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Review Article

Current status of conditioning regimens in haploidentical hematopoietic cell transplantation

ORCID Icon & ORCID Icon
Article: 2332866 | Received 11 Dec 2023, Accepted 15 Mar 2024, Published online: 21 Mar 2024

References

  • Copelan EA. Hematopoietic stem-cell transplantation. N Engl J Med. 2006;354(17):1813–1826. doi:10.1056/NEJMra052638
  • Yanada M. The evolving concept of indications for allogeneic hematopoietic cell transplantation during first complete remission of acute myeloid leukemia. Bone Marrow Transplant. 2021;56(6):1257–1265. doi:10.1038/s41409-021-01247-4
  • Yanada M, Harada K, Shimomura Y, et al. Conditioning regimens for allogeneic hematopoietic cell transplantation in acute myeloid leukemia: Real-world data from the Japanese registry studies. Front Oncol. 2022;12:1050633. doi:10.3389/fonc.2022.1050633
  • Pingali SR, Champlin RE. Pushing the envelope-nonmyeloablative and reduced intensity preparative regimens for allogeneic hematopoietic transplantation. Bone Marrow Transplant. 2015;50(9):1157–1167. doi:10.1038/bmt.2015.61
  • Sengsayadeth S, Savani BN, Blaise D, et al. Reduced intensity conditioning allogeneic hematopoietic cell transplantation for adult acute myeloid leukemia in complete remission - a review from the Acute Leukemia Working Party of the EBMT. Haematologica. 2015;100(7):859–869. doi:10.3324/haematol.2015.123331
  • Holtan SG, Versluis J, Weisdorf DJ, et al. Optimizing donor choice and GVHD prophylaxis in allogeneic hematopoietic cell transplantation. J Clin Oncol. 2021;39(5):373–385. doi:10.1200/JCO.20.01771
  • Yanada M, Takami A, Yamasaki S, et al. Allogeneic hematopoietic cell transplantation for adults with acute myeloid leukemia conducted in Japan during the past quarter century. Ann Hematol. 2020;99(6):1351–1360. doi:10.1007/s00277-020-04051-0
  • D'Souza A, Fretham C, Lee SJ, et al. Current use of and trends in hematopoietic cell transplantation in the United States. Biol Blood Marrow Transplant. 2020;26(8):e177–e182. doi:10.1016/j.bbmt.2020.04.013
  • Passweg JR, Baldomero H, Chabannon C, et al. Hematopoietic cell transplantation and cellular therapy survey of the EBMT: monitoring of activities and trends over 30 years. Bone Marrow Transplant. 2021;56(7):1651–1664. doi:10.1038/s41409-021-01227-8
  • Lee CJ, Savani BN, Mohty M, et al. Haploidentical hematopoietic cell transplantation for adult acute myeloid leukemia: a position statement from the Acute Leukemia Working Party of the European society for blood and marrow transplantation. Haematologica. 2017;102(11):1810–1822. doi:10.3324/haematol.2017.176107
  • Anasetti C, Amos D, Beatty PG, et al. Effect of HLA compatibility on engraftment of bone marrow transplants in patients with leukemia or lymphoma. N Engl J Med. 1989;320(4):197–204. doi:10.1056/NEJM198901263200401
  • Luznik L, O'Donnell PV, Symons HJ, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008;14(6):641–650. doi:10.1016/j.bbmt.2008.03.005
  • Wang Y, Liu DH, Xu LP, et al. Superior graft-versus-leukemia effect associated with transplantation of haploidentical compared with HLA-identical sibling donor grafts for high-risk acute leukemia: an historic comparison. Biol Blood Marrow Transplant. 2011;17(6):821–830. doi:10.1016/j.bbmt.2010.08.023
  • Ciurea SO, Zhang MJ, Bacigalupo AA, et al. Haploidentical transplant with posttransplant cyclophosphamide vs matched unrelated donor transplant for acute myeloid leukemia. Blood. 2015;126(8):1033–1040. doi:10.1182/blood-2015-04-639831
