttcher S, Busch R, Dietrich S, Bunjes D, Cohen S, Schubert J, Hegenbart U, Beelen D, Zeis M, Stadler M, Hasenkamp J, Uharek L, Scheid C, Humpe A, Zenz T, Winkler D, Hallek M, Kneba M, Schmitz N, Stilgenbauer S; German CLL Study Group. Allogeneic stem cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia: long-term clinical and MRD results of the German CLL Study Group CLL3X trial. Blood. 2010 Oct 7;116(14):2438-47. Epub 2010 Jul 1. link to original article contains verified protocol PubMed
- Update: Dreger P, Schnaiter A, Zenz T, Böttcher S, Rossi M, Paschka P, Bühler A, Dietrich S, Busch R, Ritgen M, Bunjes D, Zeis M, Stadler M, Uharek L, Scheid C, Hegenbart U, Hallek M, Kneba M, Schmitz N, Döhner H, Stilgenbauer S. TP53, SF3B1, and NOTCH1 mutations and outcome of allotransplantation for chronic lymphocytic leukemia: six-year follow-up of the GCLLSG CLL3X trial. Blood. 2013 Apr 18;121(16):3284-8. Epub 2013 Feb 22. link to original article PubMed
Fludarabine, Cyclophosphamide, ATG
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Regimen
Study | Evidence |
Dreger et al. 2010 (CLL3X) | Phase II |
This regimen is intended for unrelated donors.
Preparative regimen
- Fludarabine (Fludara) 30 mg/m2 IV once per day on days -6 to -2 (5 consecutive days)
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once per day on days -6 to -2 (5 consecutive days)
- ATG-Fresenius 10 mg/kg/day on days -4 to -1 (4 consecutive days)
References
- Dreger P, Döhner H, Ritgen M, Böttcher S, Busch R, Dietrich S, Bunjes D, Cohen S, Schubert J, Hegenbart U, Beelen D, Zeis M, Stadler M, Hasenkamp J, Uharek L, Scheid C, Humpe A, Zenz T, Winkler D, Hallek M, Kneba M, Schmitz N, Stilgenbauer S; German CLL Study Group. Allogeneic stem cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia: long-term clinical and MRD results of the German CLL Study Group CLL3X trial. Blood. 2010 Oct 7;116(14):2438-47. Epub 2010 Jul 1. link to original article contains verified protocol PubMed
- Update: Dreger P, Schnaiter A, Zenz T, Böttcher S, Rossi M, Paschka P, Bühler A, Dietrich S, Busch R, Ritgen M, Bunjes D, Zeis M, Stadler M, Uharek L, Scheid C, Hegenbart U, Hallek M, Kneba M, Schmitz N, Döhner H, Stilgenbauer S. TP53, SF3B1, and NOTCH1 mutations and outcome of allotransplantation for chronic lymphocytic leukemia: six-year follow-up of the GCLLSG CLL3X trial. Blood. 2013 Apr 18;121(16):3284-8. Epub 2013 Feb 22. link to original article PubMed
Fludarabine, Cyclophosphamide, TBI for dUCB or haploidentical transplant
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dUCB: double Umbilical Cord Blood
Regimen #1, dUCB transplantation
Study | Evidence |
Brunstein et al. 2011 | Phase II |
Preparative regimen
- Fludarabine (Fludara) 40 mg/m2 IV once per day on days -6 to -2 (5 consecutive days)
- Cyclophosphamide (Cytoxan) 50 mg/kg IV once on day -6
- Total body irradiation (TBI) 2 Gy once on day -1
Supportive medications
- Mesna (Mesnex) (dose/route/schedule not specified) and "vigorous IV hydration for uroprotection."
- Filgrastim (Neupogen) 5 µg/kg SC once per day, starting on day +1, continued until ANC =2000/µL for 3 consecutive days
GVHD Prophylaxis
- Mycophenolate mofetil (CellCept) 1000 mg (route not specified) Q8H for patients >50 kg, starting on day -3 "and continuing until day +30 or 7 days after engraftment, whichever was later"
- Patients <50 kg received Mycophenolate mofetil (CellCept) 15 mg/kg (route not specified) Q8H, starting on day -3 "and continuing until day +30 or 7 days after engraftment, whichever was later"
- Cyclosporine A (Neoral vs. Sandimmune not specified, route not specified) with a goal trough of 200 to 400 ng/mL (starting date not specified) until day +100. Patients without GVHD had their dose tapered by 10% each week starting on day +101, with discontinuation of cyclosporine A around day +180 to +200.
