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Addition of mycophenolate mofetil to a calcineurin inhibitor and post-transplant cyclophosphamide results in lower incidence of extensive chronic graft-versus-host disease in HLA-matched allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia in complete remission: a matched-pair analysis on behalf of the Acute Leukemia Working Party of the EBMT

Bone Marrow Transplantation volume 60, pages 1146–1151 (2025)Cite this article

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Abstract

Whether one or two agents added to post-transplant cyclophosphamide (PTCy) are needed in HLA-matched allogeneic hematopoietic stem cell transplantation (allo-HSCT) with peripheral blood stem cells (PBSC) is debated. We retrospectively compared PTCy in association with a calcineurin inhibitor (PTCy+CNI) or with a CNI plus mycophenolate mofetil (PTCy+CNI+MMF) in adult patients transplanted for acute myeloid leukemia in first complete remission and receiving PBSC in the period from 2010 to 2020. Propensity score matching was performed using exact matching for donor type (related or unrelated) and the nearest neighbor for other variables (i.e. age, adverse cytogenetics, Karnofsky performance status, patient and donor cytomegalovirus serology, conditioning intensity). Each group comprised 146 patients, with 63% in total undergoing matched unrelated-allo-HSCT. Median follow up was longer for PTCy+CNI (36 [IQR 31–39] months versus 25 [IQR 19–30] months for PTCy+CNI+MMF, p < 0.01). At 2 years, PTCy+CNI was associated with a higher incidence of extensive chronic GVHD (16% [95% CI 10–22] versus 6% [95% CI 3–12] for PTCy+CNI+MMF, p < 0.03) while no differences were observed for all the other transplant outcomes. Addition of MMF to PTCy and CNI may help to prevent extensive chronic GVHD in HLA-matched allo-HSCT with PBSC.

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Fig. 1: Transplant outcomes according to graft-versus-host disease prophylaxis.
Fig. 2: Transplant outcomes according to graft-versus-host disease prophylaxis.

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Data availability

The final analysis dataset will be available upon specific request to the Working Party Chair.

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Acknowledgements

The authors thank Emmanuelle Polge from the office of the ALWP of the EBMT, and the clinical staff and investigators involved in this research, and they especially thank the patients who took part.

Author information

Authors and Affiliations

  1. Federico II University of Naples, Hematology Department, Naples, Italy

    Giorgia Battipaglia

  2. Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy

    Giorgia Battipaglia & Arnon Nagler

  3. EBMT Paris study office, Paris, France

    Myriam Labopin & Mohamad Mohty

  4. Hematology Department, Hôpital Saint Antoine, Service d’Hématologie et Thérapie Cellulaire, Paris, France

    Myriam Labopin & Mohamad Mohty

  5. Sorbonne Universités, UPMC Univ Paris 06, INSERM, Centre de Recherche Saint-Antoine (CRSA), Paris, France

    Myriam Labopin & Mohamad Mohty

  6. First State Pavlov Medical University of St. Petersburg, Raisa Gorbacheva Memorial Research Institute for Paediatric Oncology, Haematology and Transplantation - St-Petersburg, St-Petersburg, Russia

    Aleksandr Kulagin

  7. Erasmus MC Cancer Institute, University Medical Center Rotterdam, Department of Haematology - Rotterdam, Rotterdam, The Netherlands

    Jurgen Versluis

  8. Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Goda Choi

  9. VU University Medical Center, Department of Haematology – Amsterdam, Amsterdam, The Netherlands

    Ellen Meijer

  10. Hospital Clinic, BMT Unit, Dept. of Haematology, Institute of Haematology & Oncology, IDIBAPS, Institut Josep Carreras– Barcelona, Barcelona, Spain

    Montserrat Rovira

  11. Department of Internal Medicine, Division of Hematology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands

    Gwendolyn van Gorkom

  12. Department of Hematology, Hospital General Universitario Gregorio Marañon, Instituto de Investigacion Sanitaria Gregorio Marañon, Departamento de Medicina, Universidad Computense de Madrid, Madrid, Spain

    Mi Kwon

  13. Medicana International Hospital Istanbul, Bone Marrow Transplant Unit – Istanbul, Istanbul, Turkey

    Yener Koc

  14. Institute of Haematology and Blood Transfusion, Prague, Czech Republic

    Jan Vydra

  15. Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico A. Gemelli IRCCS, Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, Roma, Italy

    Patrizia Chiusolo

  16. Clatterbridge Cancer Centre - Liverpool, Royal Liverpool University Hospital, Clatterbridge Cancer Centre NHS Foundation Trust, Division of Stem Cell Transplantation and Haematology – Liverpool, Liverpool, UK

    Amit Patel

  17. Ospedale San Raffaele s.r.l., Haematology and BMT, Milano, Italy

    Simona Piemontese, Annalisa Ruggeri & Fabio Ciceri

  18. Hematology Department, Hospital Universitari i Politècnic La Fe, Departament de Medicina Universitat de Valencia, CIBERONC, Instituto Carlos III, Valencia, Spain

    Jaime Sanz

  19. Chaim Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel

    Arnon Nagler

Authors
  1. Giorgia Battipaglia
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Contributions

GB designed the study and wrote the manuscript, ML performed the statistical analysis, SP, JS, AR, MM, AN and FC revised the manuscript, and all the authors reviewed the final version. AK, JV, GC, EM, MR, GVG, MK, YK, JV, PC, AP, were the principal investigators at the centers recruiting the highest number of patients to the study.

Corresponding author

Correspondence to Giorgia Battipaglia.

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Battipaglia, G., Labopin, M., Kulagin, A. et al. Addition of mycophenolate mofetil to a calcineurin inhibitor and post-transplant cyclophosphamide results in lower incidence of extensive chronic graft-versus-host disease in HLA-matched allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia in complete remission: a matched-pair analysis on behalf of the Acute Leukemia Working Party of the EBMT. Bone Marrow Transplant 60, 1146–1151 (2025). https://doi.org/10.1038/s41409-025-02610-5

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