Interplay between donor age and HLA-DP matching in 10/10 HLA-matched unrelated donor HCT

• Donor age should be prioritized over HLA-DPB1 matching in patients undergoing 10/10-HLA matched unrelated donor HCT

• HLA-DPB1 matching is associated with relapse and non-relapse mortality within younger, but not older, donor groups.

In 10/10 HLA-matched unrelated donor (MUD) hematopoietic cell transplantation (HCT) with calcineurin-inhibitor (CNI)-based prophylaxis, T-cell epitope DP-matched and permissive mismatched donors are associated with similar overall survival (OS) while donors with non-permissive mismatches should be avoided. Younger unrelated donors are also favored over older donors. We explored outcomes associated with different combinations of DP-matching and donor age (dichotomized at 35 years) to further guide donor selection. Using a Center for International Blood and Marrow Transplant Research dataset, we categorized 10,783 patients into six groups: DP-matched/younger donor (n=1591), DP-matched/older donor (n=526), permissive-mismatched/younger donor (n=3845), permissive-mismatched/older donor (n=1184), non-permissive mismatched/younger donor (n=2659), non-permissive mismatched/older donor (n=978). We noted that younger donor age, rather than DP-matching, was associated with better OS. Younger donors with permissive mismatches were associated with improved OS compared to older matched donors. Furthermore, younger donors with non-permissive mismatches were associated with improved OS compared to older donors with permissive mismatches. Our study adds further information about the association of DP-matching and donor age with HCT outcomes. Donor age should be prioritized over DP-matching in patients undergoing 10/10 HLA-MUD with CNI prophylaxis. Among those with younger donors, permissive-mismatched or DP-matched donors are preferred over non-permissive mismatched donors.