Allogeneic HSCT

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Section editor
Talal Hilal, MD
Mayo Clinic
Phoenix, AZ, USA

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 before HSCT is day -1, the day of HSCT is day 0, and the day after HSCT is day +1. As with the rest of the HemOnc.org website, the focus here is on regimens used in the treatment of hematologic or oncologic conditions; there are roles for allogeneic HSCT outside of hematology/oncology but these use cases are considered to be out of scope.


These links will take you to highly related pages:

23 regimens on this page
41 variants on this page


Myeloablative regimens, all lines of therapy

BuCyTBI

BuCyTBI: Busulfan, Cyclophosphamide, Total Body Irradiation

Regimen

Study Evidence
Fefer et al. 1979 Pilot, fewer than 20 pts

Chemotherapy

Radiotherapy

  • TBI 920 rads on day 0

Immunotherapy

One course

References

  1. Fefer A, Cheever MA, Thomas ED, Boyd C, Ramberg R, Glucksberg H, Buckner CD, Storb R. Disappearance of Ph1-positive cells in four patients with chronic granulocytic leukemia after chemotherapy, irradiation and marrow transplantation from an identical twin. N Engl J Med. 1979 Feb 15;300(7):333-7. link to original article contains dosing details in manuscript PubMed

Busulfan & Cyclophosphamide

BuCy: Busulfan & Cyclophosphamide

Regimen variant #1, 3.2 x 4/120

Study Dates of enrollment Evidence Comparator Comparative Efficacy Non-relapse mortality
Kröger et al. 2017 (RICMAC) 2004-2012 Phase 3 (C) Bu/Flu RIC allo HSCT Might have inferior OS
Lee et al. 2013 (COSAH C-005) 2005-2009 Phase 3 (C) Busulfan & Fludarabine Seems to have superior OS (secondary endpoint)
Rambaldi et al. 2015 (GITMO-AMLR2) 2008-2012 Phase 3 (C) Busulfan & Fludarabine Seems to have inferior 1-year non-relapse mortality
Zhang et al. 2023 2016-01 to 2020-02 Phase 3 (E-switch-ooc) TBI-Cy Non-inferior OS24 (primary endpoint)
OS24: 76.6% vs 79.4% 		Similar NRM
Xuan et al. 2023 2016-04-18 to 2019-09-30 Phase 3 (C) Busulfan, Cyclophosphamide, Decitabine, G-CSF Inferior CIR24

Chemotherapy

Immunotherapy

GVHD prophylaxis

Supportive therapy

  • Filgrastim (Neupogen) 450 mcg SC once per day, starting on day +5 and continued until ANC greater than 3000/μL

One course


Regimen variant #2, 0.8 x 16/120

Study Dates of enrollment Evidence Comparator Comparative Efficacy Non-relapse mortality
Andersson et al. 2002 1996-06 to 1997-12 Phase 2
Ling et al. 2023 2015-11-20 to 2019-09-30 Phase 3 (C) BuFlu Seems to have inferior TRM12

Chemotherapy

Immunotherapy

One course


Regimen variant #3, 1 x 16/200

Study Evidence
Santos et al. 1983 Non-randomized

Note: the day of allogeneic stem cell transplant is not specified in the protocol.

Chemotherapy

Immunotherapy

One course

References

  1. Santos GW, Tutschka PJ, Brookmeyer R, Saral R, Beschorner WE, Bias WB, Braine HG, Burns WH, Elfenbein GJ, Kaizer H, Mellits D, Sensenbrenner LL, Stuart RK, Yeager AM. Marrow transplantation for acute nonlymphocytic leukemia after treatment with busulfan and cyclophosphamide. N Engl J Med. 1983 Dec 1;309(22):1347-53. link to original article contains dosing details in abstract PubMed
  2. 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 original article contains dosing details in manuscript PubMed
  3. COSAH C-005: 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 dosing details in manuscript PubMed NCT00774280
  4. GITMO-AMLR2: 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 NCT01191957
  5. RICMAC: Kröger N, Iacobelli S, Franke GN, Platzbecker U, Uddin R, Hübel K, Scheid C, Weber T, Robin M, Stelljes M, Afanasyev B, Heim D, Deliliers GL, Onida F, Dreger P, Pini M, Guidi S, Volin L, Günther A, Bethge W, Poiré X, Kobbe G, van Os M, Brand R, de Witte T. Dose-Reduced Versus Standard Conditioning Followed by Allogeneic Stem-Cell Transplantation for Patients With Myelodysplastic Syndrome: A Prospective Randomized Phase III Study of the EBMT (RICMAC Trial). J Clin Oncol. 2017 Jul 1;35(19):2157-2164. Epub 2017 May 2. link to original article PubMed NCT01203228
  6. Zhang H, Fan Z, Huang F, Han L, Xu Y, Xu N, Deng L, Wang S, Lin D, Luo X, Zhang Q, Liu X, Li X, Liang X, Xie S, Qu H, Yu S, Zhou H, Shi P, Xuan L, Lin R, Liu H, Jin H, Sun J, Liu Q. Busulfan Plus Cyclophosphamide Versus Total Body Irradiation Plus Cyclophosphamide for Adults Acute B Lymphoblastic Leukemia: An Open-Label, Multicenter, Phase III Trial. J Clin Oncol. 2023 Jan 10;41(2):343-353. Epub 2022 Sep 9. link to original article link to PMC article contains dosing details in manuscript PubMed NCT02670252
  7. Xuan L, Dai M, Jiang E, Wang Y, Huang F, Fan Z, Xu N, Nie D, Liang X, Chen H, Ye J, Shi P, Liu H, Jin H, Lin R, Yan C, Zhang Y, Sun J, Han M, Liu Q. The effect of granulocyte-colony stimulating factor, decitabine, and busulfan-cyclophosphamide versus busulfan-cyclophosphamide conditioning on relapse in patients with myelodysplastic syndrome or secondary acute myeloid leukaemia evolving from myelodysplastic syndrome undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised, phase 3 trial. Lancet Haematol. 2023 Mar;10(3):e178-e190. Epub 2023 Jan 23. link to original article contains dosing details in abstract PubMed NCT02744742
  8. Ling Y, Xuan L, Xu N, Huang F, Fan Z, Guo Z, Xu X, Liu H, Lin R, Yu S, Zhang H, Jin H, Wu M, Liu C, Liang X, Ou R, Zhang Y, Liu X, Qu H, Zhai X, Sun J, Zhao Y, Liu Q. Busulfan Plus Fludarabine Compared With Busulfan Plus Cyclophosphamide for AML Undergoing HLA-Haploidentical Hematopoietic Cell Transplantation: A Multicenter Randomized Phase III Trial. J Clin Oncol. 2023 Oct 10;41(29):4632-4642. Epub 2023 Jun 19. link to original article contains dosing details in manuscript PubMed NCT02487069

Busulfan, Cyclophosphamide, Decitabine, G-CSF

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Xuan et al. 2023 2016-04-18 to 2019-09-30 Phase 3 (E-esc) BuCy Superior CIR24 (primary endpoint)
CIR24: 10.9% vs 24.8%
(HR 0.39, 95% CI 0.19-0.79)

