Value of Genetically Rare Cord Blood Units Beyond Conventional Quality Metrics

Allogeneic haematopoietic stem cell transplantation (HSCT) is a cornerstone therapy for haematological and genetic disorders. Owing to the limited availability of HLA-identical related donors, umbilical cord blood (UCB) has become a valuable alternative source of haematopoietic progenitors. However, many UCB units are excluded from banking based on quality criteria, despite potentially harbouring rare and underrepresented HLA profiles, particularly within certain demographic groups. This study evaluated the strategic value of immunogenetically rare but low-quality UCB units in expanding donor options for patients with uncommon HLA profiles. HLA-A, -B, and -DRB1 typing was performed on 577 UCB units, and allelic, haplotypic, and genetic diversity analyses were conducted using the HLA-net GENE[RATE] tool. Units were categorised using the Search Prognosis Application as good (6/6), fair (5/6), or poor (< 5/6 matches). Genotype frequency was used as a proxy for immunogenetic rarity and evaluated as an operational criterion for defining retention thresholds. ROC analyses were interpreted as concordance analyses between genotype frequency and Search Prognosis classification rather than as independent predictive validation. Statistical significance was assessed by chi-square and residual analyses. The cohort displayed remarkable allelic diversity, particularly at the HLA-B locus, strong linkage disequilibrium among loci, and a large proportion of unique genotypes. Matching-prognosis classification identified 66.72% of units as good, 31.54% as fair, and 1.73% as poor. Caucasian genotypes were overrepresented in the good category, whereas Asian-Pacific-Islander and African-American haplotypes were enriched in poorer matching-prognosis categories. ROC analysis showed strong concordance between genotype frequency and Search Prognosis classification (AUC 0.80-0.99) and population-specific genotype frequency thresholds. Our findings suggest that immunogenetic rarity provides complementary value to conventional quality metrics. While low-cell-dose units may have limited direct clinical utility, those with rare HLA genotypes may retain strategic importance, particularly for patients with uncommon immunogenetic profiles. Integrative approaches combining biological and immunogenetic parameters may improve cord blood banking strategies.