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Impact of donor selection in adverse-risk AML undergoing hematopoietic cell transplantation: A study from the EBMT Acute Leukemia Working Party

Abstract

We evaluated the influence of donor type in 3006 adults with adverse-risk cytogenetic acute myeloid leukemia (AML) in first complete remission undergoing allogeneic hematopoietic cell transplantation (HCT). Donor types included matched sibling (MSD), matched unrelated (MUD), mismatched unrelated (MMUD), and haploidentical donors. At 2 years, leukemia-free survival, overall survival (OS), and graft-versus-host disease (GVHD)-free/relapse-free survival were 47%, 55%, and 36%. Compared with MSD, OS was inferior with MUD (HR 1.36; 95% CI, 1.1–1.67), MMUD (HR 1.4; 95% CI, 1.07–1.83), and haploidentical grafts (HR 1.33; 95% CI, 1.02–1.73). Haploidentical was associated with lower relapse risk (HR 0.72; 95% CI, 0.53–0.97), but higher non-relapse mortality (NRM) (HR 3.85; 95% CI, 2.44–6.08). All alternative donors showed higher rates of grade II–IV acute GVHD. In 702 patients receiving post-transplant cyclophosphamide (PTCy), survival differences attenuated. However, haploidentical and MMUD showed higher risk of grade III–IV acute GVHD (HR 2.61; 95% CI, 1.04–6.54 and HR 3.74; 95% CI, 1.14–12.24), and haploidentical had increased NRM (HR 3.22; 95% CI, 1.23–8.44), without significant relapse. Findings support safety of alternative donors and reinforce MSD as preferred choice in adverse-risk AML. PTCy mitigates but does not eliminate the risk of donor mismatch.

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Fig. 1: Cumulative incidence (CI) of graft-versus-host disease (GVHD) according to donor type.
Fig. 2: Cumulative incidence (CI) of main transplant outcomes according to donor type.
Fig. 3: Cumulative incidence (CI) of graft-versus-host disease (GVHD) according to donor type in the PTCy cohort.
Fig. 4: Cumulative incidence (CI) of main transplant outcomes according to donor type in the PTCy cohort.

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Data availability

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

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Authors

Contributions

M.V. and J.S. designed the study; A.F. performed statistical analysis and interpreted the results; M.V. and J.S. wrote the manuscript; A.F., T.G., G.S., A.H., I.W.B., I.Y., D.B., M.E., E.F., R.F., J.P., C.C., M.S., F.S., N.K., H.S., P.C., H.L., X.P., J.E., B.S., A.N., S.P., M.M., and F.C. provided patient data through the EBMT registry; and all authors reviewed and approved the manuscript.

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Correspondence to Marta Villalba.

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The scientific board of the ALWP of EBMT approved this study. All patients gave written informed consent for the use of their data.

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Villalba, M., Ferhat, AT., Gedde-Dahl, T. et al. Impact of donor selection in adverse-risk AML undergoing hematopoietic cell transplantation: A study from the EBMT Acute Leukemia Working Party. Bone Marrow Transplant 61, 187–196 (2026). https://doi.org/10.1038/s41409-025-02751-7

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