Donor-Specific Anti-HLA Antibodies in Allogeneic Hematopoietic Cell Transplantation: A Systematic Review of Donor Selection, Risk Stratification, and Desensitization

Preprint, not peer reviewed. Screening and data extraction were done by a single author; extracted study values have not been independently verified. Background: Donor-specific anti-HLA antibodies (DSA) are a recognized barrier to engraftment in HLA-mismatched allogeneic hematopoietic cell transplantation (allo-HCT). Management consists of selecting a donor that lacks the targeted antigen or, when this is not possible, antibody-directed desensitization, but published evidence is fragmented and DSA thresholds are not standardized. Objective: To systematically review clinical studies of DSA in allo-HCT, with emphasis on antibody characteristics, donor selection, desensitization, and engraftment outcomes. Study design: PubMed/MEDLINE was searched without date limits on 25 September 2026. Study selection followed PRISMA 2020. Risk of bias was appraised qualitatively, and results were synthesized narratively with each study’s original MFI threshold preserved. Results: Of 167 records screened, 38 primary studies were included, most of them retrospective cohorts of haploidentical transplantation. Higher DSA MFI and complement-binding DSA were repeatedly associated with primary graft failure or poor graft function, but thresholds varied between studies. Donor avoidance eliminated the antibody-donor mismatch when an alternative donor existed. In small series, multimodal desensitization was associated with DSA reduction and engraftment in most treated patients, while residual DSA, high MFI, and complement binding remained concerns. Conclusions: DSA management is best framed as an individualized donor-selection and antibody-risk problem rather than a search for a single superior desensitization regimen. The evidence is low in volume and mostly observational. Prospective comparative studies are needed.