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Cytogenetic and molecular risk-driven conditioning intensity in acute myeloid leukemia patients undergoing stem cell transplantation with post-transplant cyclophosphamide: a study from the acute leukemia working party of the EBMT

Bone Marrow Transplantation volume 60, pages 529–534 (2025)Cite this article

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Abstract

We retrospectively analyzed the impact of conditioning intensity on transplant outcomes according to their cytogenetic/molecular risk in a cohort of 1823 patients with acute myeloid leukemia (AML) and intermediate- or adverse-risk cytogenetics in first complete remission (CR1). These patients received their first hematopoietic stem cell transplantation (HSCT) using post-transplant cyclophosphamide (PTCy). The intermediate-risk cytogenetic group included 1386 (76%) patients, and 608 (34%) had mutated FLT3-ITD. Myeloablative conditioning was used in 930 patients (51%), while 1130 (62%) received an intensified conditioning (score ≥2.5) based on the transplant conditioning intensity (TCI) score. Conditioning intensity using the myeloablative/reduced intensity stratification did not impact transplant outcomes across the entire cohort. However, a higher TCI score was associated with a lower risk of relapse, with no effect on survival. In specific cytogenetic risk groups, a higher TCI score did not influence outcomes in the adverse-risk group. In the intermediate-risk group, the impact varied with FLT3-ITD status. Patients with FLT3-ITD mutation who received a higher TCI showed a beneficial effect on relapse, leukemia-free survival (LFS), and overall survival. Conversely, in FLT3-ITD wild-type patients, more intense conditioning had a detrimental effect on graft-versus-host disease-free, and relapse-free survival with no effect on other outcomes. In conclusion, for AML patients in CR1 undergoing HSCT with PTCy, it is crucial to consider cytogenetic risk and molecular status when selecting the conditioning regimen. Intensive conditioning should be considered for patients with intermediate-risk cytogenetics and mutated FLT3-ITD but should probably be avoided for those with wild-type FLT3-ITD.

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Data availability

The dataset supporting the conclusions of this article are available in the ALWP of the EBMT in Saint Antoine Hospital, Paris.

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Author information

Authors and Affiliations

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

    Jaime Sanz & Juan Montoro

  2. EBMT Paris Office, Hospital Saint Antoine, Paris, France

    Myriam Labopin

  3. Erasmus MC Cancer Institute, Rotterdam, The Netherlands

    Jurjen Versluis

  4. Programme de Transplantation & Therapie Cellulaire—Marseille, Marseille, France

    Didier Blaise

  5. Hematology and Bone Marrow transplant Unit, San Raffaele Scientific Institute IRCCS, Milano, Italy

    Lorenzo Lazzari, Simona Piemontese & Fabio Ciceri

  6. University Hospital Maastricht, Maastricht, The Netherlands

    Gwendolyn Van Gorkom

  7. Leiden University Medical Center, Leiden, The Netherlands

    Peter von dem Borne

  8. Centre Hospitalier Lyon Sud, Lyon, France

    Loron Sandrine

  9. BMT Unit, Department of Haematology, Institute of Haematology and Oncology, IDIBAPS, Hospital Clinic, University of Barcelona, Josep Carreras Leukaemia Research Foundation, Barcelona, Spain

    Montserrat Rovira

  10. Dél-pesti Centrumkórház, Budapest, Hungary

    Péter Reményi

  11. CHU Nantes, Nantes, France

    Patrice Chevallier

  12. Hospital Gregorio Marañón, Madrid, Spain

    Mi Kwon

  13. Hannover Medical School, Hannover, Germany

    Matthias Eder

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

    Jan Vydra

  15. Hôpital Saint-Antoine, Sorbonne University, INSERM UMRs 938, Paris, France

    Eolia Brissot & Mohamad Mohty

  16. Hematology, BMT and Institute of Cellular Therapy, University of Patras, Patras, Greece

    Alexandros Spyridonidis

  17. Vita-Salute San Raffaele University, Milano, Italy

    Fabio Ciceri

Authors
  1. Jaime Sanz
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  2. Myriam Labopin
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  3. Jurjen Versluis
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  4. Didier Blaise
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  5. Lorenzo Lazzari
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  6. Juan Montoro
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  7. Gwendolyn Van Gorkom
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  9. Loron Sandrine
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  14. Matthias Eder
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  20. Fabio Ciceri
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Contributions

JS, ML, AS, MM, SP, and FC: designed the study. ML: performed statistical analysis and helped with the interpretation of the results. JS: wrote the manuscript. JV, DB, JP, JP, JM, GVG, PVDB, HLW, MR, PR, PC, MK, ME, JV, and EB: provided cases for the study. All authors reviewed and approved the manuscript.

Corresponding author

Correspondence to Jaime Sanz.

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The authors declare no competing interests.

Ethics approval and consent to participate

The scientific board of the ALWP of EBMT approved this study. All patients gave written informed consent for the use of their data. All methods were performed in accordance with the relevant guidelines and regulations.

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Not applicable for individual patient data. This is a pooled analysis.

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Sanz, J., Labopin, M., Versluis, J. et al. Cytogenetic and molecular risk-driven conditioning intensity in acute myeloid leukemia patients undergoing stem cell transplantation with post-transplant cyclophosphamide: a study from the acute leukemia working party of the EBMT. Bone Marrow Transplant 60, 529–534 (2025). https://doi.org/10.1038/s41409-025-02527-z

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