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

• Published in: Human immunology 2021-10, Vol.82 (10), p.758-766
• Main Authors: Sacchi, N., Ciceri, F., Bonifazi, F., Algeri, M., Gallina, A., Pollichieni, S., Raggio, E., Hadj-Amar, B., Lombardini, L., Pupella, S., Liumbruno, G., Cardillo, M.
• Format: Article
• Language: English
• Subjects: Algorithms; Alleles; Donor- patient matching; Gene Frequency; Genetics, Population; Haplotype frequency; Haplotypes; Hematopoietic Stem Cell Transplantation; Histocompatibility Testing - methods; HLA alleles; HLA Antigens - genetics; Humans; Italy; Likelihood Functions; Matching probability; Models, Theoretical; Probability; Registries; Tissue Donors; Unrelated donor registry; Unrelated Donors
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2021.07.012

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.