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Disease relapse occurs in unrelated cord blood transplantation (CBT) even when the alleles of human leukocyte antigen (HLA) are fully matched between donor and recipient. This is similar to that observed in other types of hematopoietic stem cell transplantation. Fourteen single nucleotide polymorphisms (SNPs) within the HLA region have been reported previously by Petersdorf et al. and Piras et al. as transplantation determinants in unrelated hematopoietic cell transplantation. In this study, the genomic sequences within 500 base pairs upstream and downstream of the fourteen transplantation-related SNPs from 53 patients and their HLA-matched unrelated donors were analyzed for determining whether or not genetic variants, conferred by either recipient or donor SNP genotype or by recipient-donor SNP mismatching, were associated with the risk of relapse. Seven SNPs were associated with the risk of relapse in unrelated CBT. These included the donor genotype with the SNPs of rs2523675 and rs2518028 at the telomeric end of HCP5 gene, rs2071479 in the intron of the HLA-DOB gene, and rs2523958 in the MICD gene; and the recipient genotype with SNPs of rs9276982 in the HLA-DOA gene, and rs435766 and rs380924 in the MICD gene. As measured by pair-wise linkage disequilibrium (LD) with  D ′ as the parameter for normalized standard measurement of LD which compares the observed and expected frequencies of one haplotype comprised by alleles at different loci, rs2523675 had high LD with rs4713466 ( D ′ = 0.86) and rs2523676 ( D ′ = 0.91) in the HCP5 gene. The rs2518028 had no LD with all other SNPs except rs2523675 ( D ′ = 0.76). This study provides the basis for developing a method or algorithm for selecting better unrelated CBT candidate donors.

Single nucleotide polymorphisms within HLA region are associated with disease relapse for patients with unrelated cord blood transplantation