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Impact of post-transplant cyclophosphamide (PTCy)-based prophylaxis in matched sibling donor allogeneic haematopoietic cell transplantation for patients with myelodysplastic syndrome: a retrospective study on behalf of the Chronic Malignancies Working Party of the EBMT

Bone Marrow Transplantation volume 59, pages 479–488 (2024)Cite this article

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Abstract

We retrospectively compared outcomes of 404 MDS patients undergoing 1st matched sibling donor allo-HCT receiving either PTCy-based (n = 66) or other “conventional prophylaxis” (n = 338; mostly calcineurin inhibitor + methotrexate or MMF). Baseline characteristics were balanced, except for higher use of myeloablative regimens in the PTCy group (52.3% vs. 38.2%, p = 0.047). Incidences of neutrophil (Day +28: 89% vs. 97%, p = 0.011) and platelet (Day +100: 89% vs. 97%, p < 0.001) engraftment were lower for PTCy-based. Day +100 cumulative incidences of grade II–IV and III–IV aGVHD, and 5-year CI of extensive cGVHD were 32%, 18% and 18% for PTCy-based and 25% (p = 0.3), 13% (p = 0.4) and 31% (p = 0.09) for the conventional cohort. Five-year OS (51% vs. 52%, p = 0.6) and GRFS (33% vs. 25%, p = 0.6) were similar between groups. Patients receiving PTCy had a trend to a lower cumulative incidence of relapse (20% vs. 33%, p = 0.06), not confirmed on multivariable analysis (p = 0.3). Although higher NRM rates were observed in patients receiving PTCy (32% vs. 21%, p = 0.02) on univariate analysis, this was not confirmed on multivariate analysis (HR 1.46, p = 0.18), and there was no resultant effect on OS (HR 1.20, p = 0.5). Based on these data, PTCy prophylaxis appears to be an attractive option for patients with MDS undergoing MSD allo-HCT.

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Fig. 1: Incidences of GVHD according to GVHD prophylaxis.
Fig. 2: Post-transplant outcomes according to GVHD prophylaxis.

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Data sharing would only be considered for research purposes after specific requests and internal revision and consideration.

References

  1. Stern M, de Wreede LC, Brand R, van Biezen A, Dreger P, Mohty M, et al. Sensitivity of hematological malignancies to graft-versus-host effects: an EBMT megafile analysis. Leukemia. 2014;28:2235–40.

    Article  CAS  PubMed  Google Scholar 

  2. Passweg JR, Baldomero H, Ciceri F, Corbacioglu S, de la Cámara R, Dolstra H, et al. Hematopoietic cell transplantation and cellular therapies in Europe 2021. The second year of the SARS-CoV-2 pandemic. A Report from the EBMT Activity Survey. Bone Marrow Transplant. 2023;58:647–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Forcade E, Chevret S, Finke J, Ehninger G, Ayuk F, Beelen D, et al. Impact of in vivo T-cell depletion in patients with myelodysplastic syndromes undergoing allogeneic hematopoietic stem cell transplant: a registry study from the chronic malignancies working party of the EBMT. Bone Marrow Transplant. 2022;57:768–74.

    Article  CAS  PubMed  Google Scholar 

  4. Alanazi W, Chen S, Lipton JH, Kim DD, Viswabandya A, Kumar R, et al. Post-transplant cyclophosphamide combined with anti-thymocyte globulin as graft-versus-host disease prophylaxis for allogeneic hematopoietic cell transplantation in high-risk acute myeloid leukemia and myelodysplastic syndrome. Acta Haematol. 2021;144:66–73.

    Article  CAS  PubMed  Google Scholar 

  5. Kanakry CG, O’Donnell PV, Furlong T, de Lima MJ, Wei W, Medeot M, et al. 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;32:3497–505.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Bailén R, Pascual-Cascón MJ, Guerreiro M, López-Corral L, Chinea A, Bermúdez A, et al. Post-transplantation cyclophosphamide after HLA identical compared to haploidentical donor transplant in acute myeloid leukemia: a study on behalf of GETH-TC. Transplant Cell Ther. 2022;28:204.e1–10.

    Article  PubMed  Google Scholar 

  8. Bolaños-Meade J, Reshef R, Fraser R, Fei M, Abhyankar S, Al-Kadhimi Z, et al. Three prophylaxis regimens (tacrolimus, mycophenolate mofetil, and cyclophosphamide; tacrolimus, methotrexate, and bortezomib; or tacrolimus, methotrexate, and maraviroc) versus tacrolimus and methotrexate for prevention of graft-versus-host disease with haemopoietic cell transplantation with reduced-intensity conditioning: a randomised phase 2 trial with a non-randomised contemporaneous control group (BMT CTN 1203). Lancet Haematol. 2019;6:e132–43.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Battipaglia G, Labopin M, Hamladji R, Blaise D, Chevallier P, Brissot E, et al. Post‐transplantation cyclophosphamide versus antithymocyte globulin in patients with acute myeloid leukemia undergoing allogeneic stem cell transplantation from HLA‐identical sibling donors: a retrospective analysis from the acute leukemia working party of the European society for blood and marrow transplantation. Cancer. 2021;127:209–18.

