Management of donor-specific antibodies in allogeneic hematopoietic cell transplantation: A retrospective single-center case-control study

Abstract

Donor-specific antibodies (DSA) are preformed recipient antibodies directed against donor HLA antigens, most frequently observed in haploidentical or mismatched allogeneic hematopoietic cell transplantation (HCT). DSA assessed by multiplexed bead-based immunoassays at mean fluorescence intensity (MFI) values >1 000 are associated with increased risk of graft failure, graft-versus-host disease (GvHD), and mortality, supporting combined pharmacological and plasma-based depletion in absence of matching donors. We retrospectively analyzed all adult HCTs performed between 2009 and 2025 at the University Hospital Tübingen, Germany, with clinically relevant DSA (MFI >1 000). Assessments included depletion strategies, engraftment, GvHD, overall survival, and immune reconstitution. A 2:1 matched control cohort without DSA was selected based on disease, age, sex, and donor features. Fourteen cases were identified (1.2% of all transplants; 9.1% of haploidentical procedures). Depletion regimens included rituximab (n=12), bortezomib (n=10), daratumumab (n=2), intravenous immunoglobulins (n=6), plasma exchange (n=8), and immunoadsorption (n=9). MFI reduction <1 000 before HCT was achieved in 5 of 11 evaluable patients. All but two recipients engrafted timely; both graft failures occurred after single-modality depletion. Clinical outcomes did not differ significantly between DSA patients and controls. These real-world data underscore the importance of systematic DSA screening and multimodal depletion to optimize transplantation outcomes.