Study Explores Link Between Allele Expression and Risk of Graft-vs-Host Disease in Transplant Recipients
In a study reported in The New England Journal of Medicine, Petersdorf et al found a greater risk of acute graft-vs-host disease among hematopoietic cell transplant recipients with the high-expression rs9277534G allele linked to mismatched HLA-DPB1 who received transplants from donors with the low-expression rs9277534A allele. It is known that risk of graft-vs-host disease is higher when recipient and donor are mismatched for HLA-DPB1, but the mechanisms of the increased risk have remained unclear.
Study Details
In the study, rs9277534 was genotyped in 3,505 persons to define rs9277534-DPB1 haplotypes. Clinical outcomes were assessed in 2,029 recipients of transplants from unrelated donors who were treated for acute leukemia, chronic myeloid leukemia, or myelodysplastic syndrome between 1988 and 2008 and who had data reported to the Center for International Blood and Marrow Transplant Research. Linkage of the rs9277534 A and G alleles to the mismatched HLA-DPB1 was determined among 1,441 recipients of transplants from HLA-A, B, C, DRB1, and DQB1-matched unrelated donors, with only one HLA-DPB1 mismatch. Risk of acute graft-vs-host disease was compared between recipients with the mismatched HLA-DPB1 allele linked to rs9277534G (high expression) vs recipients with the mismatched HLA-DPB1 allele linked to rs9277534A (low expression).
Risk of Acute Graft-vs-Host Disease
Overall, mean HLA-DPB1 expression was lower with rs9277534A than with rs9277534G.
Transplant recipients with rs9277534G-linked HLA-DPB1 mismatches had a higher risk of acute graft-vs-host disease (hazard ratio [HR] = 1.32, P < .001) but, consistent with graft vs leukemia effect, also had a lower risk of relapse (HR = 0.80, P = .04). Overall survival was similar for recipients with rs9277534G- vs rs9277534A-linked mismatches (HR = 1.03, P = 0.70).
Among recipients of transplants from donors with rs9277534A-linked HLA-DPB1, risk of acute graft-vs-host disease was higher for recipients with rs9277534G-linked HLA-DPB1 mismatches vs recipients with rs9277534A-linked mismatches (HR = 1.54, P < .001). Recipients with the rs9277534G-linked mismatch also had a higher risk of death due to causes other than disease recurrence (HR = 1.25, P = .05).
The investigators concluded, “The risk of graft-vs-host disease associated with HLA-DPB1 mismatching was influenced by the HLA-DPB1 rs9277534 expression marker. Among recipients of HLA-DPB1–mismatched transplants from donors with the low-expression allele, recipients with the high-expression allele had a high risk of graft-vs-host disease.”
The study was funded by the National Institutes of Health and others.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
