Post-transplant cyclophosphamide (PTCy) is being increasingly used as graft-versus-host disease (GVHD) prophylaxis post allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia (AML) transplanted in first complete remission (CR1). However, results may differ in patients transplanted in CR2. We retrospectively evaluated transplant outcomes of adult AML patients transplanted between 2010-2019 from 9-10/10 human leukocyte antigen (HLA)-matched unrelated donor (UD) in CR2. In total, 127 patients were included (median age 45.5 years, 54% male). Median follow-up was 19.2 months. Conditioning was myeloablative (MAC) in 50.4% and the graft source was peripheral blood in 93.7% of the transplants. Incidence of acute (a)GVHD II-IV and III-IV was 26.2% and 9.2%. Two-year total and extensive chronic (c)GVHD were 34.3% and 13.8 %, respectively. Two-year non-relapse mortality (NRM), relapse incidence (RI), leukemia-free survival (LFS), overall survival (OS), and GVHD-free, relapse-free survival (GRFS) were 17.2%, 21.1%, 61.7, %, 65.2%, and 49.3%, respectively. Time from diagnosis to transplant (>18 months) was a favorable prognostic factor for RI, LFS, OS, and GRFS while favorable risk cytogenetics was a positive prognostic factor for OS. The patient's age was a poor prognostic factor for NRM and cGVHD. Finally, the female-to-male combination and reduced intensity conditioning (RIC) were poor and favorable prognostic factors for cGVHD, respectively. We conclude that PTCy is an effective method for GVHD prophylaxis in AML patients undergoing allo-HCT in CR2 from UD.

1st State Pavlov Medical University of St Petersburg Raisa Gorbacheva Memorial Research Institute for Paediatric Oncology Hematology and Transplantation St Petersburg Russia

ALWP of the EBMT Paris office Paris France

Centre Hospitalier Lyon Sud Pavillon Marcel Bérard Service Hematologie Lyon France

CHU de Lille Univ Lille INSERM U1286 Infinite 59000 Lille France

Dél pesti Centrumkórház Országos Hematológiai és Infektológiai Intézet; Dept Haematology and Stem Cell Transplant Albert Budapest Hungary

Department of Bone Marrow Transplantation and Onco Hematology Maria Sklodowska Curie National Research Institute of Oncology Gliwice Branch Gliwice Poland

Deptartment of Hematology; University Medical Center Groningen University of Groningen Groningen The Netherlands

Division of Hematology Sheba Medical Center Tel Hashomer Israel

Hospital Clinic Department of Hematology Institute of Hematology and Oncology Barcelona Spain

Hospital Universitari i Politècnic La Fe Valencia Spain

Institute of Hematology and Blood Transfusion Prague Czech Republic

Medicana International Hospital Istanbul; Bone Marrow Transplant Unit Istanbul Turkey

Ospedale San Raffaele s r l Haematology and BMT Milano Italy

Programme de Transplantation and Therapie Cellulaire Centre de Recherche en Cancérologie de Marseille; Institut Paoli Calmettes Marseille France

Sorbonne University Department of Clinical Hematology and Cellular Therapy Hospital Saint Antoine AP HP INSERM UMRs 938 Paris France

Sorbonne University Department of Haematology Saint Antoine Hospital INSERM UMR 938 Paris France

See more in PubMed

Zeiser R, Blazar BR, Acute Graft-versus-Host Disease -. Biologic Process, Prevention, and Therapy. N Engl J Med. 2017;377:2167–79. PubMed DOI PMC

Zeiser R, Blazar BR. Pathophysiology of Chronic Graft-versus-Host Disease and Therapeutic Targets. N Engl J Med. 2017;377:2565–79. PubMed DOI

Tegla C, Choi J, Abdul-Hay M, Cirrone F, Cole K, Al-Homsi AS. Current Status and Future Directions in Graft-Versus-Host Disease Prevention Following Allogeneic Blood and Marrow Transplantation in Adults. Clin Hematol Int. 2020;2:5–12. PubMed DOI PMC

Storb R, Deeg HJ, Whitehead J, Cirrone F, Cole K, Al-Homsi AS. Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia. N Engl J Med. 1986;314:729–35. PubMed DOI

