Abstract
In the past decades, treatment for acute myeloid leukemia (AML) has advanced, but allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains vital for improving survival in most patients. This retrospective study, conducted on behalf of the Acute Leukemia Working Party of the EBMT, examines the impact of fludarabine dose in reduced-intensity conditioning regimens on clinical outcomes in patients over 50 years old with AML in first complete remission, without chronic kidney disease. We analyzed 1907 patients who underwent allo-HSCT between 2010 and 2022, stratifying them into four fludarabine dose groups: 110-130 mg/m2, 140–150 mg/m2, 151–160 mg/m2, and 170–190 mg/m2. Our results suggest that a lower fludarabine dose (≤130 mg/m2) is associated with significantly improved leukemia-free survival (LFS), graft-versus-host disease-free/relapse-free survival (GRFS), overall survival, and reduced non-relapse mortality. Multivariate analysis shows that a lower fludarabine dose (≤130 mg/m2) was associated with significantly improved LFS (HR 1.46, 95% CI: 1.09–1.94) and GRFS (HR 1.50, 95% CI: 1.12–1.99). These findings indicate that using a lower fludarabine dosing in older AML patients may improve the efficacy and tolerability of allo-HSCT. Further studies are needed to validate these observations to confirm and expand upon our results, particularly in diverse patient populations and other indications for allo-HSCT.
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The datasets analysed during the current study are available from the corresponding author on reasonable request.
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GD, ML, MM designed the study, performed data analysis and interpretation, and wrote the manuscript; GS, CC, EF, IWB, PC, ED, DB, CEB, RV, AH, DB, JM, TS, JOB, BS, AS, FC took care of the patients and collected the data; all authors contributed to critical review and drafting of the manuscript.
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The ALWP review board approved the study protocol. This study was conducted in accordance with all relevant guidelines and regulations. Patients (or their legal guardians) provided informed consent authorizing the use of their personal information for research purposes.
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Dachy, G., Labopin, M., Socié, G. et al. Impact of fludarabine dose on outcome after allo-HSCT with reduced intensity conditioning for older patients with AML. Bone Marrow Transplant 60, 1258–1264 (2025). https://doi.org/10.1038/s41409-025-02614-1
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DOI: https://doi.org/10.1038/s41409-025-02614-1
