Difference between revisions of "Allogeneic HSCT"
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| style="background-color:#00CD00" |Phase III | | style="background-color:#00CD00" |Phase III | ||
|[[#Busulfan_.26_Cyclophosphamide|Busulfan & Cyclophosphamide]] | |[[#Busulfan_.26_Cyclophosphamide|Busulfan & Cyclophosphamide]] | ||
− | | style="background-color:# | + | | style="background-color:#91cf60" |Seems to improve 1 & 2 year NRM, similar OS |
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Revision as of 04:41, 17 October 2017
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 allogeneic hematopoietic stem cell transplant (HSCT) conditioning regimens. Unless otherwise specified, the day of hematopoietic stem cell transfusion is by convention day 0.
23 regimens on this page
41 variants on this page
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Myeloablative regimens
Busulfan & Cyclophosphamide
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BuCy: Busulfan & Cyclophosphamide
Regimen
Study | Evidence | Comparator | Efficacy |
Lee et al. 2013 | Phase III | Busulfan & Fludarabine | Seems to have superior OS |
Rambaldi et al. 2015 | Phase III | Busulfan & Fludarabine | Seems to have inferior 1-year non-relapse mortality |
Chemotherapy
- Busulfan (Myleran) 3.2 mg/kg IV once per day on days -7 to -4
- Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day 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 greater than 3000/uL
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
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BuFlu: Busulfan & Fludarabine Flu/Bu: Fludarabine & Busulfan
Regimen #1
Study | Evidence | Comparator | Efficacy |
Rambaldi et al. 2015 | Phase III | Busulfan & Cyclophosphamide | Seems to improve 1 & 2 year NRM, similar OS |
Chemotherapy
- Busulfan (Myleran) 0.8 mg/kg IV four times per day for 2 hour infusions on days -6 to -3
- Fludarabine (Fludara) 30 mg/m2 IV once per day on days -6 to -3
Supportive medications
- Cyclosporine with methotrexate
- For unrelated donors Antithymocyte globulin, rabbit ATG (Thymoglobulin) 0∙5 mg/kg intravenously on day –3 and 2∙0 mg/kg intravenously on day –2 and, if the donor was identical, 2∙5 mg/kg on day –1 (If donor mismatched total ATG dose could be increased to 7.5 mg/kg)
Regimen #2
Study | Evidence | Comparator | Efficacy |
Lee et al. 2013 | Phase III | Busulfan & Cyclophosphamide | Seems to have inferior OS |
Chemotherapy
- Busulfan (Myleran) 3.2 mg/kg IV once per day on days -7 to -4 followed by
- 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 greater than 3000/uL
Regimen #3
Study | Evidence |
Russell et al. 2002 | Phase II |
Chemotherapy
- 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 per day on days -1 & 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
Study | Evidence |
Copelan et al. 2013 | Retrospective |
This was a retrospective study from CIBMTR data; regimen and supportive medication details vary.
Chemoradiotherapy
- 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 link to PMC 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.
Chemoradiotherapy
- TBI 200 cGy twice per day 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.
Chemoradiotherapy
- TBI 220 cGy twice per day in 6 fractions on days –6 to –4 (total dose: 1320 cGy)
- Etoposide (Vepesid) 60 mg/kg IV once on day -3
References
- Rowe JM, Buck G, Burnett AK, Chopra R, Wiernik PH, Richards SM, Lazarus HM, Franklin IM, Litzow MR, Ciobanu N, Prentice HG, Durrant J, Tallman MS, Goldstone AH; ECOG; MRC/NCRI Adult Leukemia Working Party. Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood. 2005 Dec 1;106(12):3760-7. Epub 2005 Aug 16. link to original article contains verified protocol PubMed
- Update: Goldstone AH, Richards SM, Lazarus HM, Tallman MS, Buck G, Fielding AK, Burnett AK, Chopra R, Wiernik PH, Foroni L, Paietta E, Litzow MR, Marks DI, Durrant J, McMillan A, Franklin IM, Luger S, Ciobanu N, Rowe JM. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood. 2008 Feb 15;111(4):1827-33. Epub 2007 Nov 29. link to original article PubMed
- Update: Fielding AK, Rowe JM, Richards SM, Buck G, Moorman AV, Durrant IJ, Marks DI, McMillan AK, Litzow MR, Lazarus HM, Foroni L, Dewald G, Franklin IM, Luger SM, Paietta E, Wiernik PH, Tallman MS, Goldstone AH. Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era: results from the International ALL Trial MRC UKALLXII/ECOG2993. Blood. 2009 May 7;113(19):4489-96. Epub 2009 Feb 24. link to original article link to PMC article PubMed
- Update: Fielding AK, Rowe JM, Buck G, Foroni L, Gerrard G, Litzow MR, Lazarus H, Luger SM, Marks DI, McMillan AK, Moorman AV, Patel B, Paietta E, Tallman MS, Goldstone AH. UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. Blood. 2014 Feb 6;123(6):843-50. Epub 2013 Nov 25. link to original article contains verified protocol link to PMC article PubMed
- 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
Chemotherapy
- 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 ug/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
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 |
Chemotherapy
- 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 |
Chemotherapy
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 per day 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 link to PMC article PubMed
Reduced-intensity conditioning (RIC)
Busulfan & Fludarabine
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Regimen
Study | Evidence |
Devine et al. 2015 (CALGB 100103) | Phase II, <20 pts in subgroup |
This regimen is meant for related donors; only 8 patients received this regimen before the addition of ATG (rabbit) after 2006.
