UC Davis Health System, Sacramento, CA, USA Sacramento, California, United States
Background/Case Studies: Donor-specific anti-HLA antibodies (DSAs) are a well-established risk factor for primary graft failure and decreased overall survival in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). With increasing use of mismatched unrelated donors (MMUD) and advances in anti-HLA antibody detection, effective DSA management has become increasingly important. While reducing DSA levels prior to transplant is associated with improved engraftment outcomes, the optimal desensitization approach remains uncertain. Desensitization strategies, aimed to remove circulating DSAs and/or decrease antibody production, include therapeutic plasma exchange (TPE), rituximab, IVIG and transfusion of antigen positive platelets. These strategies are typically used in various combinations.
Study
Design/Methods: Retrospective case report.
Results/Findings: A 20-year-old female with aplastic anemia was scheduled for a myeloablative allo-HSCT from a MMUD. Pre-transplant evaluation revealed donor-specific anti-HLA-A24 antibodies with a mean fluorescent intensity (MFI) of 5388, indicating high strength. She underwent two sessions of TPE, reducing the MFI to 2243. To further lower antibody levels, she was transfused with three units of HLA-A24–positive platelets. This led to a subsequent MFI drop to 1325, and by days 3 and 7 post-transfusion, anti-HLA-A24 antibodies were undetectable (Fig. A). While prior reports of antigen-positive platelet use often included B-cell–targeted therapy such as rituximab to mitigate amnestic responses, this case demonstrates that, in the context of myeloablative conditioning, targeting B cell therapy may not be necessary.
Conclusions: This case highlights the potential role of HLA antigen–positive platelet transfusion, in combination with therapeutic plasma exchange and myeloablative chemotherapy, as an effective desensitization strategy for moderate to high intensity MFI DSAs in allo-HSCT. Notably, the absence of B-cell–directed therapy did not result in an amnestic response, suggesting that conditioning intensity may influence the need for additional immunomodulation. Further studies are needed to standardize desensitization protocols in this setting.