Storb R, Deeg HJ, Pepe M, Appelbaum F, Anasetti C, Beatty P, et al. Methotrexate and cyclosporine versus cyclosporine alone for prophylaxis of graft-versus-host disease in patients given HLA-identical marrow grafts for leukemia: long-term follow-up of a controlled trial. Blood 1989;73:1729–1734.9. PubMed DOI

Luznik L, O’Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transpl. 2008;14:641–50. https://doi.org/10.1016/j.bbmt.2008.03.005 . DOI

Kasamon YL, Luznik L, Leffell MS, Kowalski J, Tsai HL, Bolaños-Meade J, et al. Nonmyeloablative HLA-haploidentical bone marrow transplantation with high-dose posttransplantation cyclophosphamide: effect of HLA disparity on outcome. Biol Blood Marrow Transpl. 2010;16:482–9. https://doi.org/10.1016/j.bbmt.2009.11.011 . DOI

Saliba RM, Majid AA, Pidala J, Arora M, Spellman SR, Hemmer MT, et al. Characteristics of Graft-versus-Host Disease (GvHD) after Post-Transplant Cyclophosphamide versus Conventional GvHD Prophylaxis. Transpl Cell Ther. 2022;16:S2666–636701476-2. https://doi.org/10.1016/j.jtct.2022.07.013 . DOI

Mayumi H, Umesue M, Nomoto K. Cyclophosphamide-induced immunological tolerance: an overview. Immunobiology. 1996;195:129–39. PubMed DOI

Raiola AM, Dominietto A, Ghiso A, Di Grazia C, Lamparelli T, Gualandi F, et al. Unmanipulated haploidentical bone marrow transplantation and posttransplantation cyclophosphamide for hematologic malignancies after myeloablative conditioning. Biol Blood Marrow Tran. 2013;19:117–22.11. DOI

Jones RJ, Barber JP, Vala MS, Collector MI, Kaufmann SH, Ludeman SM, et al. Assessment of aldehyde dehydrogenase in viable cells. Blood. 1995;85:2742–6. PubMed DOI

Russo A, Oliveira G, Berglund S, Greco R, Gambacorta V, Cieri N, et al. NK cell recovery after haploidentical HSCT with pos ttransplant cyclophosphamide: dynamics and clinical implications. Blood. 2018;131:247–62. PubMed DOI PMC

Rambaldi B, Kim HT, Reynolds C, Chamling Rai S, Arihara Y, Kubo T, et al. Impaired T- and NK-cell reconstitution after haploidentical HCT with post-transplant cyclophosphamide. Blood Adv. 2021;5:352–64. PubMed DOI PMC

Ruggeri A, Labopin M, Bacigalupo A, Afanasyev B, Cornelissen JJ, Elmaagacli A, et al. Post-transplant cyclophosphamide for graft-versus-host disease prophylaxis in HLA matched sibling or matched unrelated donor transplant for patients with acute leukemia, on behalf of ALWP-EBMT. J Hematol Oncol. 2018;11:40. PubMed DOI PMC

Lorentino F, Labopin M, Ciceri F, Vago L, Fleischhauer K, Afanasyev B, et al. Acute Leukemia Working Party (ALWP) and Cellular Therapy and Immunobiology Working Party (CTIWP) of the European Society for Blood and Marrow Transplantation (EBMT). Post-transplantation cyclophosphamide GvHD prophylaxis after hematopoietic stem cell transplantation from 9/10 or 10/10 HLA-matched unrelated donors for acute leukemia. Leukemia. 2021;35:585–94. PubMed DOI

Brissot E, Labopin M, Moiseev I, Cornelissen JJ, Meijer E, Van Gorkom G, et al. Post-transplant cyclophosphamide versus antithymocyte globulin in patients with acute myeloid leukemia in first complete remission undergoing allogeneic stem cell transplantation from 10/10 HLA-matched unrelated donors. J Hematol Oncol. 2020;13:87. PubMed DOI PMC

Battipaglia G, Labopin M, Hamladji RM, Blaise D, Chevallier P, Brissot E, et al. Post-Transplant cyclophosphamide versus antithymocyte globulin patients Acute myeloid Leuk undergoing allogeneic stem cell Transplant HLA-identical sibling donors: A retrospective Anal Acute Leuk Working Part Eur Soc Blood Marrow Transplant Cancer. 2021;127:209–18. 5

