Allelic and haplotypic HLA frequency distribution in Spanish hematopoietic patients. Implications for unrelated donor searching

Abstract

Histocompatibility criteria for unrelated donor selection are based on high-resolution definition of HLA genes. In spite of the expansion of the unrelated donor registries, HLA matching remains a problem for many patients because of the great diversity of HLA alleles and haplotypes. The availability of matched donors at an allelic level depends on the frequency of the patient's alleles and haplotypes. Therefore, data regarding HLA distribution for each population are needed in order to evaluate the donor searching approach and, may be, even the therapeutic strategy. In the present report, we have analyzed 253 haematological Spanish patients awaiting unrelated haematopoietic stem cell (HSC) donors. HLA allele and haplotype frequencies have been defined at high resolution for the first time in this population. Significant differences in HLA distribution have been reported when comparing two patient groups, one that received full-match (10/10) unrelated donors and one that did not. Factors like rare alleles, presence of B*510101 (because of the association with multiple HLA-C alleles), as well as infrequent B-C and DRB1-DQB1 associations, showed a negative value for finding a suitable donor, whereas the presence of one of the six-gene haplotypes with a frequency ≥ 0.9% in our sample was a positive factor influencing donor searching. These differences will be useful in donor searching advising and in the use of different therapeutic strategies.