Matched Unrelated vs Haploidentical Donor Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide.

Post-transplant cyclophosphamide (PTCy)-based graft-vs-host disease (GVHD) prophylaxis is the new standard for matched unrelated donor (MUD) hematopoietic cell transplantation (HCT). Prior studies comparing MUD and haploidentical donor HCT using PTCy were limited by size and short follow-up. We therefore performed a registry-based analysis examining the impact of donor type on HCT with PTCy. Adult patients (n=5,873) who received MUD (n=1,973) or haploidentical (n=3900) HCT with PTCy for acute leukemia (74.2%) or myelodysplastic syndrome (25.8%) reported to the CIBMTR between 2017- 2021 were included. Primary endpoints were three-year overall survival (OS) and GVHD-free, relapse-free survival (GRFS). Cox regression and sensitivity analyses were performed through adjustment of propensity scores. Haploidentical HCT had worse OS (Hazard ratio [HR] 1.15, 95% confidence interval [CI] 1.04-1.27, p=0.005) and GRFS (HR 1.19, 95% CI 1.10-1.29, p<0.001) compared to MUD HCT. Donor age was the only other consistent donor-related factor associated with survival. Results were confirmed in a sensitivity analysis adjusted for propensity scores. When the cohort was restricted to reduced intensity conditioning only or donors <30 years-old, OS did not differ between groups. Haploidentical HCT was associated with higher primary graft failure (HR 1.67; p=0.002), increased grade III-IV acute GVHD (HR 1.28; p=0.039), higher moderate/severe chronic GVHD (HR 1.47; p<0.001) and non-relapse mortality (HR 1.34; p<0.001). Grade II-IV aGVHD and relapse risk did not differ between the donor types. This large analysis showed that in adults with acute leukemia or MDS, MUD HCT was associated with improved outcomes compared to haplo HCT with PTCy-based GVHD prophylaxis.