  • Brissot E, Labopin M, Ehninger G, et al. Haploidentical versus unrelated allogeneic stem cell transplantation for relapsed/refractory acute myeloid leukemia: a report on 1578 patients from the Acute Leukemia Working Party of the EBMT. Haematologica. 2019;104(3):524–532. doi:10.3324/haematol.2017.187450
  • Rashidi A, Hamadani M, Zhang MJ, et al. Outcomes of haploidentical vs matched sibling transplantation for acute myeloid leukemia in first complete remission. Blood Adv. 2019;3(12):1826–1836. doi:10.1182/bloodadvances.2019000050
  • Sanz J, Galimard JE, Labopin M, et al. Post-transplant cyclophosphamide after matched sibling, unrelated and haploidentical donor transplants in patients with acute myeloid leukemia: a comparative study of the ALWP EBMT. J Hematol Oncol. 2020;13(1):46. doi:10.1186/s13045-020-00882-6
  • Fuchs EJ, O'Donnell PV, Eapen M, et al. Double unrelated umbilical cord blood vs HLA-haploidentical bone marrow transplantation: the BMT CTN 1101 trial. Blood. 2021;137(3):420–428. doi:10.1182/blood.2020007535
  • Ruggeri A, Galimard JE, Labopin M, et al. Comparison of outcomes after unrelated double-unit cord blood and haploidentical peripheral blood stem cell transplantation in adults with acute myelogenous leukemia: a study on behalf of eurocord and the acute leukemia working party of the European society for blood and marrow transplantation. Transplant Cell Ther. 2022;28(10):710 e710–710 e711. doi:10.1016/j.jtct.2022.07.006
  • Bacigalupo A, Ballen K, Rizzo D, et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant. 2009;15(12):1628–1633. doi:10.1016/j.bbmt.2009.07.004
  • Giralt S, Ballen K, Rizzo D, et al. Reduced-intensity conditioning regimen workshop: defining the dose spectrum. Report of a workshop convened by the center for international blood and marrow transplant research. Biol Blood Marrow Transplant. 2009;15(3):367–369. doi:10.1016/j.bbmt.2008.12.497
  • Scott BL, Pasquini MC, Logan BR, et al. Myeloablative versus reduced-intensity hematopoietic cell transplantation for acute myeloid leukemia and myelodysplastic syndromes. J Clin Oncol. 2017;35(11):1154–1161. doi:10.1200/JCO.2016.70.7091
  • Bornhauser M, Kienast J, Trenschel R, et al. 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;13(10):1035–1044. doi:10.1016/S1470-2045(12)70349-2
  • Kroger N, Iacobelli S, Franke GN, et al. 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;35(19):2157–2164. doi:10.1200/JCO.2016.70.7349
  • Craddock C, Jackson A, Loke J, et al. Augmented reduced-intensity regimen does not improve postallogeneic transplant outcomes in acute myeloid leukemia. J Clin Oncol. 2021;39(7):768–778. doi:10.1200/JCO.20.02308
  • Solomon SR, Sizemore CA, Sanacore M, et al. Haploidentical transplantation using T cell replete peripheral blood stem cells and myeloablative conditioning in patients with high-risk hematologic malignancies who lack conventional donors is well tolerated and produces excellent relapse-free survival: results of a prospective phase II trial. Biol Blood Marrow Transplant. 2012;18(12):1859–1866. doi:10.1016/j.bbmt.2012.06.019
  • Solomon SR, Solh M, Zhang X, et al. Fludarabine and total-body irradiation conditioning before ablative haploidentical transplantation: long-term safety and efficacy. Biol Blood Marrow Transplant. 2019;25(11):2211–2216. doi:10.1016/j.bbmt.2019.06.017
  • Dulery R, Goudet C, Mannina D, et al. Reduced post-transplant cyclophosphamide doses in haploidentical hematopoietic cell transplantation for elderly patients with hematological malignancies. Bone Marrow Transplant. 2023;58(4):386–392. doi:10.1038/s41409-022-01908-y
  • Fuji S, Sugita J, Najima Y, et al. Low- versus standard-dose post-transplant cyclophosphamide as GVHD prophylaxis for haploidentical transplantation. Br J Haematol. 2023 Dec 6. Online ahead of print.
