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Frequency and impact of somatic co-occurring mutations on post-transplant outcomes in acute myeloid leukemia: a multicenter registry analysis on behalf of the EBMT ALWP

Bone Marrow Transplantation (2025)Cite this article

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Abstract

Acute myeloid leukemia (AML) includes genetically defined subsets. In allogeneic hematopoietic cell transplantation (allo-HCT), the frequency and prognosis of gene-gene interactions may differ from those of patients treated with chemotherapy alone. In this study, adult patients (N = 952) with AML allografted between 2015 and 2023, with available next generation sequencing (NGS) at diagnosis were included. Most frequent mutations were DNMT3A (24%), FLT3-ITD (21%), NPM1 (21%), RUNX1 (16%), NRAS (16%), TET2 (14%), and IDH2 (12%). Multiple correspondence analysis identified distinct groups of co-occurring mutations. Outcome analysis was performed on 646 AML patients allografted in first complete remission (CR1). Six non-overlapping groups were constructed: 1) TP53 mutation (N = 47); 2) NPM1 mutation (N = 129); 3) FLT3-ITD and/or DNMT3A mutation (N = 128); 4) SRSF2 and/or ASXL1 and/or RUNX1 mutation (SAR group) (N = 132); 5) IDH1 and/or IDH2 and/or TET2 mutation (N = 43); and 6) all ten genes unmutated (N = 167). In multivariable analysis, TP53 mutation, adverse karyotype, and age negatively affected leukemia-free survival (LFS) and overall survival (OS). OS was additionally negatively affected when the ten genes were unmutated. Notably, outcomes were excellent for SAR mutations (2-year LFS 76%, OS 84%), indicating allo-HCT in CR1 can overcome their adverse risk at diagnosis.

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Fig. 1: Somatic mutations in allografted AML patients.
Fig. 2: Association of somatic mutations in allografted AML patients.
Fig. 3: Impact of somatic mutation groups on post-transplant outcomes for patients allografted in CR1.

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Data availability

The data analyzed in this study were provided and approved by the ALWP of the EBMT. All relevant data supporting the findings of this study are available within the Article and the Supplementary Material. Requests for access to EBMT study data from qualified external researchers will be reviewed by the relevant working party in accordance with EBMT’s data-sharing policies. This process ensures the protection of patient privacy, maintains data security and integrity, and promotes scientific and medical innovation. Additional details on data-sharing criteria and the request process can be obtained by contacting ebmt.do-paris@ebmt.org. Individual patient-level data will not be shared.

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Acknowledgements

Patients and caregivers, EBMT participating centers, the ALWP statistical and data management team, particularly Aleksandra (Sasha) Gavrilina, as well as the leadership team. This was presented in part during the American Society of Hematology meeting in San Diego, December 2023.

Author information

Authors and Affiliations

  1. Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon

    Ali Bazarbachi & Iman Abou Dalle

  2. EBMT Paris Study Unit, Sorbonne University, Saint-Antoine Hospital, AP-HP, INSERM UMRs 938, Paris, France

    Jacques-Emmanuel Galimard & Myriam Labopin

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

    Jaime Sanz

  4. First Affiliated Hospital of Zhejiang University School of Medicine, Kunming, China

    He Huang

  5. University Hospital Brno, Brno, Czech Republic

    Jiri Mayer

  6. Hospital Clínico Universitario-INCLIVA. University of Valencia, Valencia, Spain

    Carlos Solano

  7. Hôpitaux Universitaires Strasbourg, Hematology Oncology Department, Strasbourg, France

    Bruno Lioure

  8. Vilnius University Hospital Santaros Klinikos and Vilnius University, Vilnius, France

    Laimonas Griskevicius

  9. University Hospital Gasthuisberg, Leuven, Belgium

    Johan Maertens

  10. Turku University Hospital, Turku, Finland

    Maija Itälä-Remes

  11. Tartu University Hospital, Tartu, Estonia

    Ain Kaare

  12. Hematology oncology and cellular therapy department, University Hospital of Poitiers, Poitiers, France

    Maria-Pilar Gallego-Hernanz

  13. Goethe-University Frankfurt, Frankfurt Main, Germany

    Gesine Bug

  14. ICO-Hospital Universitari Germans Trias i Pujol, Josep Carreras Research Institute, Badalona, Spain

    Josep-Maria Ribera

  15. Antwerp University Hospital (UZA), Antwerp E, Belgium

    Alain Gadisseur

  16. Augsburg University Hospital and Medical Faculty, Augsburg, Germany

    Christoph Schmid

  17. Department of Hematology, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain

    Mi Kwon

  18. Cliniques Universitaires St. Luc, Brussels, Belgium

    Xavier Poiré

  19. Azienda Ospedali Riuniti di Ancona, Ancona, Italy

    Paola Coccia

  20. Hospital Univ. Virgen de las Nieves, Granada, Spain

    Manuel Jurado Chacón

  21. University of Liege, Liege, Belgium

    Frédéric Baron

  22. Blood and Marrow Transplant Unit, Queen Elizabeth Hospital, Birmingham, UK

    Charles Craddock

  23. Service d’hématologie et des maladies du sang, Hôpital Saint-Antoine, Paris, France

    Eolia Brissot

  24. Hematology Division, Chaim Sheba Medical Center, Tel-Hashomer, Israel

    Arnon Nagler

  25. University Vita-Salute, IRCCS Ospedale San Raffaele, Haematology and BMT, Milano, Italy

    Fabio Ciceri

  26. Sorbonne University, Saint-Antoine Hospital, AP-HP, INSERM UMRs 938, Paris, France

    Mohamad Mohty

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  1. Ali Bazarbachi
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  2. Jacques-Emmanuel Galimard
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Contributions

ABa proposed the study, interpreted the data, and wrote the manuscript. J-EG and MMo participated in study design, data interpretation, and manuscript editing. J-EG performed the statistical analysis. IAD and MLa contributed to data interpretation and manuscript revision. JS, HH, JM, CS, BL, LG, JMa, MI-R, AK, M-PG-H, GB, J-MR, AG, CSc, MK, XP, PC, MJC, FB, CC, EB, AN, and FC collected and updated patient data, and critically reviewed and approved the manuscript. All authors reviewed the final version, approved the data presented, and agreed with the conclusions of the work.

Corresponding author

Correspondence to Ali Bazarbachi.

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Competing interests

The authors declare no competing interests.

Ethical approval and consent to participate

This is a retrospective, registry-based, multicenter study utilizing patient data collected and approved by the Acute Leukemia Working Party (ALWP) of the EBMT. The EBMT is a collaborative network comprising more than 600 transplant centers that are required to report all consecutive HCTs and subsequent follow-ups on an annual basis. Routine audits are performed to ensure data accuracy and completeness. Since January 2003, all participating transplant centers have been required to obtain written informed consent from patients prior to data registration with the EBMT, in accordance with the ethical principles outlined in the Declaration of Helsinki (1975).

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Bazarbachi, A., Galimard, JE., Abou Dalle, I. et al. Frequency and impact of somatic co-occurring mutations on post-transplant outcomes in acute myeloid leukemia: a multicenter registry analysis on behalf of the EBMT ALWP. Bone Marrow Transplant (2025). https://doi.org/10.1038/s41409-025-02770-4

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