Chemotherapy

Growth factor therapy

  • G-CSF 5 mcg/kg once per day on days -17 to -10

Immunotherapy

One course

References

  1. Xuan L, Dai M, Jiang E, Wang Y, Huang F, Fan Z, Xu N, Nie D, Liang X, Chen H, Ye J, Shi P, Liu H, Jin H, Lin R, Yan C, Zhang Y, Sun J, Han M, Liu Q. The effect of granulocyte-colony stimulating factor, decitabine, and busulfan-cyclophosphamide versus busulfan-cyclophosphamide conditioning on relapse in patients with myelodysplastic syndrome or secondary acute myeloid leukaemia evolving from myelodysplastic syndrome undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised, phase 3 trial. Lancet Haematol. 2023 Mar;10(3):e178-e190. Epub 2023 Jan 23. link to original article contains dosing details in abstract PubMed NCT02744742

Busulfan & Fludarabine

BuFlu: Busulfan & Fludarabine
Flu/Bu: Fludarabine & Busulfan

Regimen variant #1

Study Dates of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Ling et al. 2023 2015-11-20 to 2019-09-30 Phase 3 (E-de-esc) Busulfan & Cyclophosphamide Seems to have superior TRMM12 (primary endpoint)

Diseases Studied: Acute myeloid leukemia

Chemotherapy

Immunotherapy

One course


Regimen variant #2

Study Dates of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Rambaldi et al. 2015 (GITMO-AMLR2) 2008-2012 Phase 3 (E-switch-ic) Busulfan & Cyclophosphamide Seems to have superior NRM12 (primary endpoint)

Diseases Studied: Acute myeloid leukemia
Graft types studied: Bone Marrow, Mobilized Peripheral Blood Stem Cells

Chemotherapy

GVHD prophylaxis, pre-transplant

  • Antithymocyte globulin, rabbit ATG (Thymoglobulin) by the following donor-based criteria:
    • Matched unrelated donors: 0.5 mg/kg IV once on day -3, then 2 mg/kg IV once on day -2, then 2.5 mg/kg IV once on day -1
    • Mismatched donors: total ATG dose could be increased to 7.5 mg/kg

Immunotherapy

GVHD prophylaxis, post-transplant

One course


Regimen variant #3

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Andersson et al. 2008 1997-2005 Non-randomized Suggested improved outcomes, but shorter follow up
Kanakry et al. 2014 (J0844) 2009-2011 Phase 2
Mielcarek et al. 2016 (FHCC 2541.00) 2011-2013 Phase 2 -

Diseases Studied: Acute myeloid leukemia, Myelodysplastic syndrome, Acute lymphocytic leukemia, Chronic myeloid leukemia, Non-Hodgkin lymphoma
Graft types studied: Matched Related / Unrelated Donor Bone Marrow, Mobilized Peripheral Blood Stem Cells

Chemotherapy

  • Busulfan (Myleran) 130 mg/m2 IV over 3 hours once per day on days -6 to -3
    • Dosing targeted for optimal pharmacokinetics but different parameters each institution, please consult the original publication for optimal levels
  • Fludarabine (Fludara) 40 mg/m2 IV over 60 minutes once per day on days -6 to -3, given first

GVHD prophylaxis, pre-transplant

Immunotherapy

GVHD prophylaxis, post-transplant

#1 Tacrolimus & methotrexate based (Andersson et al.)

Supportive therapy

  • All patients received Filgrastim (Neupogen) SC once per day from day +7 until achieving an absolute neutrophil count (ANC) ≥1.5 × 109/L for three days
  • Phenytoin (Dilantin) prophylaxis used during and for one day after IV busulfan

#2 Post-Transplant Cy based (Kanakry et al. and FHCC 2541.00)

GVHD prophylaxis

  • Cyclophosphamide (Cytoxan) 50 mg/kg IV once per day on days +3 & +4 (used alone in Kanakry et al. when all patients received bone marrow grafts)
  • ± Cyclosporine intravenous loading dose of CSP was given on day 5, followed by subsequent twice per day dosing adjusted to maintain whole blood trough at 120 to 360 ng/mL. In abscence of GVHD Cyclosporine was tapered from day +56 through day +126 (used in FHCC 2541.00 with PBSCT grafts)

Supportive therapy

One course


Regimen variant #4

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Lee et al. 2013 (COSAH C-005) 2005-2009 Phase 3 (E-switch-ic) Busulfan & Cyclophosphamide Seems to have inferior OS (secondary endpoint)

Diseases Studied: Acute myeloid leukemia, Myelodysplastic syndrome, Acute lymphocytic leukemia, Chronic myeloid leukemia, Myelofibrosis
Graft types studied: Matched Related / Unrelated Donor Bone Marrow, Mobilized Peripheral Blood Stem Cells

Chemotherapy

  • Busulfan (Myleran) 3.2 mg/kg IV once per day on days -7 to -4, given first on days overlapping with fludarabine (total dose: 12.8 mg/kg)
  • Fludarabine (Fludara) 30 mg/m2 IV once per day on days -6 to -2, given second on days overlapping with busulfan

Immunotherapy

GVHD prophylaxis

Supportive therapy

  • Filgrastim (Neupogen) 450 mcg SC once per day, starting on day +5 and continued until ANC greater than 3000/μL

One course


Regimen variant #5

Study Dates of enrollment Evidence
Russell et al. 2002 1999-2001 Phase 2

Diseases Studied: Acute myeloid leukemia, Myelodysplastic syndrome, Chronic myeloid leukemia, Chronic lymphocytic leukemia, Non-Hodgkin lymphoma, Hypereosinophilic syndrome
Graft types studied: Matched Related / Unrelated Donor Bone Marrow or Mobilized Peripheral Blood Stem Cells

Chemotherapy

Immunotherapy

GVHD prophylaxis

Supportive therapy

  • Leucovorin (Folinic acid) 5 mg started 24 hours after each dose of methotrexate and continued every 6 hours until 12 hours before the next dose of methotrexate
  • Phenytoin (Dilantin) "loading" PO/IV, dosed to maintain therapeutic levels of 40 to 80 umol/L on days -5 to -2