  • O'Donnell PV, Luznik L, Jones RJ, et al. Nonmyeloablative bone marrow transplantation from partially HLA-mismatched related donors using posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2002;8(7):377–386. doi:10.1053/bbmt.2002.v8.pm12171484
  • Gottdiener JS, Appelbaum FR, Ferrans VJ, et al. Cardiotoxicity associated with high-dose cyclophosphamide therapy. Arch Intern Med. 1981;141(6):758–763. doi:10.1001/archinte.1981.00340060066015
  • Braverman AC, Antin JH, Plappert MT, et al. Cyclophosphamide cardiotoxicity in bone marrow transplantation: a prospective evaluation of new dosing regimens. J Clin Oncol. 1991;9(7):1215–1223. doi:10.1200/JCO.1991.9.7.1215
  • Ishida S, Doki N, Shingai N, et al. The clinical features of fatal cyclophosphamide-induced cardiotoxicity in a conditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Ann Hematol. 2016;95(7):1145–1150. doi:10.1007/s00277-016-2654-6
  • Dulery R, Mohty R, Labopin M, et al. Early cardiac toxicity associated with post-transplant cyclophosphamide in allogeneic stem cell transplantation. JACC CardioOncol. 2021;3(2):250–259. doi:10.1016/j.jaccao.2021.02.011
  • Yeh J, Whited L, Saliba RM, et al. Cardiac toxicity after matched allogeneic hematopoietic cell transplant in the posttransplant cyclophosphamide era. Blood Adv. 2021;5(24):5599–5607. doi:10.1182/bloodadvances.2021004846
  • Ruggeri A, Labopin M, Angelucci E, et al. Prognostic factors for neutrophil engraftment after haploidentical cell transplantation with PT-Cy in patients with acute myeloid leukemia in complete remission, on behalf of the ALWP-EBMT. Bone Marrow Transplant. 2021;56(8):1842–1849. doi:10.1038/s41409-021-01248-3
  • Shah N, Cioccio J, Rakszawski K, et al. Low-dose total body irradiation promotes T-cells donor chimerism in reduced-intensity/non-myeloablative allogeneic stem cell transplant with post-transplant cyclophosphamide. Leuk Res. 2022;123:106969. doi:10.1016/j.leukres.2022.106969
  • DeZern AE, Zahurak M, Symons HJ, et al. Alternative donor BMT with posttransplant cyclophosphamide as initial therapy for acquired severe aplastic anemia. Blood. 2023;141(25):3031–3038.
  • Sugita J, Kagaya Y, Miyamoto T, et al. Myeloablative and reduced-intensity conditioning in HLA-haploidentical peripheral blood stem cell transplantation using post-transplant cyclophosphamide. Bone Marrow Transplant. 2019;54(3):432–441. doi:10.1038/s41409-018-0279-1
  • Sugita J, Kamimura T, Ishikawa T, et al. Reduced dose of posttransplant cyclophosphamide in HLA-haploidentical peripheral blood stem cell transplantation. Bone Marrow Transplant. 2021;56(3):596–604. doi:10.1038/s41409-020-01065-0
  • Imus PH, Tsai HL, Luznik L, et al. Haploidentical transplantation using posttransplant cyclophosphamide as GVHD prophylaxis in patients over age 70. Blood Adv. 2019;3(17):2608–2616. doi:10.1182/bloodadvances.2019000155
  • Harbi S, Brac de la Perriere L, Bouchacourt B, et al. Peripheral blood haploidentical hematopoietic cell transplantation for patients aged 70 years and over with acute myeloid leukemia or high-risk myelodysplastic syndrome. Bone Marrow Transplant. 2024;59(1):101–106. doi:10.1038/s41409-023-02134-w
  • Dulery R, Malard F, Brissot E, et al. Reduced post-transplant cyclophosphamide dose with antithymocyte globulin in peripheral blood stem cell haploidentical transplantation. Bone Marrow Transplant. 2023;58(11):1215–1222. doi:10.1038/s41409-023-02085-2
  • Chiusolo P, Bug G, Olivieri A, et al. A modified post-transplant cyclophosphamide regimen, for unmanipulated haploidentical marrow transplantation, in acute myeloid leukemia: a multicenter study. Biol Blood Marrow Transplant. 2018;24(6):1243–1249. doi:10.1016/j.bbmt.2018.01.031
  • Symons HJ, Zahurak M, Cao Y, et al. Myeloablative haploidentical BMT with posttransplant cyclophosphamide for hematologic malignancies in children and adults. Blood Adv. 2020;4(16):3913–3925. doi:10.1182/bloodadvances.2020001648
  • Cieri N, Greco R, Crucitti L, et al. Post-transplantation cyclophosphamide and sirolimus after haploidentical hematopoietic stem cell transplantation using a treosulfan-based myeloablative conditioning and peripheral blood stem cells. Biol Blood Marrow Transplant. 2015;21(8):1506–1514. doi:10.1016/j.bbmt.2015.04.025