Battipaglia G, Galimard JE, Labopin M, Raiola AM, Blaise D, Ruggeri A, et al. Post-transplant cyclophosphamide in one-antigen mismatched unrelated donor transplantation versus haploidentical transplantation in acute myeloid leukemia: a study from the Acute Leukemia WorkingParty of the EBMT. Bone Marrow Transpl. 2022;57:562–71. DOI

Sanz J, Galimard JE, Labopin M, Afanasyev B, Angelucci E, Ciceri F, et al. Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT). 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;13:46. PubMed DOI PMC

Gilleece MH, Labopin M, Savani BN, Yakoub-Agha I, Socié G, Gedde-Dahl T, et al. Allogeneic haemopoietic transplantation for acute myeloid leukaemia in second complete remission: a registry report by the Acute Leukaemia Working Party of the EBMT. Leukemia. 2020;34:87–99. PubMed DOI

Gilleece MH, Shimoni A, Labopin M, Robinson S, Beelen D, Socié G, et al. Measurable residual disease status and outcome of transplant in acute myeloid leukemia in second complete remission: a study by the acute leukemia working party of the EBMT. Blood Cancer J. 2021;11:88. PubMed DOI PMC

Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transpl. 2009;15:1628–33. DOI

Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transpl. 1995;15:825–8.

Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE, et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med. 1980;69:204–17. PubMed DOI

Kanate AS, Nagler A, Savani B. Summary of scientific and statistical methods, study endpoints and definitions for observational and registry-based studies in hematopoietic cell transplantation. Clin Hematol Int. 2019;2:2–4. PubMed DOI PMC

Ruggeri A, Labopin M, Ciceri F, Mohty M, Nagler A. Definition of GvHD-free, relapse-free survival for registry-based studies: an ALWP-EBMT analysis on patients with AML in remission. Bone Marrow Transpl. 2016;51:610–1. DOI

R Core Team. R: a language and environment for statistical computing. R Foundation for Statistical Computing; 2020. https://www.R-project.org/

Wachsmuth LP, Patterson MT, Eckhaus MA, Venzon DJ, Gress RE, Kanakry CG. Post-transplantation cyclophosphamide prevents graft-versus-host disease by inducing alloreactive T cell dysfunction and suppression. J Clin Invest. 2019;129:2357–73. PubMed DOI PMC

Rimando JC, McCurdy SR, Luznik. How We Prevent GVHD in High Risk Patients: Post-Transplant Cyclophosphamide and Beyond.L. Blood. 2022 Apr: blood.2021015129. https://doi.org/10.1182/blood.2021015129

Mussetti A, Paviglianiti A, Parody R, Sureda A. Is Post-Transplant Cyclophosphamide the New Methotrexate? A J Clin Med. 2021;10:3548 https://doi.org/10.3390/jcm10163548 . PubMed DOI

Jentzsch M, Bischof L, Backhaus D, Brauer D, Schulz J, Franke GN, et al. Impact of MRD status in patients with AML undergoing allogeneic stem cell transplantation in the first vs the second remission. Blood Adv. 2022;6(Aug):4570–80. PubMed DOI PMC

Shouval R, Fein JA, Labopin M, Kröger N, Duarte RF, Bader P, et al. Outcomes of allogeneic haematopoietic stem cell transplantation from HLA-matched and alternative donors: a European Society for Blood and Marrow Transplantation registry retrospective analysis. Lancet Haematol. 2019;6:e573–e584. PubMed DOI

Nagler A, Labopin M, Craddock C, Socié G, Yakoub-Agha I, Gedde-Dahl T, et al. Cytogenetic risk classification maintains its prognostic significance in transplanted FLT3-ITD mutated acute myeloid leukemia patients: On behalf of the acute leukemia working party/European society of blood and marrow transplantation. Am J Hematol. 2022;97(Mar):274–82. PubMed DOI

Battipaglia G, Labopin M, Kröger N, Vitek A, Afanasyev B, Hilgendorf I, et al. Posttransplant cyclophosphamide vs antithymocyte globulin in HLA-mismatched unrelated donor transplantation. Blood 2019;134:892–9. PubMed DOI