One course

References

  1. 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 dosing details in manuscript PubMed
  2. de Lima M, Couriel D, Thall PF, Wang X, Madden T, Jones R, Shpall EJ, Shahjahan M, Pierre B, Giralt S, Korbling M, Russell JA, Champlin RE, Andersson BS. Once-daily intravenous busulfan and fludarabine: clinical and pharmacokinetic results of a myeloablative, reduced-toxicity conditioning regimen for allogeneic stem cell transplantation in AML and MDS. Blood. 2004 Aug 1;104(3):857-64. Epub 2004 Apr 8. link to original article PubMed
  3. Andersson BS, de Lima M, Thall PF, Wang X, Couriel D, Korbling M, Roberson S, Giralt S, Pierre B, Russell JA, Shpall EJ, Jones RB, Champlin RE. Once daily IV busulfan and fludarabine (IV Bu-Flu) compares favorably with IV busulfan and cyclophosphamide (IV BuCy2) as pretransplant conditioning therapy in AML/MDS. Biol Blood Marrow Transplant. 2008;14(6):672-84. link to original article link to PMC article contains dosing details in manuscript PubMed
  4. COSAH C-005: 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 dosing details in manuscript PubMed NCT00774280
  5. J0844: Kanakry CG, O'Donnell PV, Furlong T, de Lima MJ, Wei W, Medeot M, Mielcarek M, Champlin RE, Jones RJ, Thall PF, Andersson BS, Luznik L. Multi-institutional study of post-transplantation cyclophosphamide as single-agent graft-versus-host disease prophylaxis after allogeneic bone marrow transplantation using myeloablative busulfan and fludarabine conditioning. J Clin Oncol. 2014; 32(31):3497-505. Epub 2014 Sep 29. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00809276
  6. FHCC 2541.00: Mielcarek M, Furlong T, O'Donnell PV, Storer BE, McCune JS, Storb R, Carpenter PA, Flowers ME, Appelbaum FR, Martin PJ. Posttransplantation cyclophosphamide for prevention of graft-versus-host disease after HLA-matched mobilized blood cell transplantation. Blood. 2016;127(11):1502-8. Epub 2016 Jan 13. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01427881
  7. GITMO-AMLR2: 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 NCT01191957
  8. MDACC 2011-0628: Andersson BS, Thall PF, Ma J, Valdez BC, Bassett R Jr, Chen J, Ahmed S, Alousi A, Bashir Q, Ciurea S, Gulbis A, Cool R, Kawedia J, Hosing C, Kebriaei P, Kornblau S, Myers A, Oran B, Rezvani K, Shah N, Shpall E, Parmar S, Popat UR, Nieto Y, Champlin RE. A randomized phase III study of pretransplant conditioning for AML/MDS with fludarabine and once daily IV busulfan ± clofarabine in allogeneic stem cell transplantation. Bone Marrow Transplant. 2022 Aug;57(8):1295-1303. Epub 2022 May 24. link to original article link to PMC article PubMed NCT01471444
  9. Ling Y, Xuan L, Xu N, Huang F, Fan Z, Guo Z, Xu X, Liu H, Lin R, Yu S, Zhang H, Jin H, Wu M, Liu C, Liang X, Ou R, Zhang Y, Liu X, Qu H, Zhai X, Sun J, Zhao Y, Liu Q. Busulfan Plus Fludarabine Compared With Busulfan Plus Cyclophosphamide for AML Undergoing HLA-Haploidentical Hematopoietic Cell Transplantation: A Multicenter Randomized Phase III Trial. J Clin Oncol. 2023 Oct 10;41(29):4632-4642. Epub 2023 Jun 19. link to original article contains dosing details in manuscript PubMed NCT02487069

Cyclophosphamide & TBI

Cy/TBI: Cyclophosphamide & Total Body Irradiation
TBI-CY: Total Body Irradiation & Cyclophosphamide

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy Non-relapse mortality
Rudolph et al. 1973 1968-1970 Non-randomized
Fefer et al. 1982 1971-1980 Non-randomized, fewer than 20 pts
Thomas et al. 1979 1976-1977 Non-randomized
Blume et al. 1980 1976-1979 Non-randomized, fewer than 20 pts
Johnson et al. 1981 1976-1980 Non-randomized
Brochstein et al. 1987 1979-1985 Non-randomized
Goldman et al. 1986 1981-1984 Non-randomized
Kersey et al. 1987 1982-1985 Quasi-randomized Auto HSCT Superior RFS
Hansen et al. 1998 1985-1994 Non-randomized
Sebban et al. 1994 (LALA 87) 1986-1991 Phase 3 (E-esc) Chemotherapy or Auto HSCT Did not meet co-primary endpoints of DFS/OS
Zittoun et al. 1995 1986-1993 Phase 3 (E-esc) Intensive chemotherapy Superior DFS
Thomas et al. 2004 (LALA-94) 1994-2002 Non-randomized part of RCT
Bornhäuser et al. 2012 (9005-2003) 2004-2009 Phase 3 (C) Fludarabine & TBI Did not meet primary endpoint of NRM
Zhang et al. 2023 2016-01 to 2020-02 Phase 3 (C) BuCy Non-inferior OS24 Similar NRM

Details in most of the manuscripts are limited.

Chemotherapy

Radiotherapy

  • Total body irradiation by the following study-specific criteria:
    • Zhang et al. 2023: 450 cGy once per day on days -5 & -4 (900 cGy total)
    • Other studies: 10 to 1200 cGy total