Chemotherapy
- 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 link to PMC article 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.
Chemotherapy
- 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.
Chemotherapy
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.
Chemotherapy
- 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 link to PMC article 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 link to PMC article PubMed
Fludarabine and Low-dose TBI
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Regimen
Study | Evidence |
Maris et al. 2003 | Phase II |
Sorror et al. 2005 | Phase II |
Gyukocza et al. 2010 | Non-randomized |
Details are best described in Maris et al. 2003.
Chemoradiotherapy
- 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 link to PMC 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 link to PMC article 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.
Chemotherapy
- 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 |
Chemotherapy
- 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.
Chemotherapy
- 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 |
Chemotherapy
- 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 link to PMC article PubMed
Fludarabine, Busulfan, ATG, Ibritumomab tiuxetan
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Regimen
Study | Evidence |
Bouabdallah et al. 2015 | Phase II |
Chemoradioimmunotherapy
- 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.
Chemotherapy
- 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.
Chemotherapy
- 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 |
Chemoradiotherapy
- 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 mcg/kg SC once per day, starting on day +1, continued until ANC greater than or equal to 2000/uL for 3 consecutive days
GVHD Prophylaxis
- Mycophenolate mofetil (CellCept) 1000 mg (route not specified) Q8H for patients greater than 50 kg, starting on day -3 "and continuing until day +30 or 7 days after engraftment, whichever was later"
- Patients less than 50 kg received 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 |
Chemoradiotherapy
- 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 per day 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 mcg/kg SC once per day, starting on day +5, continued until ANC greater than or equal to 1000/uL 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 link to PMC article PubMed
Fludarabine & Melphalan
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Regimen #1
Study | Evidence |
Sureda et al. 2011 | Phase II |
Chemotherapy
- 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 on day -2 at 1.5 mg/kg IV BID
- 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 |
Chemotherapy
- 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 link to PMC article 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 link to PMC article PubMed
Low-dose TBI
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TBI: Total Body Irradiation
Regimen
Study | Evidence |
Gyukocza et al. 2010 | Non-randomized |
Radiotherapy
- 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 link to PMC article PubMed
TLI & ATG
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TLI & ATG: Total Lymphocyte Irradiation & Anti-Thymocyte Globulin
Regimen
Study | Evidence |
Lowsky et al. 2005 | Non-randomized |
Kohrt et al. 2009 | Non-randomized |
To be completed
References
- Lowsky R, Takahashi T, Liu YP, Dejbakhsh-Jones S, Grumet FC, Shizuru JA, Laport GG, Stockerl-Goldstein KE, Johnston LJ, Hoppe RT, Bloch DA, Blume KG, Negrin RS, Strober S. Protective conditioning for acute graft-versus-host disease. N Engl J Med. 2005 Sep 29;353(13):1321-31. Erratum in: N Engl J Med. 2006 Feb 23;354(8):884. link to original article PubMed
- Kohrt HE, Turnbull BB, Heydari K, Shizuru JA, Laport GG, Miklos DB, Johnston LJ, Arai S, Weng WK, Hoppe RT, Lavori PW, Blume KG, Negrin RS, Strober S, Lowsky R. TLI and ATG conditioning with low risk of graft-versus-host disease retains antitumor reactions after allogeneic hematopoietic cell transplantation from related and unrelated donors. Blood. 2009 Jul 30;114(5):1099-109. link to original article link to PMC article PubMed
(90)YFC
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(90)YFC: Ibritumomab tiuxetan, Fludarabine, Cyclophosphamide
Regimen
Study | Evidence |
Khouri et al. 2012 | Non-randomized |
Chemoradioimmunotherapy
- 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 link to PMC article PubMed
Supportive care, hepatic veno-occlusive disease (VOD)
Also known as sinusoidal obstructive syndrome (SOS)
Defibrotide monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
Richardson et al. 2016 | Phase III | "32 historical controls" | Seems to have superior survival at day +100 |
Supportive medications
- 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. contains verified protocol link to PMC article PubMed