HLA-DPB1 TCE mismatch vector differentially affects HCT outcomes in 10/10 and ≤9/10 HLA matched patients in the UK
In brief
Bi-directional HLA-DPB1 mismatches worsen five-year outcomes in fully matched transplants
In a UK cohort of 1,743 unrelated donor hematopoietic cell transplants, patients with 10/10 HLA matching who received bi-directional HLA-DPB1 non-permissive mismatches had significantly lower overall survival and higher transplant-related mortality than those with matched or permissive mismatches. By contrast, host-versus-graft HLA-DPB1 mismatches improved survival in partially matched recipients, suggesting that mismatch direction should guide donor selection, but further validation is needed.
- Journal
- Transplantation and cellular therapy (Q1)
- Published
- 18 September 2026
- Study design
- Retrospective cohort
- Evidence level
- Level 3, Low (CEBM 3b)
- Authors
- Thomas R Turner, Charlotte A Cambridge, Jonathan A M Lucas, Albert J E French, Shelley Hewerdine, Diana F Voiniciuc, et al.
- PMID
- 42759663
- DOI
- 10.1016/j.jtct.2026.09.033
Why clinicians should know about it
- Picked for Transplantation (paper of the day, 21 September 2026): HLA‑DPB1 TCE mismatch impact on HCT outcomes
Abstract
BACKGROUND: Understanding permissive and beneficial HLA mismatches is a primary area of hematopoietic cell transplant (HCT) research. HLA-DPB1 is well studied in this context, due to its separation from HLA-A∼DQB1 by a recombination hot-spot. OBJECTIVES: The primary study aim was to retrospectively assess the clinical impact of using the latest iteration of the HLA-DPB1 T cell epitope model (TCEv3) for selecting HLA-DPB1 mismatched donors in a UK cohort. The results were also compared to the previous, TCEv2 model. STUDY DESIGN: We used the TCEv3 model to assign core and non-core permissive mismatches, to a cohort of 1743 UK volunteer unrelated donor HCTs for malignant diseases between 1996 and 2020. We considered HLA-DPB1 mismatch vector (graft versus host (GvH), host versus graft (HvG), and bi-directional (Bi-D)) across TCE groups, and existing HLA-A∼DQB1 mismatching. RESULTS: In 10/10 HLA matched patients, Bi-D HLA-DPB1 non-core permissive/non-permissive mismatches were associated with significantly worse 5-year overall survival, transplant related mortality, progression-free survival, chronic graft versus host disease (GvHD) and GvHD-free, relapse-free survival (GRFS) compared to HLA-DPB1 matched/permissively mismatched patients. In ≤9/10 HLA matched patients, both Bi-D and HLA-DPB1 matched/permissive mismatches were associated with similarly poor survival, while HvG HLA-DPB1 mismatches reduced mortality and improved GRFS. Overall risk of grades 2-4 acute GvHD (aGvHD) increased with the presence of GvH HLA-DPB1 mismatches and HLA-A∼DQB1 mismatching. CONCLUSIONS: Assessing mismatch vector revealed that some canonical non-permissive HLA-DPB1 mismatches are equivalent to an HLA-DPB1 match/permissive mismatch and can be beneficial. Similarly, some canonical permissive mismatches and, surprisingly, HLA-DPB1 matching in an already mismatched setting were detrimental. Bi-D HLA-DPB1 mismatched patients consistently had the poorest outcomes. This UK first, multicenter study shifts our understanding of HLA-DPB1 permissibility in UK HCT, with potential to improve patient survival and quality of life post-HCT through alternative donor selection.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.