    Article  CAS  PubMed  Google Scholar 

  10. Lazzari L, Balaguer-Roselló A, Montoro J, Greco R, Hernani R, Lupo-Stanghellini MT, et al. Post-transplant cyclophosphamide and sirolimus based graft-versus-host disease prophylaxis after allogeneic stem cell transplantation for acute myeloid leukemia. Bone Marrow Transplant. 2022;57:1389–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Marco-Ayala J, Sanz J, Gómez-Seguí I, Balaguer-Rosello A, Montoro J, Guerreiro M, et al. Impact of post-transplantation cyclophosphamide on transfusion requirements in HLA-matched sibling peripheral blood stem cell transplantation. Transplant Cell Ther. 2023;29:313.e1–10.

    Article  CAS  PubMed  Google Scholar 

  12. Lin C, Vader JM, Slade M, DiPersio JF, Westervelt P, Romee R. Cardiomyopathy in patients after posttransplant cyclophosphamide–based hematopoietic cell transplantation. Cancer. 2017;123:1800–9.

    Article  CAS  PubMed  Google Scholar 

  13. Yeh J, Whited L, Saliba RM, Rondon G, Banchs J, Shpall E, et al. Cardiac toxicity after matched allogeneic hematopoietic cell transplant in the posttransplant cyclophosphamide era. Blood Adv. 2021;5:5599–607.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Duléry R, Mohty R, Labopin M, Sestili S, Malard F, Brissot E, et al. Early cardiac toxicity associated with post-transplant cyclophosphamide in allogeneic stem cell transplantation. JACC CardioOncol. 2021;3:250–9.

    Article  PubMed  PubMed Central  Google Scholar 

  15. 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 Transplant. 2009;15:1628–33.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106:2912–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Carreras E, Dufour C, Kröger N, Mohty M, editors. The EBMT handbook: hematopoietic stem cell transplantation and cellular therapies. 7th ed. Cham: Springer International Publishing; 2019. https://doi.org/10.1007/978-3-030-02278-5.

  18. Harris AC, Young R, Devine S, Hogan WJ, Ayuk F, Bunworasate U, et al. International, multicenter standardization of acute graft-versus-host disease clinical data collection: a report from the Mount Sinai acute GVHD international consortium. Biol Blood Marrow Transplant. 2016;22:4–10.

    Article  PubMed  Google Scholar 

  19. Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 diagnosis and staging working group report. Biol Blood Marrow Transplant. 2015;21:389–401.e1.

    Article  PubMed  Google Scholar 

  20. Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from Hl-A-matched sibling donors. Transplantation. 1974;18:295–304.

    Article  CAS  PubMed  Google Scholar 

  21. Moiseev IS, Pirogova OV, Alyanski AL, Babenko EV, Gindina TL, Darskaya EI, et al. Risk-adapted GVHD prophylaxis with post-transplantation cyclophosphamide in adults after related, unrelated, and haploidentical transplantations. Eur J Haematol. 2018;100:395–402.

    Article  CAS  PubMed  Google Scholar 

  22. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Mehta RS, Saliba RM, Rondon G, Al-Atrash G, Bashir Q, Hosing CM, et al. Post-transplantation cyclophosphamide versus tacrolimus and methotrexate graft-versus-host disease prophylaxis for HLA-matched donor transplantation. Transpl Cell Ther. 2022;28:695.e1–10.

    Article  CAS  Google Scholar 

  24. Bolaños-Meade J, Hamadani M, Wu J, Al Malki MM, Martens MJ, Runaas L, et al. Post-transplantation cyclophosphamide-based graft-versus-host disease prophylaxis. N Engl J Med. 2023;388:2338–48.

    Article  PubMed  PubMed Central  Google Scholar 

  25. McAdams MJ, Hyder M, Dimitrova D, Sadler JL, McKeown C, Steinberg SM, et al. Phase I/II study of reduced dosing of post-transplantation cyclophosphamide (PTCy) after HLA-haploidentical bone marrow transplantation. Blood. 2021;138:101.

