HLA‐haplotype redundancy and rareness in Canadian Blood Services' Stem Cell Registry and Cord Blood Bank: Novel metrics for optimizing utility

Background The utility of unrelated donor registries that support allogeneic hematopoietic cell transplantation could be optimized through greater understanding of redundancy and rareness of HLA phenotypes. Methods HLA phenotype rareness was determined using known HLA haplotype frequencies. Donor redundancy was determined through pairwise comparison of donor HLA profiles within an inventory. Results Among 61,730 registrants in the Canadian Blood Services (CBS) Stem Cell Registry (SCR) with high resolution HLA typing at 5 loci, 6.6% of HLA phenotypes were redundant with variation across ethnic groups (8.3% of Caucasian phenotypes; 8% of Native American/First Nations, 4.4% of Asia‐Pacific Islanders (API), 2.1% of Hispanic, 0.7% of African‐American (AFA), and 4.5% of other ethnicities). A total of 18.5% of registrants had redundant HLA phenotypes with variation across ethnic groups. All 3716 cord blood units in the CBS's cord blood bank (CBB) had high resolution HLA typing at 5 loci and 202 units were redundant (5.4%) comprising 78 HLA phenotypes, with varying rareness. Repeated HLA phenotypes were from Caucasian donors (77%), multiple ethnicity (13%), API (9%), and AFA (1%). Registrants and CBUs with AFA ethnicity had the rarest phenotypes while Caucasian ethnicity was associated with the most common HLA phenotypes. Conclusions Redundancy was greater in the SCR compared to the CBB and was most common with CAU ethnicity. Recruiting non‐Caucasian registrants and continued cord blood banking should reduce redundancy. A sub‐inventory of redundant donors and cord blood units could support new uses for donor‐supported cellular therapies that do not require HLA matching.