  • Dholaria B, Labopin M, Angelucci E, et al. Impact of total body irradiation- vs chemotherapy-based myeloablative conditioning on outcomes of haploidentical hematopoietic cell transplantation for acute myelogenous leukemia. Am J Hematol. 2020;95(10):1200–1208. doi:10.1002/ajh.25934
  • Dholaria B, Labopin M, Angelucci E, et al. Improved outcomes of haploidentical hematopoietic cell transplantation with total body irradiation-based myeloablative conditioning in acute lymphoblastic leukemia. Transplant Cell Ther. 2021;27(2):171 e171–171 e178. doi:10.1016/j.jtct.2020.10.008
  • Swoboda R, Labopin M, Giebel S, et al. Total body irradiation plus fludarabine versus thiotepa, busulfan plus fludarabine as a myeloablative conditioning for adults with acute lymphoblastic leukemia treated with haploidentical hematopoietic cell transplantation. A study by the Acute Leukemia Working Party of the EBMT. Bone Marrow Transplant. 2022;57(3):399–406. doi:10.1038/s41409-021-01550-0
  • Danylesko I, Shimoni A, Nagler A. Treosulfan-based conditioning before hematopoietic SCT: more than a BU look-alike. Bone Marrow Transplant. 2012;47(1):5–14. doi:10.1038/bmt.2011.88
  • Saraceni F, Labopin M, Raiola AM, et al. Thiotepa-busulfan-fludarabine Compared to treosulfan-based conditioning for haploidentical transplant with posttransplant cyclophosphamide in patients with acute myeloid leukemia in remission: a study from the acute leukemia working party of the EBMT. Hemasphere. 2023;7(10):e952. doi:10.1097/HS9.0000000000000952
  • Ling Y, Xuan L, Xu N, et al. 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;41(29):4632–4642. doi:10.1200/JCO.23.00101
  • Burroughs LM, O'Donnell PV, Sandmaier BM, et al. Comparison of outcomes of HLA-matched related, unrelated, or HLA-haploidentical related hematopoietic cell transplantation following nonmyeloablative conditioning for relapsed or refractory Hodgkin lymphoma. Biol Blood Marrow Transplant. 2008;14(11):1279–1287. doi:10.1016/j.bbmt.2008.08.014
  • Kasamon YL, Bolanos-Meade J, Prince GT, et al. Outcomes of nonmyeloablative HLA-haploidentical blood or marrow transplantation with high-dose post-transplantation cyclophosphamide in older adults. J Clin Oncol. 2015;33(28):3152–3161. doi:10.1200/JCO.2014.60.4777
  • Brammer JE, Khouri I, Gaballa S, et al. Outcomes of haploidentical stem cell transplantation for lymphoma with melphalan-based conditioning. Biol Blood Marrow Transplant. 2016;22(3):493–498. doi:10.1016/j.bbmt.2015.10.015
  • Ciurea SO, Shah MV, Saliba RM, et al. Haploidentical transplantation for older patients with acute myeloid leukemia and myelodysplastic syndrome. Biol Blood Marrow Transplant. 2018;24(6):1232–1236. doi:10.1016/j.bbmt.2017.09.005
  • Castagna L, Dodero A, Patriarca F, et al. Multicenter phase II study on haploidentical bone marrow transplantation using a reduced-intensity conditioning regimen and posttransplantation cyclophosphamide in patients with poor-prognosis lymphomas. Transplant Cell Ther. 2021;27(4):328 e321–328 e326. doi:10.1016/j.jtct.2021.01.007
  • Tanaka T, Nakamae H, Ito A, et al. A Phase I/II multicenter trial of HLA-haploidentical PBSCT with PTCy for aggressive adult T cell leukemia/lymphoma. Transplant Cell Ther. 2021;27(11):928 e921–928 e927. doi:10.1016/j.jtct.2021.07.010
  • Devillier R, Galimard JE, Labopin M, et al. Reduced intensity versus non-myeloablative conditioning regimen for haploidentical transplantation and post-transplantation cyclophosphamide in complete remission acute myeloid leukemia: a study from the ALWP of the EBMT. Bone Marrow Transplant. 2022;57(9):1421–1427. doi:10.1038/s41409-022-01674-x
  • Al Malki MM, Palmer J, Tsai NC, et al. Total marrow and lymphoid irradiation as conditioning in haploidentical transplant with posttransplant cyclophosphamide. Blood Adv. 2022;6(14):4098–4106. doi:10.1182/bloodadvances.2022007264
  • Spyridonidis A, Labopin M, Savani BN, et al. Redefining and measuring transplant conditioning intensity in current era: a study in acute myeloid leukemia patients. Bone Marrow Transplant. 2020;55(6):1114–1125. doi:10.1038/s41409-020-0803-y
