A European HLA Isolate and Its Implications for Hematopoietic Stem Cell Transplant Donor Procurement

Abstract

Europeans have often been considered a homogenous group in registry donor match predictions, but it is now evident that HLA haplotype frequencies vary across the European continent. Earlier studies have indicated that Finns in northeastern Europe have unique HLA characteristics, and the increasing availability of high-resolution registry donor data is now making more detailed comparisons possible. In the first phase of the present study, estimated HLA haplotype frequencies in stem cell donor registries of Finland and its neighbors Sweden and Russia were calculated using the algorithm of the German National Bone Marrow Donor Registry (ZKRD) and their frequencies were compared with one another and also with that of Germany. Virtual donor searches for 1492 high-resolution typed Finnish patients in the Finnish, Swedish and German registries were then performed, using individual match predictions for each registry. In the last phase, the impact of specifically Finnish-enriched HLA haplotypes on Finnish patients and the use of Finnish registry donors was assessed by analyzing 647 consecutive hematopoietic stem cell transplantation (HSCT) donor searches and 40 exported Finnish HSCTs. The Finnish HLA landscape was more homogenous than the 3 other studied populations, but also genetically distinct from them. The match predictions found a probable 10/10 match for 71%, 41%, and 31% of the Finnish patients in the German, Finnish, and Swedish registries, respectively. Thirty-four of Finland's 100 most frequent HLA haplotypes were represented with a frequency of <.0003 in Germany, and with an 8- to 3262-fold greater frequency in Finland than in Germany. Patients carrying these Finnish-enriched haplotypes were less likely to receive a matched HSCT but more likely to receive it from a domestic donor. Registry donors carrying them were more likely to donate stem cells, both nationally and internationally. The Finnish HLA isolate has a significant impact on both Finnish patients and registry donors, explaining the high use of national registry donors for Finnish patients. Haplotype frequency estimations are an important tool for small registries as well, to help optimize donor match predictions and the size of individual registries.