HLA Linked Regional Differences in Donor Selection: A 9-Year Study of the Swiss Registry

Abstract

Introduction: The large HLA diversity in worldwide populations is a major challenge for matched unrelated haematopoietic stem cell (HSC) donor searches. The impact of regional diversity on the effective HSC donor selection has not been documented so far for national registries.

Methods: The aim of the study was to analyse the 532 consecutive work-up (WU) requests received by Swiss Blood Stem Cells (SBSC), over a 9-year period (2011-2019) with respect to criteria including the geographical origin of the donors as derived from the postal codes, countries requesting SBSC donors, HLA-matching parameters, and patients' HLA haplotype frequencies.

Results: Highly matched donors (10/10) represented 73.5% of the WU, whereas 8-9/10 mismatched donors accounted for 24.0%. The remaining donors were 7-8/8 matched (1.7%) or had an unknown matching grade (0.8%). Among the 10/10 matched patient/donor pairs with full HLA-DPB1 typing information, the rate of 11-12/12 matched donors was 73.3%. Of the 532 WU requests, 47.6% were for patients of the four neighbouring countries and for national patients. The ratio of WU requests was directly proportional to the total number of donors registered in each region (Pearson's r = 0.977). However, for two regions (lemanic and north-eastern areas of Switzerland (CH)), the proportion of selected donors was slightly above the min-max ratio of registered donors throughout the study period. The number of WU requests differed between countries when considering donors from the northern and southern parts of the country delineated by the alpine barrier.

Conclusion: This study shows the value of the SBSC registry for both national and international patients. Two countries (USA and Germany) which operate the two worldwide largest registries (>19 million donors) requested 30% of SBSC registered donors, while the Swiss transplant centres accounted for 13% of the WU requests. When considering the geographic origin of SBSC donors, we observe a correlation of WU requests with the total number of registered donors in each subregion. This finding thus supports recruitment efforts throughout all regions. Interestingly, donors from three regions (lemanic area, Zurich and Ticino) are slightly over-represented, which is possibly related to higher HLA haplotypic diversity. A focus on planning recruitment in these regions might contribute to more successful donor searches.

Keywords: HLA haplotypes; Regional differences; Registry; Unrelated donors.