Immunotherapy

One course

References

  1. Rudolph RH, Fefer A, Thomas ED, Buckner CD, Clift RA, Storb R. Isogeneic marrow grafts for hematologic malignancy in man. Arch Intern Med. 1973 Aug;132(2):279-85. link to original article PubMed
    1. Update: Fefer A, Einstein AB, Thomas ED, Buckner CD, Clift RA, Glucksberg H, Neiman PE, Storb R. Bone-marrow transplantation for hematologic neoplasia in 16 patients with identical twins. N Engl J Med. 1974 Jun 20;290(25):1389-93. link to original article PubMed
  2. Thomas ED, Sanders JE, Flournoy N, Johnson FL, Buckner CD, Clift RA, Fefer A, Goodell BW, Storb R, Weiden PL. Marrow transplantation for patients with acute lymphoblastic leukemia in remission. Blood. 1979 Aug;54(2):468-76. link to original article contains dosing details in abstract PubMed
  3. Blume KG, Beutler E, Bross KJ, Chillar RK, Ellington OB, Fahey JL, Farbstein MJ, Forman SJ, Schmidt GM, Scott EP, Spruce WE, Turner MA, Wolf JL. Bone-marrow ablation and allogeneic marrow transplantation in acute leukemia. N Engl J Med. 1980 May 8;302(19):1041-6. link to original article PubMed
  4. Johnson FL, Thomas ED, Clark BS, Chard RL, Hartmann JR, Storb R. A comparison of marrow transplantation with chemotherapy for children with acute lymphoblastic leukemia in second or subsequent remission. N Engl J Med. 1981 Oct 8;305(15):846-51. link to original article PubMed
  5. Fefer A, Cheever MA, Greenberg PD, Appelbaum FR, Boyd CN, Buckner CD, Kaplan HG, Ramberg R, Sanders JE, Storb R, Thomas ED. Treatment of chronic granulocytic leukemia with chemoradiotherapy and transplantation of marrow from identical twins. N Engl J Med. 1982 Jan 14;306(2):63-8. link to original article PubMed
  6. Goldman JM, Apperley JF, Jones L, Marcus R, Goolden AW, Batchelor R, Hale G, Waldmann H, Reid CD, Hows J, Gordon-Smith E, Catovsky D, Galton DAG. Bone marrow transplantation for patients with chronic myeloid leukemia. N Engl J Med. 1986 Jan 23;314(4):202-7. PubMed
  7. Kersey JH, Weisdorf D, Nesbit ME, LeBien TW, Woods WG, McGlave PB, Kim T, Vallera DA, Goldman AI, Bostrom B, Hurd D, Ramsay NKC. Comparison of autologous and allogeneic bone marrow transplantation for treatment of high-risk refractory acute lymphoblastic leukemia. N Engl J Med. 1987 Aug 20;317(8):461-7. link to original article PubMed
  8. Brochstein JA, Kernan NA, Groshen S, Cirrincione C, Shank B, Emanuel D, Laver J, O'Reilly RJ. Allogeneic bone marrow transplantation after hyperfractionated total-body irradiation and cyclophosphamide in children with acute leukemia. N Engl J Med. 1987 Dec 24;317(26):1618-24. link to original article PubMed
  9. LALA 87: Sebban C, Lepage E, Vernant JP, Gluckman E, Attal M, Reiffers J, Sutton L, Racadot E, Michallet M, Maraninchi D, Dreyfus F, Fiere D; French Group of Therapy of Adult Acute Lymphoblastic Leukemia. Allogeneic bone marrow transplantation in adult acute lymphoblastic leukemia in first complete remission: a comparative study. J Clin Oncol. 1994 Dec;12(12):2580-7. link to original article PubMed
    1. Update: Thiebaut A, Vernant JP, Degos L, Huguet FR, Reiffers J, Sebban C, Lepage E, Thomas X, Fière D. Adult acute lymphocytic leukemia study testing chemotherapy and autologous and allogeneic transplantation: a follow-up report of the French protocol LALA 87. Hematol Oncol Clin North Am. 2000 Dec;14(6):1353-66. link to original article PubMed
  10. Zittoun RA, Mandelli F, Willemze R, de Witte T, Labar B, Resegotti L, Leoni F, Damasio E, Visani G, Papa G, Caronia F, Hayat M, Stryckmans P, Rotoli B, Leoni P, Peetermans ME, Dardenne M, Vegna ML, Petti MC, Solbu G, Suciu S; EORTC; Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto. Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. N Engl J Med. 1995 Jan 26;332(4):217-23. link to original article contains dosing details in abstract PubMed
  11. Hansen JA, Gooley TA, Martin PJ, Appelbaum F, Chauncey TR, Clift RA, Petersdorf EW, Radich J, Sanders JE, Storb RF, Sullivan KM, Anasetti C. Bone marrow transplants from unrelated donors for patients with chronic myeloid leukemia. N Engl J Med. 1998 Apr 2;338(14):962-8. link to original article PubMed
  12. LALA-94: Thomas X, Boiron JM, Huguet F, Dombret H, Bradstock K, Vey N, Kovacsovics T, Delannoy A, Fegueux N, Fenaux P, Stamatoullas A, Vernant JP, Tournilhac O, Buzyn A, Reman O, Charrin C, Boucheix C, Gabert J, Lhéritier V, Fiere D. Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial. J Clin Oncol. 2004 Oct 15;22(20):4075-86. Epub 2004 Sep 7. link to original article contains dosing details in manuscript PubMed NCT00002700
    1. Update: Vey N, Thomas X, Picard C, Kovascovicz T, Charin C, Cayuela JM, Dombret H, Dastugue N, Huguet F, Bastard C, Stamatoulas A, Giollant M, Tournilhac O, Macintyre E, Buzyn A, Bories D, Kuentz M, Dreyfus F, Delannoy A, Raynaud S, Gratecos N, Bordessoule D, de Botton S, Preudhomme C, Reman O, Troussard X, Pigneux A, Bilhou C, Vernant JP, Boucheix C, Gabert J; Swiss Group for Clinical Cancer Research. Allogeneic stem cell transplantation improves the outcome of adults with t(1;19)/E2A-PBX1 and t(4;11)/MLL-AF4 positive B-cell acute lymphoblastic leukemia: results of the prospective multicenter LALA-94 study. Leukemia. 2006 Dec;20(12):2155-61. Epub 2006 Oct 12. link to original article PubMed
  13. 9005-2003: Bornhäuser M, Kienast J, Trenschel R, Burchert A, Hegenbart U, Stadler M, Baurmann H, Schäfer-Eckart K, Holler E, Kröger N, Schmid C, Einsele H, Kiehl MG, Hiddemann W, Schwerdtfeger R, Buchholz S, Dreger P, Neubauer A, Berdel WE, Ehninger G, Beelen DW, Schetelig J, Stelljes M. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol. 2012 Oct;13(10):1035-44. Epub 2012 Sep 7. link to original article contains dosing details in abstract PubMed NCT00150878
  14. 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
  15. Zhang H, Fan Z, Huang F, Han L, Xu Y, Xu N, Deng L, Wang S, Lin D, Luo X, Zhang Q, Liu X, Li X, Liang X, Xie S, Qu H, Yu S, Zhou H, Shi P, Xuan L, Lin R, Liu H, Jin H, Sun J, Liu Q. Busulfan Plus Cyclophosphamide Versus Total Body Irradiation Plus Cyclophosphamide for Adults Acute B Lymphoblastic Leukemia: An Open-Label, Multicenter, Phase III Trial. J Clin Oncol. 2023 Jan 10;41(2):343-353. Epub 2022 Sep 9. link to original article link to PMC article contains dosing details in manuscript PubMed NCT02670252
  16. SWOG S9920: NCT00005866

Etoposide & TBI

Regimen variant #1, weight-based etoposide

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Balduzzi et al. 2005 1995-2000 Quasi-randomized Chemotherapy Seems to have superior DFS
Peters et al. 2015 (ALL-SCT-BFM 2003) 2003-2011 Non-randomized

This regimen was evaluated in the treatment of high-risk pediatric acute lymphoblastic leukemia in CR1.

Chemotherapy

Radiotherapy

Immunotherapy

One course


Regimen variant #2, BSA-based etoposide

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Peters et al. 2020 (FORUM) 2013-2018 Phase 3 (C) 1a. Busulfan, Fludarabine, Thiotepa
1b. Fludarabine, Thiotepa, Treosulfan 		Superior OS (primary endpoint)

This regimen was evaluated in the treatment of high-risk pediatric acute lymphoblastic leukemia in CMR.

Chemotherapy

Radiotherapy

Immunotherapy

One course


Regimen variant #3, 1320 cGy

Study Dates of enrollment Evidence
Rowe et al. 2005 (MRC UKALL XII/ECOG E2993) 1993-2003 Non-randomized part of phase 3 RCT

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.

Chemotherapy

Radiotherapy

Immunotherapy

One course

References

  1. Balduzzi A, Valsecchi MG, Uderzo C, De Lorenzo P, Klingebiel T, Peters C, Stary J, Felice MS, Magyarosy E, Conter V, Reiter A, Messina C, Gadner H, Schrappe M. Chemotherapy versus allogeneic transplantation for very-high-risk childhood acute lymphoblastic leukaemia in first complete remission: comparison by genetic randomisation in an international prospective study. Lancet. 2005 Aug 20-26;366(9486):635-42. link to original article contains dosing details in manuscript PubMed
  2. MRC UKALL XII/ECOG E2993: Rowe JM, Buck G, Burnett AK, Chopra R, Wiernik PH, Richards SM, Lazarus HM, Franklin IM, Litzow MR, Ciobanu N, Prentice HG, Durrant J, Tallman MS, Goldstone AH; ECOG; MRC/NCRI Adult Leukemia Working Party. Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood. 2005 Dec 1;106(12):3760-7. Epub 2005 Aug 16. link to original article contains dosing details in manuscript PubMed NCT00002514
    1. Update: Goldstone AH, Richards SM, Lazarus HM, Tallman MS, Buck G, Fielding AK, Burnett AK, Chopra R, Wiernik PH, Foroni L, Paietta E, Litzow MR, Marks DI, Durrant J, McMillan A, Franklin IM, Luger S, Ciobanu N, Rowe JM. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood. 2008 Feb 15;111(4):1827-33. Epub 2007 Nov 29. link to original article PubMed
    2. Update: Fielding AK, Rowe JM, Richards SM, Buck G, Moorman AV, Durrant IJ, Marks DI, McMillan AK, Litzow MR, Lazarus HM, Foroni L, Dewald G, Franklin IM, Luger SM, Paietta E, Wiernik PH, Tallman MS, Goldstone AH. Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era: results from the International ALL Trial MRC UKALLXII/ECOG2993. Blood. 2009 May 7;113(19):4489-96. Epub 2009 Feb 24. link to original article link to PMC article PubMed
    3. Update: Fielding AK, Rowe JM, Buck G, Foroni L, Gerrard G, Litzow MR, Lazarus H, Luger SM, Marks DI, McMillan AK, Moorman AV, Patel B, Paietta E, Tallman MS, Goldstone AH. UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. Blood. 2014 Feb 6;123(6):843-50. Epub 2013 Nov 25. link to original article contains dosing details in manuscript link to PMC article PubMed
  3. ALL-SCT-BFM-2003: 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 NCT01423747
  4. FORUM: Peters C, Dalle JH, Locatelli F, Poetschger U, Sedlacek P, Buechner J, Shaw PJ, Staciuk R, Ifversen M, Pichler H, Vettenranta K, Svec P, Aleinikova O, Stein J, Güngör T, Toporski J, Truong TH, Diaz-de-Heredia C, Bierings M, Ariffin H, Essa M, Burkhardt B, Schultz K, Meisel R, Lankester A, Ansari M, Schrappe M, von Stackelberg A, Balduzzi A, Corbacioglu S, Bader P; IBFM Study Group; IntReALL Study Group; I-BFM SCT Study Group; EBMT Paediatric Diseases Working Party. Total Body Irradiation or Chemotherapy Conditioning in Childhood ALL: A Multinational, Randomized, Noninferiority Phase III Study. J Clin Oncol. 2021 Feb 1;39(4):295-307. Epub 2020 Dec 17. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01949129

