In a study reported in the Journal of Clinical Oncology, Petersdorf et al found that level of expression of patient HLA-DPB1 mismatches and number of mismatches affect risk of acute graft-vs-host disease (GVHD) after unrelated donor hematopoietic cell transplantation.
“Prospective consideration of HLA-DPB1 may help to lower GVHD risks after transplantation.”— Petersdorf et al
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Study Details
The study involved data on 19,136 patients who received hematopoietic cell transplantation from an HLA-A, -B, -C, -DRB1, -DQB1–matched or –mismatched unrelated donor between 1988 and 2016. Data were contributed to the International Histocompatibility Working Group in Hematopoietic Cell Transplantation by transplant centers and registries in Australia, the European Union, Japan, North America, and the United Kingdom. Among transplant recipients with one HLA-DPB1 mismatch, the mismatched HLA-DPB1 allotype was defined as low or high expression.
Analyses were adjusted for year, conditioning regimen, disease status, cytomegalovirus serostatus, patient age, donor age, stem cell source, donor sex, patient sex, use of total body irradiation, use of T-cell depletion, patient race, donor race, mean HLA-C expression, patient HLA-B leader genotype, and mean HLA-A expression.
Key Findings
In HLA-A, -B, -C, -DRB1,-DQB1–matched transplant recipients, donor mismatching against one high-expression patient HLA-DPB1 vs low-expression patient mismatches was associated with increased risk of moderate (odds ratio [OR] = 1.36, P = .001) and severe acute GVHD (OR = 1.32, P = .0016) irrespective of the donor’s mismatched HLA-DPB1 expression level.
Among recipients with one HLA-A, -B, -C, -DRB1, or -DQB1 mismatch, risk of acute GVHD increased with increasing numbers of HLA-DPB1 mismatches but not with the level of expression of the patient’s mismatched HLA-DPB1 allotype. Compared with no mismatches, odds ratios were 1.23 (P = .002) for one mismatch and 1.40 (P < .001) for two mismatches for moderate acute GVHD, and 1.19 (P = .04) for one mismatch and 1.40 (P < .001) for two mismatches for severe acute GVHD.
The investigators concluded, “The level of expression of patient HLA-DPB1 mismatches informs the risk of GVHD after HLA-A, -B, -C, -DRB1, -DQB1–matched unrelated hematopoietic cell transplantation, and the total number of HLA-DPB1 mismatches informs the risk of GVHD after HLA-mismatched unrelated hematopoietic cell transplantation. Prospective consideration of HLA-DPB1 may help to lower GVHD risks after transplantation.”
Effie W. Petersdorf, MD, of the University of Washington, Fred Hutchinson Cancer Research Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by National Institutes of Health grants, U.S. Office of Naval Research grants, Swiss FNRS and Philanthropy Settlement Foundation, and others. For full disclosures of the study authors, visit ascopubs.org.
