Case Report: Allogeneic hematopoietic stem cell transplantation in a patient with triple-allele expression at both HLA-B and HLA-C loci

Yoshiyuki Fujita¹Kyoko Yoshihara^1*Daisuke Takahashi²Hidenori Tanaka³Yusuke Kino³Fuyuki Yamagata¹Mami Samori¹Saki Takahashi¹Satoshi Yoshihara^1*

• ¹Hyogo Medical University, Kobe, Japan
• ²Japanese Red Cross Society Blood Service Headquarters Central Blood Research Institute, Tokyo, Japan
• ³HLA Laboratory, Kyoto, Japan

Background: Human leukocyte antigen (HLA) matching is critical for donor selection in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Each HLA locus is normally biallelic; however, exceptionally rare cases with more than two alleles at a single locus have been reported. Case presentation: We describe a 17-year-old male with mixed phenotype acute leukemia (T/myeloid) who was found to carry three alleles at both the HLA-B and HLA-C loci during pre-transplant evaluation. Family-based HLA typing revealed that the additional alleles were inherited as part of a single maternal haplotype shared by multiple siblings. Flow cytometric analysis using antisera with known HLA specificity demonstrated that all three HLA-B and HLA-C alleles were expressed on the cell surface. Because this unusual immunogenetic configuration precluded the identification of an unrelated donor, a sibling donor sharing the same triple-allele haplotype was selected despite a single HLA-A mismatch. Allo-HSCT was successfully performed, with manageable graft-versus-host disease. Conclusion: This case highlights an extremely rare immunogenetic configuration in which triple-allele expression at two HLA class I loci directly influenced donor selection for allo-HSCT. Comprehensive interpretation of HLA typing results, including family analysis and protein-level expression, is essential when such atypical findings are encountered.