Serologic Characteristics and Clinical Significance of Non-ABO Red Blood Cell Antibodies in Hematopoietic Stem Cell Transplantation: The BEST Collaborative Study

ABO-incompatible hematopoietic stem cell transplantation (HSCT) has a number of well-established complications, including hemolysis, delayed RBC engraftment, pure red cell aplasia (PRCA), and transfusion dependence; however, the clinical significance of non-ABO RBC antibodies in allogeneic HSCT remains insufficiently explored. The present study aimed to characterize the prevalence, incidence, and clinical implications of non-ABO RBC autoantibodies and alloantibodies in the HSCT population. This international multicenter retrospective study analyzed HSCT 2010-2021 across 9 US and 1 Brazilian academic centers, focusing on immunohematologic findings in recipients of allogeneic HSCT, excluding hemoglobinopathies. RBC antibodies were evaluated pre-HSCT and at 100 days post-HSCT. Hemolysis was assessed by laboratory tests and confirmed by a 2-physician review of the medical records. Descriptive statistics and regression analysis were performed. IRB approval and data use agreements were obtained at each center. The study analysis included a total of 8896 transplants. The majority of transplantations used apheresis collection (78.0%), were matched unrelated (41.6%), involved a nonmyeloablative conditioning regimen (51.2%), and were ABO-compatible (56.7%). The prevalence of non-ABO antibodies pre-HSCT, including autoantibodies, alloantibodies, and passive transfer of anti-D, was 4.0% (n = 355). The majority of these were alloantibodies (77.5%), followed by warm autoantibodies (7.3%) and both alloantibodies and warm-reactive autoantibodies (6.5%). De novo antibody formation post-HSCT occurred in 1.5% (n = 135). The most frequent pre-HSCT alloantibody specificities were in the Rh blood group system (46%), followed by Kell (17%) and Kidd (13%). The incidence of anti-D in RhD-mismatched transplants was 1% (n = 8) for RhD-positive recipients with RhD-negative donors, and 0.2% (n = 2) for RhD-negative recipients with RhD-positive donors. Myeloproliferative neoplasms and myelodysplastic syndromes had the highest rate of antibodies pre- and post-HSCT. Hemolysis was observed in 24 cases (antibodies present pre-HSCT) and in 15 de novo cases post-HSCT. PRCA was not observed in any of these cases. The presence of non-ABO RBC antibodies was associated with higher RBC transfusions but not platelet transfusions; engraftment of neutrophils and platelets was not affected by the presence of RBC antibodies. The current study reports on a low prevalence of RBC antibodies, including alloantibodies and autoantibodies, in HSCT recipients during the peritransplantation period, with a rate of 4% for those with preexisting antibodies pretransplantation and 1% for de novo antibody formation post-transplantation. They are associated with a low risk of mild to moderate hemolysis but increased RBC transfusions. Comprehensive immunohematology data should be incorporated into HSCT databases for improved risk assessment, monitoring, and management.