- Tacrolimus (Prograf) (route not specified) with a goal trough level of 5 to 10 ng/mL could be substituted for cyclosporine.
Regimen #2, Haploidentical
Study | Evidence |
Brunstein et al. 2011 | Phase II |
Preparative regimen
- Fludarabine (Fludara) 30 mg/m2 IV once per day on days -6 to -2 (5 consecutive days)
- Cyclophosphamide (Cytoxan) 14.5 mg/kg IV once on days -6 and -5 (2 consecutive days)
- Total body irradiation (TBI) 2 Gy once on day -1
Supportive medications
- Mesna (Mesnex) (dose/route/schedule not specified) and "vigorous IV hydration for uroprotection."
- Filgrastim (Neupogen) 5 µg/kg SC once per day, starting on day +5, continued until ANC =1000/µL for 3 consecutive days
GVHD Prophylaxis
- Cyclophosphamide (Cytoxan) 50 mg/kg IBW IV over 1 to 2 hours once per day on days +3 (60 to 72 hours after marrow infusion) and +4
- Mycophenolate mofetil (CellCept) 15 mg/kg (maximum daily dose of 3000 mg; route not specified) Q8H, starting on day +5, continued until day +35 or longer at physician discretion if active GVHD was present
- Tacrolimus (Prograf) (route not specified) with a goal trough level of 5 to 10 ng/mL, starting on day +5, continued until day +180
References
- Brunstein CG, Fuchs EJ, Carter SL, Karanes C, Costa LJ, Wu J, Devine SM, Wingard JR, Aljitawi OS, Cutler CS, Jagasia MH, Ballen KK, Eapen M, O'Donnell PV;Blood and Marrow Transplant Clinical Trials Network. Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts. Blood. 2011 Jul 14;118(2):282-8. link to original article contains verified protocol PubMed
Fludarabine & Melphalan
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Regimen #1
Study | Evidence |
Sureda et al. 2011 | Phase II |
Preparative regimen
- Fludarabine (Fludara) 150 mg/m2 IV once per day on days -8 to -4
- Melphalan (Alkeran) 140 mg/m2 IV once per day on days -3 & -2
Recipients of stem cells from matched unrelated donors also received:
- Antithymocyte globulin (ATG) 45 mg/kg IV once per day on days -4 to -2
GVHD prophylaxis
- Cyclosporine A (not specified whether modified or non-modified) starting at 1.5 mg/kg BID IV on day -2
- Methotrexate (MTX) 10 mg/m2 IV once per day on days +1, +3, +6 and +11
If no acute GVHD of grade 2 or more, cyclosporine A is tapered down by 10% per week starting on day +90 with planned discontinuation by day +180.
Regimen #2
Study | Evidence |
Anderlini et al. 2008 | Phase II |
Preparative regimen
- Fludarabine (Fludara) 33 mg/m2 IV once per day on days -5 to -2
- Melphalan (Alkeran) 70 mg/m2 IV once per day on days -3 & -2
Recipients of stem cells from matched unrelated donors also received:
- Antithymocyte globulin (ATG) 2 mg/kg IV once per day on days -4 to -2
GVHD prophylaxis
- Tacrolimus (Prograf) IV starting on day -2, dosed to achieve serum levels 4–12 ng/mL and switched to PO as soon as possible. Continued for at least 6 months and then "tapered off" (instructions not given).
