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

A Bertaina^#¹, M Maffeis^#², G Lucchini³, J E Galimard⁴, A Dalissier⁵, K Kleinschmidt⁶, M Ansari⁷, M Benakli⁸, O C Mirci-Danicar^{9

10}, D Pagliara¹¹, J H Dalle¹², A Al Ahmari¹³, E Skorobogatova¹⁴, C Renard¹⁵, J Styczynski¹⁶, R Rihani¹⁷, R Formankova¹⁸, A Balduzzi^{3

19}, C Jubert²⁰, E Goussetis²¹, M Ifversen²², A Lankester²³, B Versluijs²⁴, M Aljurf²⁵, P Bader²⁶, S Corbacioglu⁶, K Kalwak²⁷

Affiliations

¹ Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford School of Medicine, Stanford, CA, USA.
² Pediatric Oncohematology and Bone Marrow Unit, Children's Hospital, ASST Spedali Civili, Brescia, Italy. marianna.maffeis@asst-spedalicivili.it.
³ Pediatric Stem Cell Transplantation Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.
⁴ EBMT Statistical Unit, Hôpital Saint-Antoine, Paris, France.
⁵ EBMT Paris Study Unit, Hôpital Saint-Antoine, Paris, France.
⁶ Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University of Regensburg, Regensburg, Germany.
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.
⁸ Pierre and Marie Curie Center, University of Health Sciences, Algiers, Algeria.
⁹ Paediatric Bone Marrow Transplant Unit, Bristol Royal Hospital for Children, Bristol, UK.
¹⁰ Department of Paediatric Bone Marrow Transplant, Royal Manchester Children's Hospital, Manchester, UK.
¹¹ Department of Hematology/Oncology, Cell and Gene Therapy, IRCSS Bambino Gesù Children's Hospitale, Rome, Italy.
¹² Hôpital Robert Debré, Pediatric Hematology and Immunology Department, GHU AP-HP Nord Université Paris Cité, Paris, France.
¹³ King Faisal Specialist Hospital & Research Centre (Paeds), Riyadh, Saudi Arabia.
¹⁴ The Russian Federation Children's Research Hospital, Moscow, Russian Federation.
¹⁵ Institut d'Hematologie et Oncologie Pediatrique, Hospices Civils de Lyon, Lyon, France.
¹⁶ University Hospital, Collegium Medicum UMK Pediatric Hematology and Oncology, Bydgoszcz, Poland.
¹⁷ King Hussein Cancer Centre, Pediatric BMT Program, Amman, Jordan.
¹⁸ Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
¹⁹ School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
²⁰ CHU Bordeaux Groupe Hospitalier Pellegrin-Enfants, Bordeaux, France.
²¹ St Sophia Children's hospital Oncology center, Athens, Greece.
²² Dept for Children and Adolescent medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
²³ Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, The Netherlands.
²⁴ Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
²⁵ Oncology Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
²⁶ Division for Stem Cell Transplantation and Immunology, Department of Pediatrics, Goethe University, Frankfurt am Main, Germany.
²⁷ Department of Pediatric Hematology, Oncology, and BMT, Wroclaw Medical University, Wroclaw, Poland.

^# Contributed equally.

PMID: 41326788
DOI: 10.1038/s41409-025-02748-2

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

A Bertaina et al. Bone Marrow Transplant. 2025.

. 2025 Dec 1.

doi: 10.1038/s41409-025-02748-2. Online ahead of print.

Authors

Affiliations

¹ Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford School of Medicine, Stanford, CA, USA.
² Pediatric Oncohematology and Bone Marrow Unit, Children's Hospital, ASST Spedali Civili, Brescia, Italy. marianna.maffeis@asst-spedalicivili.it.
³ Pediatric Stem Cell Transplantation Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.
⁴ EBMT Statistical Unit, Hôpital Saint-Antoine, Paris, France.
⁵ EBMT Paris Study Unit, Hôpital Saint-Antoine, Paris, France.
⁶ Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University of Regensburg, Regensburg, Germany.
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.
⁸ Pierre and Marie Curie Center, University of Health Sciences, Algiers, Algeria.
⁹ Paediatric Bone Marrow Transplant Unit, Bristol Royal Hospital for Children, Bristol, UK.
¹⁰ Department of Paediatric Bone Marrow Transplant, Royal Manchester Children's Hospital, Manchester, UK.
¹¹ Department of Hematology/Oncology, Cell and Gene Therapy, IRCSS Bambino Gesù Children's Hospitale, Rome, Italy.
¹² Hôpital Robert Debré, Pediatric Hematology and Immunology Department, GHU AP-HP Nord Université Paris Cité, Paris, France.
¹³ King Faisal Specialist Hospital & Research Centre (Paeds), Riyadh, Saudi Arabia.
¹⁴ The Russian Federation Children's Research Hospital, Moscow, Russian Federation.
¹⁵ Institut d'Hematologie et Oncologie Pediatrique, Hospices Civils de Lyon, Lyon, France.
¹⁶ University Hospital, Collegium Medicum UMK Pediatric Hematology and Oncology, Bydgoszcz, Poland.
¹⁷ King Hussein Cancer Centre, Pediatric BMT Program, Amman, Jordan.
¹⁸ Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
¹⁹ School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
²⁰ CHU Bordeaux Groupe Hospitalier Pellegrin-Enfants, Bordeaux, France.
²¹ St Sophia Children's hospital Oncology center, Athens, Greece.
²² Dept for Children and Adolescent medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
²³ Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, The Netherlands.
²⁴ Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
²⁵ Oncology Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
²⁶ Division for Stem Cell Transplantation and Immunology, Department of Pediatrics, Goethe University, Frankfurt am Main, Germany.
²⁷ Department of Pediatric Hematology, Oncology, and BMT, Wroclaw Medical University, Wroclaw, Poland.

^# Contributed equally.

PMID: 41326788
DOI: 10.1038/s41409-025-02748-2

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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Conflict of interest statement

Competing interests: The authors declare no competing interests.

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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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

References

LinkOut - more resources

Full Text Sources