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Interplay between acute graft-versus-host disease and graft-versus-leukemia effect in pediatric acute myeloid leukemia patients undergoing allogeneic hematopoietic stem cell transplantation: implications for relapse incidence and survival – an EBMT PDWP retrospective study

Bone Marrow Transplantation (2025)Cite this article

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Abstract

The interplay between graft-versus-host disease (aGVHD) and the graft-versus-leukemia (GVL) effect in children with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (HSCT) remains complex. This EBMT Pediatric Diseases Working Party (PDWP) retrospective analysis of 2374 pediatric AML patients evaluated the impact of aGVHD on relapse incidence (RI), non-relapse mortality (NRM), overall survival (OS), and leukemia-free survival (LFS). Grade III/IV aGVHD significantly reduced RI (HR: 0.61, p = 0.01) while significantly increasing NRM (HR: 4.51, p < 0.001), offsetting any benefits in OS and LFS. Grade II aGVHD increased NRM (HR: 2.07, p = 0.002) without affecting RI or OS, while grade I aGVHD had no significant impact on these outcomes. Patients with Grade II or higher aGVHD were at greater risk of both chronic (c)GvHD (HR: 1.98 for Grade II; HR: 4.33 for Grade III/IV, p < 0.001) and extensive cGVHD (HR: 2.52 for Grade II; HR: 4.91 for Grade III/IV, p < 0.001). These findings highlight the challenge of mitigating NRM while preserving the GVL effect to optimize disease control and long-term survival in pediatric AML. This study provides critical insights for refining post-transplant strategies in this population.

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Fig. 1: Landmark analysis at day 100.

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Data availability

In order to have access to the data, a request has to be made to the chair of the PDWP of EBMT and the study coordinator. The scientific boards of the PDWP of the EBMT approved this study. All the analyses were performed according to the EBMT guidelines. EBMT minimum essential data forms are submitted to the registry by transplant Center personnel following written informed consent from patients in accordance with the Centers’ ethical research guidelines.

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Acknowledgements

The authors want to acknowledge all contributing Centers. The authors declare that they have no relevant conflict of interest and no competing financial interests.

Author information

Author notes

  1. These authors contributed equally: A. Bertaina, M. Maffeis.

Authors and Affiliations

  1. Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford School of Medicine, Stanford, CA, USA

    A. Bertaina

  2. Pediatric Oncohematology and Bone Marrow Unit, Children’s Hospital, ASST Spedali Civili, Brescia, Italy

    M. Maffeis

  3. Pediatric Stem Cell Transplantation Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy

    G. Lucchini & A. Balduzzi

  4. EBMT Statistical Unit, Hôpital Saint-Antoine, Paris, France

    J. E. Galimard

  5. EBMT Paris Study Unit, Hôpital Saint-Antoine, Paris, France

    A. Dalissier

  6. Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University of Regensburg, Regensburg, Germany

    K. Kleinschmidt & S. Corbacioglu

  7. Cansearch Research platform for pediatric oncology and hematology, Faculty of Medicine, Department of Pediatrics, Gynecology and Obstetrics, University of Geneva and Division of Pediatric Oncology and Hematology, Department of Women, Child and Adolescent, University Geneva Hospitals, Geneva, Switzerland

    M. Ansari

  8. Pierre and Marie Curie Center, University of Health Sciences, Algiers, Algeria

    M. Benakli

  9. Paediatric Bone Marrow Transplant Unit, Bristol Royal Hospital for Children, Bristol, UK

    O. C. Mirci-Danicar

  10. Department of Paediatric Bone Marrow Transplant, Royal Manchester Children’s Hospital, Manchester, UK

    O. C. Mirci-Danicar

  11. Department of Hematology/Oncology, Cell and Gene Therapy, IRCSS Bambino Gesù Children’s Hospitale, Rome, Italy

    D. Pagliara

  12. Hôpital Robert Debré, Pediatric Hematology and Immunology Department, GHU AP-HP Nord Université Paris Cité, Paris, France

    J. H. Dalle

  13. King Faisal Specialist Hospital & Research Centre (Paeds), Riyadh, Saudi Arabia

    A. Al Ahmari

  14. The Russian Federation Children’s Research Hospital, Moscow, Russian Federation

    E. Skorobogatova

  15. Institut d’Hematologie et Oncologie Pediatrique, Hospices Civils de Lyon, Lyon, France

    C. Renard

  16. University Hospital, Collegium Medicum UMK Pediatric Hematology and Oncology, Bydgoszcz, Poland

    J. Styczynski

  17. King Hussein Cancer Centre, Pediatric BMT Program, Amman, Jordan

    R. Rihani

  18. Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic

    R. Formankova

  19. School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy

    A. Balduzzi

  20. CHU Bordeaux Groupe Hospitalier Pellegrin-Enfants, Bordeaux, France

    C. Jubert

  21. St Sophia Children’s hospital Oncology center, Athens, Greece

    E. Goussetis

  22. Dept for Children and Adolescent medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

    M. Ifversen

  23. Willem-Alexander Children’s Hospital, Leiden University Medical Center, Leiden, The Netherlands

    A. Lankester

  24. Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands

    B. Versluijs

  25. Oncology Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia

    M. Aljurf

  26. Division for Stem Cell Transplantation and Immunology, Department of Pediatrics, Goethe University, Frankfurt am Main, Germany

    P. Bader

  27. Department of Pediatric Hematology, Oncology, and BMT, Wroclaw Medical University, Wroclaw, Poland

    K. Kalwak

Authors
  1. A. Bertaina
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  2. M. Maffeis
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  3. G. Lucchini
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  4. J. E. Galimard
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Contributions

AB, MM, SC, KK, JEG, AD and GL designed the study and wrote the first version of the manuscript. MM completed the data interpretation and contributed to writing the final version of the manuscript. JEG performed all statistical analyses. KK (Kleinschmidt), MA, MB, OMD, DP, JHD, AAA, ES, CR, JS, RR, RF, AB, CJ, EG, MI, AL, BV, MA and PB provided clinical data and reviewed the manuscript. All authors approved the final version of the manuscript.

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Correspondence to M. Maffeis.

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Bertaina, A., Maffeis, M., Lucchini, G. et al. Interplay between acute graft-versus-host disease and graft-versus-leukemia effect in pediatric acute myeloid leukemia patients undergoing allogeneic hematopoietic stem cell transplantation: implications for relapse incidence and survival – an EBMT PDWP retrospective study. Bone Marrow Transplant (2025). https://doi.org/10.1038/s41409-025-02748-2

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