Fludarabine, Busulfan, Cyclophosphamide

FluBuCy: Fludarabine, Busulfan, Cyclophosphamide

Regimen variant #1, oral

Study Dates of enrollment Evidence
Glass et al. 2014 (DSHNHL R3) 2004-06-16 to 2009-03-24 Phase 2

This is described by the authors as a lymphoma-directed myeloablative conditioning regimen

Chemotherapy

Immunotherapy

GVHD prophylaxis

One course


Regimen variant #2, intravenous

Study Dates of enrollment Evidence
Glass et al. 2014 (DSHNHL R3) 2004-06-16 to 2009-03-24 Phase 2

This is described by the authors as a lymphoma-directed myeloablative conditioning regimen

Chemotherapy

Immunotherapy

GVHD prophylaxis

One course

References

  1. DSHNHL R3: 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; 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 dosing details in manuscript PubMed NCT00785330

Fludarabine & TBI for haploidentical transplant

Flu/TBI: Fludarabine and Total Body Irradiation

Regimen

Study Dates of enrollment Evidence
Soloman et al. 2014 2012-04 to 2014-05 Phase 2

Chemotherapy

Radiotherapy

Immunotherapy

GVHD prophylaxis

  • Cyclophosphamide (Cytoxan) 50 mg/kg IBW IV over 1 to 2 hours once per day on days +3 & +4, started 60 to 72 hours after marrow infusion
  • Mycophenolate mofetil (CellCept) 15 mg/kg (maximum daily dose of 3000 mg; route not specified) every 8 hours, 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

One course

References

  1. Solomon SR, Sizemore CA, Sanacore M, Zhang X, Brown S, Holland HK, Morris LE, Bashey A. Total Body Irradiation-Based Myeloablative Haploidentical Stem Cell Transplantation Is a Safe and Effective Alternative to Unrelated Donor Transplantation in Patients Without Matched Sibling Donors. Biol Blood Marrow Transplant. 2015 Jul;21(7):1299-307. Epub 2015 Mar 19. link to original article contains dosing details in manuscript PubMed

BEAM

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

Regimen variant #1

Study Evidence
Przepiorka et al. 1999 Phase 2

Chemotherapy

Immunotherapy

GVHD prophylaxis

Supportive therapy

  • "Prophylactic antibiotics"
  • Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day +7 and continued until engraftment

One course


Regimen variant #2, attenuated

Study Dates of enrollment Evidence
Sobol et al. 2013 2000-05 to 2012-04 Phase 2

Chemotherapy

Immunotherapy

GVHD prophylaxis

One course

References

  1. 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 dosing details in abstract PubMed
  2. 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 contains dosing details in manuscript PubMed

BFR

BFR: Bendamustine, Fludarabine, Rituximab

Regimen

Study Dates of enrollment Evidence
Khouri et al. 2014 (MDACC 2008-0246) 2009-04 to 2013-02 Phase 2

Chemotherapy

Targeted therapy

Immunotherapy

GVHD prophylaxis

  • See article for GVHD prophylaxis information

One course

References

  1. MDACC 2008-0246: 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 dosing details in manuscript link to PMC article PubMed NCT00880815

Reduced-intensity conditioning (RIC), all lines of therapy

Busulfan & Fludarabine

BuFlu: Busulfan & Fludarabine
Flu/Bu: Fludarabine & Busulfan

Regimen variant #1, 90/6.4

Study Dates of enrollment Evidence Comparator Comparative Efficacy
de Masson et al. 2023 (CUTALLO) 2016-06-01 to 2022-03-03 Propensity score analysis (E-esc) No transplant Superior PFS (primary endpoint)
Median PFS: 9 vs 3 mo
(HR 0.38, 95% CI 0.21-0.69)

Diseases Studied: Cutaneous T-cell lymphoma

Chemotherapy

Immunotherapy

GVHD prophylaxis

  • Cyclosporine started on day -1, tapered on day +90 if no GVHD
  • Methotrexate (MTX) 15 mg/m2 IV once on day +1, then 10 mg/m2 IV once per day on days +3, +6, +11

One course


Regimen variant #2, 125/4

Study Dates of enrollment Evidence
Garban et al. 2006 (IFM99-03) 2000-04 to 2004-09 Non-randomized

This regimen was meant for patients who had an HLA-identical sibling donor, and was evaluated in multiple myeloma patients.

Chemotherapy

Immunotherapy

GVHD prophylaxis

One course

Dose and schedule modifications

  • Cyclosporine doses adjusted to "serum levels", tapered on day +60 to off by day +100 (if no GVHD)


Regimen variant #3, 150/6.4

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Devine et al. 2015 (CALGB 100103) 2004-2011 Phase 2
Beelen et al. 2019 (MC-FludT.14/L) 2013-2016 Phase 3 (C) Fludarabine & Treosulfan Non-inferior EFS24

This regimen is meant for related donors; in CALGB 100103, 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
    • MC-FludT.14/L gave the doses on days -6 to -2
  • Busulfan (Myleran) 0.8 mg/kg IV over 2 hours every 6 hours on days -4 & -3 (total dose: 6.4 mg/kg)

Immunotherapy

GVHD prophylaxis

  • ATG (Rabbit) 2.5 mg/kg IV over 6 hours once per day on days -4 to -2
  • 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

One course


Regimen variant #4, 150/360

Study Dates of enrollment Evidence
Mohty et al. 2014 (ITT 08-01) 2009-2011 Phase 2

Chemotherapy

GVHD prophylaxis

Immunotherapy

One course


Regimen variant #5, 180/8

Study Evidence
Slavin et al. 1998 Phase 2
Schetelig et al. 2003 Phase 2

Chemotherapy

GVHD prophylaxis

  • ATG-Fresenius 10 mg/kg IV once per day on days -4 to -1 (4 consecutive days)

