The level of expression of mismatches, and in some cases, number of mismatches, of HLA-DPB1 were associated with an increased risk of developing graft-versus-host disease (GVHD) after unrelated hematopoietic cell transplant (HCT), according to results from a study published in the Journal of Clinical Oncology.
Previous studies have established that the HLA-DPB1 antigen can result in graft-versus-host and host-versus-graft allorecognition. The purpose of this study was to confirm the role of HLA-DPB1 expression in the development of GVHD in a large cohort of transplant recipients with varying degrees of antigen matching.
The analysis included data from 19,136 patients who underwent unrelated HCT between 1988 and 2016 from the International Histocompatability Working Group database. The cohort included 11,318 patients who were HLA-10/10, 5880 who were HLA-11/12 with 1 HLA-DPB1 mismatch, and 3391 who had 2 HLA-DPB1 mismatches.
The primary study endpoints were grade 2 to grade 4 (moderate) and grade 3 to grade 4 (severe) acute GVHD. Secondary endpoints included relapse, death not preceded by relapse, disease-free survival (DFS), and overall mortality.
Donor mismatching with 1 donor with a high expression of HLA-DPB1 with transplant recipients who were HLA-A, -B, -C, -DRB1, -and DQB1–matched compared with low-expression patient mismatches was significantly associated with increased odds of moderate (odds ratio [OR], 1.36; 95% CI, 1.19-1.54; P <.001) and severe (OR, 1.32; 95% CI, 1.11-1.57; P =.002) GVHD.
The expression level of the donor’s mismatched HLA-DPB1 was not associated with GVHD.
Acute GVHD was also significantly associated with increasing numbers of HLA-DPB1 mismatches among transplant recipients with 1 HLA-A, -B, -C, -DRB1, or -DQB1 mismatches. For moderate GVHD, the ORs were 1.23 (95% CI, 1.08-1.40; P =.002) for 1 mismatch and 1.40 (95% CI, 1.21-1.62; P <.001) for 2 mismatches; for severe GVHD, the ORs were 1.19 (95% CI, 1.01-1.40; P =.04) for 1 mismatch and 1.40 (95% CI, 1.18-1.67; P <.001) for 2 mismatches, compared with 0 mismatches. The level of expression of the mismatched HLA-DPB1 allotype was not associated with GVHD.
The authors concluded that, given these data, and “together with increasing ease of upfront HLA-DPB1 typing of patients and unrelated donors, the use of HLA-DPB1 expression in day-to-day clinical practice may enhance donor selection and lower GVHD risks for patients.”
Petersdorf EW, Bengtsson M, De Santis D, et al. Role of HLA-DP expression in graft-versus-host disease after unrelated donor transplantation [published online June 1, 2020]. J Clin Oncol. doi: 10.1200/JCO.20.00265