Transplant Outcomes Using Older Matched Sibling Donors Compared to Young Alternative Donors: A CIBMTR Analysis.

Whether younger donors should be prioritized over HLA-matching for allogeneic hematopoietic cell transplantation (allo-HCT) when using post-transplant cyclophosphamide (PTCy)-based graft versus host disease (GvHD) prophylaxis is unclear. To address this, we compared outcomes of allo-HCT recipients aged ≥50-years using PTCy-based GvHD prophylaxis from an older (≥50-years) matched sibling donor (MSD) to those of younger alternative donors ≤35-years: HLA-matched unrelated donors (MUD), HLA-mismatched unrelated donors (MMUD), and haploidentical (haplo)-related donors reported to the Center for International Blood & Marrow Transplant Research between 2014-2021. Young MUD and older MSD receiving calcineurin inhibitor (CNI)-based allo-HCT that met study criteria were concurrently examined. The primary endpoint was overall survival (OS). Among 14,662 HCT recipients, 3,746 received PTCy- and 10,916 CNI-based GvHD prophylaxis. The median follow-up was 47 months. In patients treated with PTCy, the adjusted 5-year OS was not significantly different at 44% for MSD compared with 52% for MUD (multivariable hazard ratio [HR]: 1.20, 95%CI: 1.03-1.41, p=0.09), 45% for haplo (HR: 1.02, 0.88-1.18, p=1.00) and 46% for MMUD (HR: 1.00, 0.83-1.21, p=1.00). Compared to MSDs, receipt of younger MUD associated with improved disease-free survival (DFS) both with PTCy (HR: 1.21, 1.05-1.40, p=0.048) and CNI (HR 1.09, 1.04-1.15, p<0.01) based prophylaxis. Haplo-donor recipients associated with similar OS to MSD, but worse OS compared to MUD recipients with PTCy (HR: 1.18, 1.05-1.33, p=0.04). These data suggest that older MSDs result in similar OS compared to younger alternative donors in older-aged recipients. Younger MUDs may be preferred for older patients due to improved DFS when available.