  • Casper J, Knauf W, Kiefer T, et al. Treosulfan and fludarabine: a new toxicity-reduced conditioning regimen for allogeneic hematopoietic stem cell transplantation. Blood. 2004;103(2):725–731. doi:10.1182/blood-2002-11-3615
  • Casper J, Wolff D, Knauf W, et al. Allogeneic hematopoietic stem-cell transplantation in patients with hematologic malignancies after dose-escalated treosulfan/fludarabine conditioning. J Clin Oncol. 2010;28(20):3344–3351. doi:10.1200/JCO.2009.23.3429
  • Ruutu T, Volin L, Beelen DW, et al. Reduced-toxicity conditioning with treosulfan and fludarabine in allogeneic hematopoietic stem cell transplantation for myelodysplastic syndromes: final results of an international prospective phase II trial. Haematologica. 2011;96(9):1344–1350. doi:10.3324/haematol.2011.043810
  • Casper J, Holowiecki J, Trenschel R, et al. Allogeneic hematopoietic SCT in patients with AML following treosulfan/fludarabine conditioning. Bone Marrow Transplant. 2012;47(9):1171–1177. doi:10.1038/bmt.2011.242
  • Lazzari L, Ruggeri A, Lupo Stanghellini MT, et al. Treosulfan-based conditioning regimen prior to allogeneic stem cell transplantation: long-term results from a phase 2 clinical trial. Front Oncol. 2021;11:731478. doi:10.3389/fonc.2021.731478
  • Beelen DW, Trenschel R, Stelljes M, et al. 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;7(1):e28–e39. doi:10.1016/S2352-3026(19)30157-7
  • Beelen DW, Stelljes M, Remenyi P, et al. Treosulfan compared with reduced-intensity busulfan improves allogeneic hematopoietic cell transplantation outcomes of older acute myeloid leukemia and myelodysplastic syndrome patients: Final analysis of a prospective randomized trial. Am J Hematol. 2022;97(8):1023–1034. doi:10.1002/ajh.26620
  • Chichra A, Nayak L, Kothari R, et al. Fludarabine melphalan versus fludarabine treosulfan for reduced intensity conditioning regimen in allogeneic hematopoietic stem cell transplantation: a retrospective analysis. Int J Hematol. 2024;119(1):71–79. doi:10.1007/s12185-023-03674-z
  • Paix A, Antoni D, Waissi W, et al. Total body irradiation in allogeneic bone marrow transplantation conditioning regimens: A review. Crit Rev Oncol Hematol. 2018;123:138–148. doi:10.1016/j.critrevonc.2018.01.011
  • Huselton E, Slade M, Trinkaus KM, et al. Propensity score analysis of conditioning intensity in peripheral blood haploidentical hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2018;24(10):2047–2055. doi:10.1016/j.bbmt.2018.05.024
  • Modi D, Kim S, Deol A, et al. Comparison of myeloablative and reduced intensity conditioning regimens in haploidentical peripheral blood stem cell transplantation. Bone Marrow Transplant. 2021;56(3):741–744. doi:10.1038/s41409-020-01079-8
  • Solomon SR, St Martin A, Shah NN, et al. Myeloablative vs reduced intensity T-cell-replete haploidentical transplantation for hematologic malignancy. Blood Adv. 2019;3(19):2836–2844. doi:10.1182/bloodadvances.2019000627
  • Santoro N, Labopin M, Ciceri F, et al. Impact of conditioning intensity on outcomes of haploidentical stem cell transplantation for patients with acute myeloid leukemia 45 years of age and over. Cancer. 2019;125(9):1499–1506. doi:10.1002/cncr.31941
  • Arcuri LJ, Hamerschlak N, Rocha V, et al. Outcomes after haploidentical hematopoietic cell transplantation with post-transplantation cyclophosphamide: a systematic review and meta-analysis comparing myeloablative with reduced-intensity conditioning regimens and bone marrow with peripheral blood stem cell grafts. Transplant Cell Ther. 2021;27(9):782 e781–782 e787. doi:10.1016/j.jtct.2021.06.011
  • Bejanyan N, Weisdorf DJ, Logan BR, et al. Survival of patients with acute myeloid leukemia relapsing after allogeneic hematopoietic cell transplantation: a center for international blood and marrow transplant research study. Biol Blood Marrow Transplant. 2015;21(3):454–459. doi:10.1016/j.bbmt.2014.11.007
  • Yanada M, Konuma T, Yamasaki S, et al. Relapse of acute myeloid leukemia after allogeneic hematopoietic cell transplantation: clinical features and outcomes. Bone Marrow Transplant. 2021;56(5):1126–1133. doi:10.1038/s41409-020-01163-z