Availability of HLA-allele-matched unrelated donors and registry size: Estimation from haplotype frequency in the Italian population

In Italy, an HLA-matched unrelated donor is currently the primary donor when a HLA matched sibling is not found for allogeneic haematopoietic stem cell transplantation (HSCT). Better outcomes for transplantation require optimal matching between donor and recipient at least at the HLA-A,-B,-C, and-DRB1 loci; therefore, the availability of HLA-matched unrelated donors is important. The enormous HLA polymorphism has always necessitated registries with a large number of individuals in order to be able to provide well-matched donors to a substantial percentage of patients. In order to increase the efficiency of the Italian Bone Marrow Donor Registry (IBMDR) in providing Italian patients with a suitable donor, the probability of finding an HLA-A,-B,-C, and-DRB1 allele-matched (8/8) or a single mismatch unrelated donor (7/8) was estimated in this study according to IBMDR size. Using a biostatistical approach based on HLA haplotype frequencies of more than 100,000 Italian donors enrolled in the IBMDR and HLA-typed at high resolution level, the probability of finding an 8/8 HLA-matched donor was 23.8%; 33.4%; and 41.4% in simulated registry sizes of 200,000; 500,000; and 1,000,000 donors; respectively. More than 2 million recruited donors are needed to increase the likelihood of identifying an HLA 8/8 matched donor for 50% of Italian patients. If one single mismatch at HLA I class loci was accepted, the probability of finding a 7/8 HLA-matched donor was 62.8%; 73.7%; and 80.3% in 200,000 donors; 500,000; and 1,000,000 donors; respectively. Using the regional haplotype frequencies of IBMDR donors, the probability of recruiting a donor with a new HLA phenotype, in the different Italian regions, was also calculated. Our findings are highly relevant in estimating the optimal size of the national registry, in planning a cost-effective strategy for donor recruitment in Italy, and determining the regional priority setting of recruitment activity in order to increase the phenotypic variability of IBMDR as well as its efficiency. (c) 2021 The Author(s). Published by Elsevier Inc. on behalf of American Society for Histocompatibility and Immunogenetics. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).

Automated summary

In Italy, the primary donor for allogeneic hematopoietic stem cell transplantation is currently an HLA-matched unrelated donor when a matched sibling is not found. The study suggests that recruiting over 2 million donors is needed to increase the likelihood of finding an 8/8 HLA-matched donor for 50% of Italian patients, and the probability of finding a 7/8 HLA-matched donor significantly increases if accepting one mismatch at HLA I class loci. Additionally, the probability of recruiting a donor with a new HLA phenotype in different Italian regions was also calculated based on regional haplotype frequencies.