    Article  Google Scholar 

  26. Lindsley RC, Saber W, Mar BG, Redd R, Wang T, Haagenson MD, et al. Prognostic mutations in myelodysplastic syndrome after stem-cell transplantation. N Engl J Med. 2017;376:536–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Della Porta MG, Alessandrino EP, Bacigalupo A, van Lint MT, Malcovati L, Pascutto C, et al. Predictive factors for the outcome of allogeneic transplantation in patients with MDS stratified according to the revised IPSS-R. Blood. 2014;123:2333–42.

    Article  PubMed  Google Scholar 

  28. Khimani F, Ranspach P, Elmariah H, Kim J, Whiting J, Nishihori T, et al. Increased infections and delayed CD4+ T cell but faster B cell immune reconstitution after post-transplantation cyclophosphamide compared to conventional GVHD prophylaxis in allogeneic transplantation. Transplant Cell Ther. 2021;27:940–8.

    Article  CAS  PubMed  Google Scholar 

  29. Pérez-Valencia AI, Cascos E, Carbonell-Ordeig S, Charry P, Gómez-Hernando M, Rodríguez-Lobato LG, et al. Incidence, risk factors, and impact of early cardiac toxicity after allogeneic hematopoietic cell transplant. Blood Adv. 2023;7:2018–31.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Hospital Clínic de Barcelona, Barcelona, Spain

    María Queralt Salas

  2. EBMT Statistical Unit, Leiden, The Netherlands

    Diderik-Jan Eikema

  3. EBMT Leiden Study Unit, Leiden, The Netherlands

    Linda Koster

  4. University Hospital Gasthuisberg, Leuven, Belgium

    Johan Maertens

  5. University Hospital | Basel, Basel, Switzerland

    Jakob Passweg

  6. University of Freiburg, Freiburg, Germany

    Jürgen Finke

  7. Erasmus MC Cancer Institute, Rotterdam, The Netherlands

    Annoek E. C. Broers

  8. Medicana International Hospital Istanbul, Istanbul, Turkey

    Yener Koc

  9. University Medical Center Hamburg, Hamburg, Germany

    Nicolaus Kröger

  10. Gazi University Faculty of Medicine, Ankara, Turkey

    Zubeyde Nur Ozkurt

  11. Hospital Regional de Málaga, Malaga, Spain

    María Jesús Pascual-Cascon

  12. Medical Clinic and Policinic 1, Leipzig, Germany

    Uwe Platzbecker

  13. University Hospital Maastricht, Maastricht, The Netherlands

    Gwendolyn Van Gorkom

  14. University Hospital | Essen, Duesseldorf, Germany

    Thomas Schroeder

  15. Fundación Jiménez Díaz, Madrid, Spain

    José Luis López-Lorenzo

  16. Grande Ospedale Metropolitano Bianchi Melacrino Morelli – Centro Unico Trapianti A. Neri, Reggio C, Italy

    Massimo Martino

  17. Universita Cattolica S. Cuore, Rome, Italy

    Patrizia Chiusolo

  18. Robert Bosch Krankenhaus, Stuttgart, Germany

    Martin Kaufmann

  19. Fondazione IRCCS – Ca’ Granda – Ospedale Maggiore Policlinico IRCCS, Milan, Italy

    Francesco Onida

  20. Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy

    Carmelo Gurnari

  21. Translational Hematology and Oncology Research Department, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, USA

    Carmelo Gurnari

  22. University of Cologne, Cologne, Germany

    Christof Scheid

  23. Central Clinical Hospital, The Medical University of Warsaw, Warsaw, Poland

    Joanna Drozd-Sokolowska

  24. University College London Hospitals NHS Trust, London, UK

    Kavita Raj & Donal P. McLornan

  25. Hopital Saint-Louis, APHP, Université de Paris Cité, Paris, France

    Marie Robin

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Contributions

DM, MR, RK, DJE, and MQS designed the study. DJE did the statistical analysis. DM, DJE, and MQS interpreted the results and wrote the manuscript. MR and RF provided valuable support for interpreting the results and statement of the conclusions. LK, JM, JP, FF, AECB, JK, NK, ZNO, MJPC, UP, GVG, TM, TLLP, MM, SS, MK, FO, CG, CS, and JDS LGRL provided valuable input into the study and reviewed and approved the manuscript.

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Correspondence to Donal P. McLornan.

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Salas, M.Q., Eikema, DJ., Koster, L. et al. Impact of post-transplant cyclophosphamide (PTCy)-based prophylaxis in matched sibling donor allogeneic haematopoietic cell transplantation for patients with myelodysplastic syndrome: a retrospective study on behalf of the Chronic Malignancies Working Party of the EBMT. Bone Marrow Transplant 59, 479–488 (2024). https://doi.org/10.1038/s41409-023-02159-1

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