The influence of HLA polymorphism and recombination events on the selection of a donor for hematopoietic stem cell transplantation
AbstractBackground: HSC transplantation outcome is associated with the level of HLA matching between donor and recipient. A search for HSC donor starts in the patient’s family. In the absence of related donor, HLA matched unrelated donors are searched in registries. In the present study we sought to determine the number of donors found in Slovenian families and the influence of initial typing and HLA polymorphism on the selection of unrelated donors. Patients and methods: We set up genotypes in 744 families that were typed for HLA-A, B, DR with PCR-SSP. Recombination events were located in 17 of them. Average number of children and percentages of possible related donors per year were calculated. SBT of HLA-A, B, C, DR, DQ alleles was performed for 162 patient/unrelated donor pairs. An influence of initial typing level on the selection of the donor was defined using Fischer’s exact test. A Slovenian population sample consisting of 77 unrelated individuals was typed for HLA-C using PCR-SSO and PCR-SSP methods. Phenotype frequencies were determined by direct counting. Results: Recombination was observed in 2.28 % of families. Among all patient/donor pairs matched after the initial phase, only 49.4 % remained HLA compatible after confirmatory typing. In particular, 38 % of the pairs were mismatched only owing to disparity at HLA-C. Conclusions: Lower percentage of related HLA identical donors is a consequence of decreasing number of children and occurrence of recombination events in families. Disparities at HLA-C were observed as a result of high level of polymorphism and initial typing not including this locus. This leads to the conclusion that the addition of HLA-C to the initial typing would contribute to faster and more efficient identification of well-matched stem cell donors, which is in most cases crucial for patient survival.
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