- Methotrexate (MTX) 5 mg/m2 IV once per day on days +1, +3, +6 (extra dose on day +11 for MUD recipients)
References
- Alvarez I, Sureda A, Caballero MD, Urbano-Ispizua A, Ribera JM, Canales M, García-Conde J, Sanz G, Arranz R, Bernal MT, de la Serna J, Díez JL, Moraleda JM, Rubió-Félix D, Xicoy B, Martínez C, Mateos MV, Sierra J. Nonmyeloablative stem cell transplantation is an effective therapy for refractory or relapsed hodgkin lymphoma: results of a spanish prospective cooperative protocol. Biol Blood Marrow Transplant. 2006 Feb;12(2):172-83. link to original article contains protocol PubMed
- Anderlini P, Saliba R, Acholonu S, Giralt SA, Andersson B, Ueno NT, Hosing C, Khouri IF, Couriel D, de Lima M, Qazilbash MH, Pro B, Romaguera J, Fayad L, Hagemeister F, Younes A, Munsell MF, Champlin RE. Fludarabine-melphalan as a preparative regimen for reduced-intensity conditioning allogeneic stem cell transplantation in relapsed and refractory Hodgkin's lymphoma: the updated M.D. Anderson Cancer Center experience. Haematologica. 2008 Feb;93(2):257-64. Epub 2008 Jan 26. link to original article contains verified protocol PubMed
- Sureda A, Canals C, Arranz R, Caballero D, Ribera JM, Brune M, Passweg J, Martino R, Valcárcel D, Besalduch J, Duarte R, León A, Pascual MJ, García-Noblejas A, López Corral L, Xicoy B, Sierra J, Schmitz N. Allogeneic stem cell transplantation after reduced intensity conditioning in patients with relapsed or refractory Hodgkin's lymphoma. Results of the HDR-ALLO study - a prospective clinical trial by the Grupo Español de Linfomas/Trasplante de Médula Osea (GEL/TAMO) and the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. Haematologica. 2012 Feb;97(2):310-7. Epub 2011 Oct 11. link to original article contains protocol PubMed
Low-dose TBI
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Regimen
Study | Evidence | Comparator |
Gyukocza et al. 2010 | Phase III | Fludarabine and Low-dose TBI |
Preparative regimen
- Total body irradiation (TBI) 2 Gy at a rate of 0.07 to 0.20 Gy/min on day 0
GVHD prophylaxis
- "Postgrafting immunosuppression consisted of cyclosporine or tacrolimus combined with mycophenolate mofetil," further details not specified
References
- Gyurkocza B, Storb R, Storer BE, Chauncey TR, Lange T, Shizuru JA, Langston AA, Pulsipher MA, Bredeson CN, Maziarz RT, Bruno B, Petersen FB, Maris MB, Agura E, Yeager A, Bethge W, Sahebi F, Appelbaum FR, Maloney DG, Sandmaier BM. Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. J Clin Oncol. 2010 Jun 10;28(17):2859-67. Epub 2010 May 3. link to original article contains verified protocol PubMed
(90)YFC
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(90)YFC: Ibritumomab tiuxetan, Fludarabine, Cyclophosphamide
Regimen
Study | Evidence |
Khouri et al. 2012 | Non-randomized |
Preparative regimen
- Rituximab (Rituxan) 250 mg/m2 IV once per day on days -14 & -7
- Ibritumomab tiuxetan & Indium-111 5 mCi IV once on day -14 for dosimetry
- Ibritumomab tiuxetan & Yttrium-90 (Zevalin) 0.4 mCi/kg (15 MBq/kg) (maximum dose of 32 mCi/1.2 GBq) IV once on day -7
- Fludarabine (Fludara) 30 mg/m2 IV once per day on days -5 to -3
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once per day on days -5 to -3
GVHD prophylaxis
- Tacrolimus (Prograf)
- Methotrexate (MTX)
- Antithymocyte globulin, rabbit ATG (Thymoglobulin) as follows:
- Matched unrelated or mismatched donors: 1 mg/kg IV once per day on days -2 & -1
References
- Khouri IF, Saliba RM, Erwin WD, Samuels BI, Korbling M, Medeiros LJ, Valverde R, Alousi AM, Anderlini P, Bashir Q, Ciurea S, Gulbis AM, de Lima M, Hosing C, Kebriaei P, Popat UR, Fowler N, Neelapu SS, Samaniego F, Champlin RE, Macapinlac HA. Nonmyeloablative allogeneic transplantation with or without 90yttrium ibritumomab tiuxetan is potentially curative for relapsed follicular lymphoma: 12-year results. Blood. 2012 Jun 28;119(26):6373-8. Epub 2012 May 14. link to original article contains verified protocol PubMed
Supportive care, hepatic veno-occlusive disease (VOD)
Also known as sinusoidal obstructive syndrome (SOS)
Defibrotide (Defitelio)
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Regimen
Study | Evidence | Comparator |
Richardson et al. 2016 | Phase III | "32 historical controls" |
Regimen details
- Defibrotide (Defitelio) 6.25 mg/kg IV over 2 hours once every 6 hours
Given for at least 21 days. If after 21 days signs and symptoms of VOD have not resolved, give until VOD is resolved, up to a maximum of 60 days.
References
- Richardson PG, Riches ML, Kernan NA, Brochstein JA, Mineishi S, Termuhlen AM, Arai S, Grupp SA, Guinan EC, Martin PL, Steinbach G, Krishnan A, Nemecek ER, Giralt S, Rodriguez T, Duerst R, Doyle J, Antin JH, Smith A, Lehmann L, Champlin R, Gillio A, Bajwa R, D'Agostino RB Sr, Massaro J, Warren D, Miloslavsky M, Hume RL, Iacobelli M, Nejadnik B, Hannah AL, Soiffer RJ. Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure. Blood. 2016 Jan 29. link to original article contains verified protocol PubMed