Hematopoietic Cell Transplantation Outcomes in the Era of Post-Transplant Cyclophosphamide: Comprehensive Donor Analysis

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Donor types influence outcomes after allogeneic hematopoietic cell transplantation (HCT), but their relative impact in the post-transplant cyclophosphamide (PTCy) era is uncertain. We performed a multicenter retrospective cohort study using Center for International Blood and Marrow Transplant Research data for adults with acute leukemia or myelodysplastic syndromes undergoing first HCT from matched sibling donors (MSD), 8/8 matched unrelated donors (MUD), 7/8 mismatched unrelated donors (MMUD), or haploidentical donors between 2017 and 2023 with PTCy-based graft-versus-host disease (GVHD) prophylaxis. The primary cohort included 12,617 patients: 1,263 MSD, 4,117 MUD, 1,426 MMUD, and 5,811 haploidentical recipients. In multivariable models adjusted for donor age and clinical covariates, overall survival (OS) was lower with MUD (hazard ratio [HR], 1.16; 95% CI, 1.00-1.34, p=0.004), MMUD (HR, 1.32; 95% CI, 1.12-1.55, p<0.001), and haploidentical donors (HR, 1.43; 95% CI, 1.24-1.64, p<0.001) compared with MSD. GVHD-free, relapse-free survival (GRFS) was similar for MUD and MSD (reference) but lower with MMUD and haploidentical donors. Compared to MSD, all other donor groups had lower relapse risk but higher non-relapse mortality and acute GVHD, with similar chronic GVHD. In sensitivity analyses excluding donor-age adjustment, compared to MSD, OS was similar for MUD and MMUD, and GRFS was improved with MUD and similar for MMUD and haploidentical donors. These findings suggest that PTCy narrows outcome differences across donor types, shifting donor selection from rigid hierarchies and supporting timely HCT using the best available donor.