Immunotherapy

One course

References

  1. 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 dosing details in manuscript PubMed
  2. Schetelig J, Thiede C, Bornhauser M, Schwerdtfeger R, Kiehl M, Beyer J, Sayer HG, Kroger N, Hensel M, Scheffold C, Held TK, Hoffken K, Ho AD, Kienast J, Neubauer A, Zander AR, Fauser AA, Ehninger G, Siegert W; Cooperative German Transplant Study Group. Evidence of a graft-versus-leukemia effect in chronic lymphocytic leukemia after reduced-intensity conditioning and allogeneic stem-cell transplantation: the Cooperative German Transplant Study Group. J Clin Oncol. 2003 Jul 15;21(14):2747-53. link to original article contains reference to protocol PubMed
  3. IFM99-03: 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 dosing details in manuscript PubMed
    1. Pooled 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. 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
  4. ITT 08-01: 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 dosing details in manuscript PubMed NCT00841724
  5. CALGB 100103: 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 dosing details in manuscript link to PMC article PubMed NCT00070135
  6. MC-FludT.14/L: Beelen DW, Trenschel R, Stelljes M, Groth C, Masszi T, Reményi P, Wagner-Drouet EM, Hauptrock B, Dreger P, Luft T, Bethge W, Vogel W, Ciceri F, Peccatori J, Stölzel F, Schetelig J, Junghanß C, Grosse-Thie C, Michallet M, Labussiere-Wallet H, Schaefer-Eckart K, Dressler S, Grigoleit GU, Mielke S, Scheid C, Holtick U, Patriarca F, Medeot M, Rambaldi A, Micò MC, Niederwieser D, Franke GN, Hilgendorf I, Winkelmann NR, Russo D, Socié G, Peffault de Latour R, Holler E, Wolff D, Glass B, Casper J, Wulf G, Menzel H, Basara N, Bieniaszewska M, Stuhler G, Verbeek M, Grass S, Iori AP, Finke J, Benedetti F, Pichlmeier U, Hemmelmann C, Tribanek M, Klein A, Mylius HA, Baumgart J, Dzierzak-Mietla M, Markiewicz M. Treosulfan or busulfan plus fludarabine as conditioning treatment before allogeneic haemopoietic stem cell transplantation for older patients with acute myeloid leukaemia or myelodysplastic syndrome (MC-FludT.14/L): a randomised, non-inferiority, phase 3 trial. Lancet Haematol. 2020 Jan;7(1):e28-e39. Epub 2019 Oct 9. link to original article contains dosing details in abstract PubMed NCT00822393
  7. CUTALLO: de Masson A, Beylot-Barry M, Ram-Wolff C, Mear JB, Dalle S, d'Incan M, Ingen-Housz-Oro S, Orvain C, Abraham J, Dereure O, Charbonnier A, Cornillon J, Longvert C, Barete S, Boulinguez S, Wierzbicka-Hainaut E, Aubin F, Rubio MT, Bernard M, Schmidt-Tanguy A, Houot R, Pham-Ledard A, Michonneau D, Brice P, Labussière-Wallet H, Bouaziz JD, Grange F, Moins-Teisserenc H, Jondeau K, Michel L, Mourah S, Battistella M, Daguindau E, Loschi M, Picard A, Franck N, Maillard N, Huynh A, Nguyen S, Marçais A, Chaby G, Ceballos P, Le Corre Y, Maury S, Bay JO, Adamski H, Bachy E, Forcade E, Socié G, Bagot M, Chevret S, Peffault de Latour R; CUTALLO Investigators; Groupe Français d'Etude des Lymphomes Cutanés; Société Française de Greffe de Moëlle et Thérapie Cellulaire. Allogeneic transplantation in advanced cutaneous T-cell lymphomas (CUTALLO): a propensity score matched controlled prospective study. Lancet. 2023 Jun 10;401(10392):1941-1950. Epub 2023 Apr 24. link to original article contains dosing details in supplement PubMed NCT02520908

Busulfan, Fludarabine, Ibritumomab tiuxetan

Regimen

Study Evidence
Bouabdallah et al. 2015 (ZEVALLO) Phase 2

Chemotherapy

Targeted therapy

Radioconjugate therapy

Immunotherapy

GVHD prophylaxis

One course

References

  1. ZEVALLO: 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 dosing details in manuscript PubMed NCT00607854

Busulfan, Fludarabine, Thiotepa

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
de Masson et al. 2023 (CUTALLO) 2016-06-01 to 2022-03-03 Propensity score analysis (E-esc) No transplant Superior PFS (primary endpoint)
Median PFS: 9 vs 3 mo
(HR 0.38, 95% CI 0.21-0.69)

Diseases Studied: Cutaneous T-cell lymphoma

Note: this preparative regimen was intended for haploidentical HSCT.

Chemotherapy

Immunotherapy

GVHD prophylaxis

One course

References

  1. CUTALLO: de Masson A, Beylot-Barry M, Ram-Wolff C, Mear JB, Dalle S, d'Incan M, Ingen-Housz-Oro S, Orvain C, Abraham J, Dereure O, Charbonnier A, Cornillon J, Longvert C, Barete S, Boulinguez S, Wierzbicka-Hainaut E, Aubin F, Rubio MT, Bernard M, Schmidt-Tanguy A, Houot R, Pham-Ledard A, Michonneau D, Brice P, Labussière-Wallet H, Bouaziz JD, Grange F, Moins-Teisserenc H, Jondeau K, Michel L, Mourah S, Battistella M, Daguindau E, Loschi M, Picard A, Franck N, Maillard N, Huynh A, Nguyen S, Marçais A, Chaby G, Ceballos P, Le Corre Y, Maury S, Bay JO, Adamski H, Bachy E, Forcade E, Socié G, Bagot M, Chevret S, Peffault de Latour R; CUTALLO Investigators; Groupe Français d'Etude des Lymphomes Cutanés; Société Française de Greffe de Moëlle et Thérapie Cellulaire. Allogeneic transplantation in advanced cutaneous T-cell lymphomas (CUTALLO): a propensity score matched controlled prospective study. Lancet. 2023 Jun 10;401(10392):1941-1950. Epub 2023 Apr 24. link to original article contains dosing details in supplement PubMed NCT02520908

Clofarabine & Melphalan

Regimen

Study Evidence
Middeke et al. 2015 (BRIDGE) Phase 2

Limited details are available in the abstract. Treatment is meant to be given during aplasia.

Preceding treatment

Chemotherapy

Immunotherapy

One course

References

  1. BRIDGE: 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 dosing details in abstract PubMed

Cyclophosphamide, Fludarabine, Thiotepa

Regimen

Study Evidence
Corradini et al. 2002 Non-randomized

Chemotherapy

  • Cyclophosphamide (Cytoxan) 30 mg/kg IV once per day on days -4 & -3
  • Fludarabine (Fludara) 30 mg/m2 IV once per day on days -4 & -3, given 4 hours after cyclophosphamide
  • Thiotepa (Thioplex) by the following age-based criteria:
    • Younger than 45 years old: 7.5 mg/kg IV once every 12 hours on day -6 (total dose 15 mg/kg)
    • 45 to 60 years old: 5 mg/kg IV once every 12 hours on day -6 (total dose 10 mg/kg)
    • Older than 60 years old: 2.5 mg/kg IV once every 12 hours on day -6 (total dose 5 mg/kg)

Immunotherapy

One course

References

  1. 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 contains dosing details in manuscript PubMed

Cyclophosphamide & Fludarabine (FC)

FC: Fludarabine & Cyclophosphamide
FluCy: Fludarabine & Cyclophosphamide

Regimen variant #1, 150/2500

Study Evidence
Dreger et al. 2010 (GCLLSG CLL3X) Phase 2

Chemotherapy

GVHD prophylaxis

  • ATG-Fresenius by the following donor-based criteria:
    • Unrelated donors: 10 mg/kg/day IV on days -4 to -1 (4 consecutive days)

