The following is a summary of “Impact of the HLA Immunopeptidome on Survival of Leukemia Patients After Unrelated Donor Transplantation,” published in the May 2023 issue of Oncology by Crivello, et al.

For a study, researchers sought to evaluate the impact of immunopeptidome divergence on T-cell alloreactivity and clinical outcomes in single-class I HLA-mismatched unrelated donor hematopoietic cell transplantation (UD-HCT) for acute leukemia or myelodysplastic syndromes.

The study analyzed 2,391 single class I HLA-mismatched and 14,426 fully HLA-matched UD-HCT performed between 2008 and 2018. Peptide-binding motifs (PBM) were used to cluster HLA-A, -B, or -C disparities based on immunopeptidome divergence. Of the HLA-mismatched UD-HCT, 1,629 (68.1%) were classified as PBM-matched or PBM-mismatched. Risks associated with PBM-matching status were assessed using Cox proportional hazards models, with overall survival (OS) as the primary endpoint.

Bidirectional or unidirectional PBM-GVH mismatches in graft-versus-host direction (60.7%) were associated with significantly lower OS (HR, 1.48; P < .0001), while unidirectional PBM mismatches in host-versus-graft direction or PBM matches (39.3%) were not (HR, 1.13; P = .1017). PBM-GVH mismatches also had significantly lower OS than PBM-GVH matches (HR, 1.32; P = .0036). The hazards for transplant-related mortality and acute and chronic graft-versus-host disease but not relapse increased stepwise from full HLA matches to single PBM-GVH matches and single PBM-GVH mismatches. A web tool for PBM-matching single class I HLA-mismatched donor-recipient pairs were developed.

Immunopeptidome divergence between mismatched HLA in single class I HLA-mismatched UD-HCT determines T-cell alloreactivity and clinical outcomes. Prospective consideration of directional PBM-matching status may improve outcomes in these cases. The study findings provided valuable insights into the role of immunopeptidome divergence in UD-HCT.

Source: ascopubs.org/doi/full/10.1200/JCO.22.01229