Mitigating HLA Disparity in AML Transplantation: Comparable Outcomes After Haploidentical and 9/10 Mismatched Unrelated Donor Transplantation With Treosulfan and PTCy

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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative strategy for acute myeloid leukemia (AML), but the impact of HLA disparity in the era of posttransplant cyclophosphamide (PTCy) and reduced-toxicity conditioning remains unclear. We performed an EBMT registry study including 275 adult AML patients in first complete remission undergoing first allo-HSCT between 2012 and 2023 using a uniform platform of treosulfan-based conditioning and PTCy. Among them, 206 received haploidentical grafts and 69 underwent 9/10 mismatched unrelated donor (MMUD) transplantation. Median follow-up was 2.5 years. At 2 years, overall survival was 73.1% after haploidentical transplantation and 71.6% after MMUD transplantation (p = 0.96). Leukemia-free survival at 1 year was 66.3% and 65.2%, respectively (p = 0.76). Relapse incidence (17.1% vs. 18.7%, p = 0.84) and nonrelapse mortality (16.6% vs. 16.1%, p = 0.86) were comparable between groups. Rates of Grade II-IV and Grade III-IV acute GVHD were similar, whereas chronic GVHD was higher after haploidentical transplantation (36.4% vs. 12.7%, p = 0.001), without differences in extensive forms. In multivariable analyses, donor type was not associated with overall survival, leukemia-free survival, relapse incidence, or nonrelapse mortality. Increasing age adversely affected outcomes, while Karnofsky performance status ≥ 90 and reduced-intensity conditioning were associated with improved survival. These findings suggest that, within a treosulfan-PTCy platform, major transplant outcomes are comparable between donor types, although haploidentical transplantation was associated with a higher incidence of chronic GVHD.

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