Red blood cell alloimmunization after hematopoietic stem cell transplant: Clinical challenges and implications for...

Alloimmunization against red blood cell (RBC) antigens is an uncommon but clinically significant complication following allogeneic hematopoietic stem cell transplantation (HSCT). While ABO and Rh incompatibilities are often considered in donor selection, other RBC antigens are rarely assessed.

We report the case of a 50-year-old male with high-risk acute myeloid leukemia who underwent unrelated HSCT. Over 2 years posttransplant, the patient developed an anti-U alloantibody, despite a previously U-positive phenotype. Immunohematological investigations revealed a posttransplant acquisition of a U-negative phenotype, confirmed by GYPB gene deletion and full donor chimerism. The donor was subsequently genotyped and confirmed to carry the same rare genotype. This alloimmunization posed transfusion challenges and required the identification of compatible U-negative RBC units for surgery.

To our knowledge, this is the first reported case of post-HSCT anti-U alloimmunization resulting from donor-derived RBC antigen mismatch. The case highlights the limitations of current donor screening protocols, the transfusion risks posed by high-frequency antigen incompatibilities, and the ethical considerations regarding the disclosure of genetic findings to unrelated donors.

This case highlights the need for comprehensive immunohematological assessment in HSCT, particularly when rare phenotypes may be involved, and calls for clearer guidelines on communication between transplant centers and donor registries regarding clinically relevant genetic findings.