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Post-transplant cyclophosphamide, calcineurin inhibitor, and mycophenolate mofetil compared to anti-thymocyte globulin, calcineurin inhibitor, and methotrexate combinations as graft-versus-host disease prophylaxis post allogeneic stem cell transplantation from sibling and unrelated donors in patients with acute myeloid leukemia: a study on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

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Abstract

Post-transplant cyclophosphamide plus calcineurin inhibitor (CNI)(tacrolimus or cyclosporine A) plus mycophenolate mofetil (PTCy/TAC or CSA/MMF) and anti-thymocyte globulin plus CNI (tacrolimus or cyclosporine A) plus methotrexate (ATG/TAC or CSA/MTX) are common graft-versus-host disease (GVHD) prophylaxis regimens. We compared the two regimens in patients with acute myeloid leukemia (AML) undergoing allogeneic transplantation from matched siblings or unrelated donors. 402 received PTCy/TAC or CSA/MMF and 5648 received ATG/TAC or CSA/MTX. Patients in the PTCy-based group were younger (48.7 vs. 51.5 years, p = 0.024) and there was a higher frequency of patient cytomegalovirus seropositivity and female donor to male patient combination in this group (77.8% vs. 71.8%, p = 0.009 and 18.4% vs. 14.4%, p = 0.029, respectively). More patients in the PTCy-based group received reduced-intensity conditioning (51.5% vs. 41%, p < 0.0001). No differences were observed in the incidence of acute GVHD grade II–IV and III–IV (21.2% vs. 20.4%, p = 0.92 and 8.1% vs. 6%, p = 0.1) or 2-year total and extensive chronic GVHD (33.7% vs. 30%, p = 0.09 and 10.7% vs. 11.2%, p = 0.81) between the groups. In the multivariate analysis, all transplant outcomes did not differ between the groups. PTCy/CNI/MMF and ATG/CNI/MTX are alternative regimens for GVHD prophylaxis in AML patients.

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AN, ML, FC, and MM had full access to all study data (available upon data-specific request).

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Acknowledgements

We thank all the EBMT centers and national registries for contributing patients to this study (Supplementary appendix material). We also thank the data managers for their excellent work.

Author information

Authors and Affiliations

  1. Division of Hematology, Chaim Sheba Medical Center, Tel Hashomer, Israel

    Arnon Nagler

  2. EBMT Paris Study Office; Department of Haematology, Saint Antoine Hospital; INSERM UMR 938, Sorbonne University, Paris, France

    Myriam Labopin & Mohamad Mohty

  3. Department of Haematology, Saint Antoine Hospital, Sorbonne University; INSERM UMR 938, Paris, France

    Myriam Labopin, Eolia Brissot & Mohamad Mohty

  4. Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland

    Ryszard Swoboda

  5. University Hospital of Essen, Essen, Germany

    Thomas Schroeder

  6. Centre Pierre et Marie Curie, Alger, Algeria

    Rose-Marie Hamladji

  7. Hospital Santaros Klinikos, Vilnius University, Vilnius, Lithuania

    Laimonas Griskevicius

  8. HUCH Comprehensive Cancer Center, Helsinki, Finland

    Urpu Salmenniemi

  9. Department of Oncology and Hematology, University of Milan and Azienda Socio-Sanitaria Territoriale, Papa Giovanni XXIII, Bergamo, Italy

    Alessandro Rambaldi

  10. Karolinska University Hospital, Stockholm, Sweden

    Stephan Mielke

  11. RM Gorbacheva Research Institute, Pavlov University, Petersburg, Russia

    Alexander Kulagin

  12. University Hospital of Basel, Basel, Switzerland

    Jakob Passweg

  13. University of Heidelberg, Heidelberg, Germany

    Thomas Luft

  14. Oslo University Hospital, Rikshospitalet, Oslo, Norway

    Tobias Gedde-Dahl

  15. Hôpital Haut-Leveque, CHU Bordeaux, Pessac, France

    Edouard Forcade

  16. Silesian Medical Academy, Katowice, Poland

    Grzegorz Helbig

  17. University of Muenster, Muenster, Germany

    Matthias Stelljes

  18. Gustave Roussy Cancer Campus, Villejuif, France

    Cristina Castilla-Llorente

  19. Department of Internal Medicine, Bone Marrow Transplantation Unit, University Hospital of Patras, Patras, Greece

    Alexandros Spyridonidis

  20. Department of Haematology and BMT, IRCCS Osspedale San Raffaele; Vita-Salute San Raffaele University, Milano, Italy

    Fabio Ciceri

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  1. Arnon Nagler
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Contributions

AN wrote the manuscript, designed the study, and interpreted the data. ML and MM designed the study, performed the statistical analyses, interpreted the data, and edited the manuscript. RS helped with writing the first draft of the manuscript. TS, RMH, LG, US, AR, SM, AK, JP, PD, TGD, EF, GH, MS, CCL, AS, EB, and FC reviewed the manuscript and provided clinical data. All authors approved the final version of the manuscript.

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Correspondence to Arnon Nagler.

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Nagler, A., Labopin, M., Swoboda, R. et al. Post-transplant cyclophosphamide, calcineurin inhibitor, and mycophenolate mofetil compared to anti-thymocyte globulin, calcineurin inhibitor, and methotrexate combinations as graft-versus-host disease prophylaxis post allogeneic stem cell transplantation from sibling and unrelated donors in patients with acute myeloid leukemia: a study on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Bone Marrow Transplant (2024). https://doi.org/10.1038/s41409-024-02284-5

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