Immunotherapy

One course


Regimen variant #2, 125/120

Study Evidence
Childs et al. 2000 Non-randomized, fewer than 20 pts

Chemotherapy

Immunotherapy

One course

References

  1. Childs R, Chernoff A, Contentin N, Bahceci E, Schrump D, Leitman S, Read EJ, Tisdale J, Dunbar C, Linehan WM, Young NS, Clave E, Epperson D, Mayo V, Barrett AJ. Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation. N Engl J Med. 2000 Sep 14;343(11):750-8. link to original article contains dosing details in manuscript PubMed
  2. GCLLSG CLL3X: 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 dosing details in manuscript PubMed NCT00281983
    1. 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
    2. Update: Krämer I, Stilgenbauer S, Dietrich S, Böttcher S, Zeis M, Stadler M, Bittenbring J, Uharek L, Scheid C, Hegenbart U, Ho A, Hallek M, Kneba M, Schmitz N, Döhner H, Dreger P. Allogeneic hematopoietic cell transplantation for high-risk CLL: 10-year follow-up of the GCLLSG CLL3X trial. Blood. 2017 Sep 21;130(12):1477-1480. Epub 2017 Jul 17. link to original article PubMed

FBM

FBM: Fludarabine, BCNU (Carmustine), Melphalan

Regimen variant #1

Study Dates of enrollment Evidence
Marks et al. 2008 1998-2003 Phase 2

Note: this variant is intended for patients younger than 55 years of age.

Chemotherapy

Immunotherapy

One course


Regimen variant #2

Study Dates of enrollment Evidence
Marks et al. 2008 1998-2003 Phase 2

Note: this variant is intended for patients 55 years of age and older.

Chemotherapy

Immunotherapy

One course

References

  1. Marks R, Potthoff K, Hahn J, Ihorst G, Bertz H, Spyridonidis A, Holler E, Finke JM. Reduced-toxicity conditioning with fludarabine, BCNU, and melphalan in allogeneic hematopoietic cell transplantation: particular activity against advanced hematologic malignancies. Blood. 2008 Jul 15;112(2):415-25. Epub 2008 May 1. link to original article contains dosing details in manuscript PubMed

FCR

FCR: Fludarabine, Cyclophosphamide, Rituximab

Regimen

Study Dates of enrollment Evidence
Khouri et al. 2001 (MDACC ID01-233) 1997-2000 Phase 2

Details are best described in the 2008 update.

Chemotherapy

Targeted therapy

  • Rituximab (Rituxan) 375 mg/m2 IV once on day -13, then 1000 mg/m2 IV once per day on days -6, +1, +8

Immunotherapy

GVHD prophylaxis

  • Antithymocyte globulin, horse ATG (Atgam) by the following donor-based criteria:
    • Matched unrelated donor: 15 mg/kg IV once per day on days -5 to -3
  • Tacrolimus (Prograf) adjusted to level of 5 to 10 ng/mL for 6 months in patients in remission
  • Methotrexate (MTX) by the following donor-based criteria:
    • 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

One course

References

  1. MDACC ID01-233: 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 NCT00048737
    1. 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 dosing details in manuscript link to PMC article PubMed
    2. 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 dosing details in manuscript link to PMC article PubMed

Fludarabine & TBI

Regimen variant #1

Study Dates of enrollment Evidence Comparator Comparative Efficacy Non-relapse mortality
Bornhäuser et al. 2012 (9005-2003) 2004-2009 Phase 3 (E-switch-ic) Cyclophosphamide & TBI Did not meet primary endpoint of NRM

Chemotherapy

Radiotherapy

Immunotherapy

One course


Regimen variant #2, low-dose TBI

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Sorror et al. 2005 1997-2003 Phase 2
Gyukocza et al. 2010 1998-2008 Non-randomized
Maris et al. 2003 2000-2001 Phase 2
Björkstrand et al. 2011 (EBMT-NMAM2000) 2001-2005 Non-randomized part of RCT
Kornblit et al. 2013 (FHCRC 1813.00) 2003-2011 Phase 3 (E-esc) Low-dose TBI Might have superior OS36 (primary endpoint)

Details are best described in Maris et al. 2003.

Chemotherapy

Radiotherapy

Immunotherapy

GVHD prophylaxis

  • Cyclosporine 6.25 mg/kg PO twice per day starting 4 to 6 hours after transplant, tapered at day 100 over 80 days (if no GVHD)
  • Mycophenolate mofetil (CellCept) 15 mg/kg PO twice per day starting 4 to 6 hours after transplant, tapered at day 40 over 56 days (if no GVHD)

One course

References

  1. 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 dosing details in manuscript PubMed
  2. 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 contains dosing details in manuscript PubMed
    1. 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
  3. 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 dosing details in manuscript link to PMC article PubMed
  4. EBMT-NMAM2000: 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 contains dosing details in abstract PubMed
    1. 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
  5. 9005-2003: Bornhäuser M, Kienast J, Trenschel R, Burchert A, Hegenbart U, Stadler M, Baurmann H, Schäfer-Eckart K, Holler E, Kröger N, Schmid C, Einsele H, Kiehl MG, Hiddemann W, Schwerdtfeger R, Buchholz S, Dreger P, Neubauer A, Berdel WE, Ehninger G, Beelen DW, Schetelig J, Stelljes M. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol. 2012 Oct;13(10):1035-44. Epub 2012 Sep 7. link to original article contains dosing details in manuscript PubMed NCT00150878
  6. FHCRC 1813.00: Kornblit B, Maloney DG, Storb R, Storek J, Hari P, Vucinic V, Maziarz RT, Chauncey TR, Pulsipher MA, Bruno B, Petersen FB, Bethge WA, Hübel K, Bouvier ME, Fukuda T, Storer BE, Sandmaier BM. Fludarabine and 2-Gy TBI is superior to 200 cGy TBI as conditioning for HLA-matched related hematopoietic cell transplantation: a phase III randomized trial. Biol Blood Marrow Transplant. 2013 Sep;19(9):1340-7. Epub 2013 Jun 11. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00075478

Fludarabine, Cyclophosphamide, TBI for dUCB or haploidentical transplant

dUCB: double Umbilical Cord Blood

Regimen variant #1, dUCB transplantation

Study Dates of enrollment Evidence
Brunstein et al. 2011 (BMT CTN 0604) 2009-01 to 2010-03 Phase 2

Chemotherapy

Radiotherapy

Immunotherapy

Supportive therapy

  • 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/μL for 3 consecutive days

GVHD prophylaxis

  • Mycophenolate mofetil (CellCept) by the following weight-based criteria:
    • More than 50 kg: 1000 mg (route not specified) every 8 hours, starting on day -3 "and continuing until day +30 or 7 days after engraftment, whichever was later"
    • Less than 50 kg: 15 mg/kg (route not specified) every 8 hours, starting on day -3 "and continuing until day +30 or 7 days after engraftment, whichever was later"
  • Cyclosporine (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.

