Outcomes of Haploidentical vs Mismatched Unrelated Donor HCT with Post-Transplant Cyclophosphamide Prophylaxis Open Access

• Donor age was a more consistently influential factor as a main effect, with a non-linear relationship with overall mortality hazard.

• The influence of donor type may be more complex, potentially becoming more pronounced in specific contexts, such as with older donors.

Limited data exist comparing haploidentical and mismatched unrelated donor (MMUD) hematopoietic cell transplantation (HCT) with post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease prophylaxis, especially considering donor age. Herein, we report the outcomes of 660 haploidentical and 195 MMUD HCT recipients treated at MD Anderson Cancer Center. Beyond standard Cox Proportional Hazards modeling, we employed inverse probability of treatment weighting (IPTW), matched-pair analysis, and performed additional analysis by incorporating an external MMUD validation cohort from the Center for International Blood and Marrow Transplant Research (CIBMTR). The primary outcome was overall survival (OS). In multivariable analysis, haploidentical donors had a hazard ratio of 1.20, with a 95% confidence interval (CI), 0.93-1.54, p=.16 compared to the MMUD group. Donor age showed a non-linear association with OS. These findings were corroborated by IPTW, matched-pair analyses, and CIBMTR validation analyses. Exploratory analysis revealed inferior OS for older (>50 years) haploidentical donor group compared to younger (<30 years) MMUD recipients (HR 1.91, 95% CI 1.21-3.01, p=.005). Our analyses suggest that while donor type may play a role, there was a more prominent role for donor age in influencing OS. Moreover, our findings indicate a potential nuance wherein the impact of donor type may vary by donor age. Further research, particularly with larger cohorts, is needed to fully elucidate the complex and potentially interacting roles of donor type and donor age, along with HLA factors.