One course


Regimen variant #2, Haploidentical

Study Dates of enrollment Evidence
Brunstein et al. 2011 (BMT CTN 0603) 2009-01 to 2010-03 Phase 2

Chemotherapy

Radiotherapy

Immunotherapy

Supportive therapy

  • 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/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 & +4, started 60 to 72 hours after marrow infusion
  • Mycophenolate mofetil (CellCept) 15 mg/kg (maximum daily dose of 3000 mg; route not specified) every 8 hours, 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

One course

References

  1. BMT CTN 0603: 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; BMT CTN. 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. Epub 2011 Apr 28. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00849147
  2. BMT CTN 0604: 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; BMT CTN. 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. Epub 2011 Apr 28. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00864227
  3. BMT CTN 1101: Fuchs EJ, O'Donnell PV, Eapen M, Logan B, Antin JH, Dawson P, Devine S, Horowitz MM, Horwitz ME, Karanes C, Leifer E, Magenau JM, McGuirk JP, Morris LE, Rezvani AR, Jones RJ, Brunstein CG. Double unrelated umbilical cord blood vs HLA-haploidentical bone marrow transplantation: the BMT CTN 1101 trial. Blood. 2021 Jan 21;137(3):420-428. link to original article link to PMC article PubMed NCT01597778
    1. QoL analysis: El Jurdi N, Martens MJ, Brunstein CG, O'Donnell P, Lee SJ, D'Souza A, Logan B, Hong S, Singh AK, Sandhu K, Shapiro RM, Horowitz MM, Hamilton BK. Health-Related Quality of Life in Double Umbilical Cord Blood versus Haploidentical Marrow Transplantation: A Quality of Life Analysis Report of BMT CTN 1101. Transplant Cell Ther. 2023 Jul;29(7):467.e1-467.e5. Epub 2023 Apr 22. link to original article link to PMC article PubMed

Fludarabine & Melphalan

Flu-Mel: Fludarabine & Melphalan

Regimen variant #1, 90/140

Study Dates of enrollment Evidence Comparator Comparative Efficacy
de Masson et al. 2023 (CUTALLO) 2016-06-01 to 2022-03-03 Propensity score analysis (E-esc) No transplant Superior PFS (primary endpoint)
Median PFS: 9 vs 3 mo
(HR 0.38, 95% CI 0.21-0.69)

Diseases Studied: Cutaneous T-cell lymphoma

Chemotherapy

Immunotherapy

GVHD prophylaxis

  • Cyclosporine started on day -1, tapered on day +90 if no GVHD
  • Methotrexate (MTX) 15 mg/m2 IV once on day +1, then 10 mg/m2 IV once per day on days +3, +6, +11

One course


Regimen variant #2, 132/140

Study Dates of enrollment Evidence
Anderlini et al. 2008 2001-2005 Phase 2

Diseases Studied: Classical Hodgkin lymphoma

Chemotherapy

Immunotherapy

GVHD prophylaxis

  • ATG (type not specified) by the following donor-based criteria:
    • Matched unrelated donor: 2 mg/kg IV once per day on days -4 to -2
  • Tacrolimus (Prograf) IV starting on day -2, dosed to achieve serum levels 4 to 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)

One course


Regimen variant #3, 150/140

Study Dates of enrollment Evidence
Alvarez et al. 2006 1999-06 to 2004-01 Prospective
Sureda et al. 2011 (HDR-ALLO) NR Phase 2

Diseases Studied: Classical Hodgkin lymphoma
Note: Alvarez et al. 2006 began CsA on day -1 and did not give day +11 MTX.

Chemotherapy

Immunotherapy

GVHD prophylaxis

  • Recipients of stem cells from matched unrelated donors received:
  • Cyclosporine starting on day -2 at 1.5 mg/kg IV twice per day
    • 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 +150 (Alvarez et al. 2006) or +180 (HDR-ALLO).
  • Methotrexate (MTX) 10 mg/m2 IV once per day on days +1, +3, +6, +11

One course


Regimen variant #4, 150/40, with alemtuzumab

Study Evidence
Peggs et al. 2005 Non-randomized

Chemotherapy

Immunotherapy

GVHD prophylaxis

One course

References

  1. Peggs KS, Hunter A, Chopra R, Parker A, Mahendra P, Milligan D, Craddock C, Pettengell R, Dogan A, Thomson KJ, Morris EC, Hale G, Waldmann H, Goldstone AH, Linch DC, Mackinnon S. Clinical evidence of a graft-versus-Hodgkin's-lymphoma effect after reduced-intensity allogeneic transplantation. Lancet. 2005 Jun 4-10;365(9475):1934-41. link to original article contains dosing details in manuscript PubMed
  2. 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 dosing details in manuscript PubMed
  3. 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 MD Anderson Cancer Center experience. Haematologica. 2008 Feb;93(2):257-64. Epub 2008 Jan 26. link to original article contains dosing details in manuscript link to PMC article PubMed
  4. HDR-ALLO: 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; GEL/TAMO. 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 dosing details in abstract link to PMC article PubMed
  5. CUTALLO: de Masson A, Beylot-Barry M, Ram-Wolff C, Mear JB, Dalle S, d'Incan M, Ingen-Housz-Oro S, Orvain C, Abraham J, Dereure O, Charbonnier A, Cornillon J, Longvert C, Barete S, Boulinguez S, Wierzbicka-Hainaut E, Aubin F, Rubio MT, Bernard M, Schmidt-Tanguy A, Houot R, Pham-Ledard A, Michonneau D, Brice P, Labussière-Wallet H, Bouaziz JD, Grange F, Moins-Teisserenc H, Jondeau K, Michel L, Mourah S, Battistella M, Daguindau E, Loschi M, Picard A, Franck N, Maillard N, Huynh A, Nguyen S, Marçais A, Chaby G, Ceballos P, Le Corre Y, Maury S, Bay JO, Adamski H, Bachy E, Forcade E, Socié G, Bagot M, Chevret S, Peffault de Latour R; CUTALLO Investigators; Groupe Français d'Etude des Lymphomes Cutanés; Société Française de Greffe de Moëlle et Thérapie Cellulaire. Allogeneic transplantation in advanced cutaneous T-cell lymphomas (CUTALLO): a propensity score matched controlled prospective study. Lancet. 2023 Jun 10;401(10392):1941-1950. Epub 2023 Apr 24. link to original article contains dosing details in supplement PubMed NCT02520908

Low-dose TBI

TBI: Total Body Irradiation

Regimen

Study Evidence
Gyukocza et al. 2010 Non-randomized

Radiotherapy

Immunotherapy

GVHD prophylaxis

One course

References

  1. 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 dosing details in manuscript link to PMC article PubMed

TLI

TLI: Total Lymphocyte Irradiation

Regimen

Study Dates of enrollment Evidence
Lowsky et al. 2005 2001-12-28 to 2004-12-01 Non-randomized
Kohrt et al. 2009 (BMT153) 2001-12-28 to 2007-09-06 Non-randomized

Note: the schedule for TLI in BMT153 is slightly different, although the manuscript states that the protocol from Lowsky et al. 2005 was followed. See paper for details.

Radiotherapy

  • TLI 800 cGy once per day on days -11 to -1 (10 fractions)

GVHD prophylaxis

Immunotherapy

One course

References

  1. 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 contains dosing details in manuscript PubMed
  2. BMT153: 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. Epub 2009 May 7. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00185640

(90)YFC

(90)YFC: Ibritumomab tiuxetan, Fludarabine, Cyclophosphamide

Regimen

Study Dates of enrollment Evidence
Khouri et al. 2001 (MDACC ID01-233) 1997-2000 Phase 2

Note: this regimen is specifically addressed in the 2012 update.

Targeted therapy

Radioconjugate therapy

Chemotherapy

Immunotherapy

GVHD prophylaxis

One course

References

  1. MDACC ID01-233: 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 NCT00048737
    1. 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 dosing details in manuscript link to PMC article PubMed
    2. 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 dosing details in manuscript link to PMC article PubMed
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