Effect of nonpermissive HLA-DPB1 mismatches after unrelated allogeneic transplantation with in vivo T-cell depletion.

Abstract

We investigated the impact of donor-recipient HLA-DPB1 matching on outcomes of allogeneic hematopoietic stem cell transplantation with in vivo T-cell depletion using antithymocyte globulin (ATG) for patients with hematological malignancies. All donor-recipient pairs had high-resolution typing for HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1, HLA-DPB1, and HLA-DRB3/4/5 and were matched at HLA-A, HLA-B, HLA-C, and HLA-DRB1. HLA-DPB1 mismatches were categorized by immunogenicity of the DPB1 matching using the DPB T-cell epitope tool. Of 1004 donor-recipient pairs, 210 (21%) were DPB1 matched, 443 (44%) had permissive mismatches, 184 (18%) had nonpermissive mismatches, in graft-versus-host (GVH) direction, and 167 (17%) had nonpermissive mismatches in host-versus-graft (HVG) direction. Compared with HLA-DPB1 permissive mismatched pairs, nonpermissive GVH mismatched pairs had the highest risk for grade II to IV acute graft-versus-host disease (aGVHD) (hazard ratio [HR], 1.4; P = .01) whereas matched pairs had the lowest risk (HR, 0.5; P < .001). Grade III to IV aGVHD was only increased with HLA-DPB1 nonpermissive GVH mismatched pairs (HR, 2.3; P = .005). The risk for disease progression was lower with any HLA-DPB1 mismatches, permissive or nonpermissive. However, the favorable prognosis of HLA-DPB1 mismatches on disease progression was observed only in peripheral blood stem cell recipients who were in the intermediate-risk group by the Disease Risk Index (HR, 0.4; P = .001) but no other risk groups. Our results suggest avoidance of nonpermissive GVH HLA-DPB1 mismatches for lowering the risk for grade II to IV and III to IV aGVHD. Permissive or nonpermissive HVG HLA-DPB1 mismatches may be preferred over HLA-DPB1 matches in the intermediate-risk patients to decrease the risk for disease progression.

• Authors: Betül Oran, Rima M Saliba, Yudith Carmazzi, Marcos de Lima, Gabriela Rondon, Sairah Ahmed, Amin Alousi, Borje S Andersson, Paolo Anderlini, Michelle Alvarez, Qasier Bashir, Stefan Ciurea, Marcelo Fernandez-Vina, Chitra Hosing, Partow Kebriaei, Martin Korbling, Pedro Cano, Issa Khouri, David Marin, Yago Nieto, Amanda Olson, Uday Popat, Katy Rezvani, Muzaffar Qazilbash, Elizabeth J Shpall, Richard E Champlin, Kai Cao
• Journal: Blood (Blood) Vol. 131 Issue 11 Pg. 1248-1257 (03 15 2018) ISSN: 1528-0020 [Electronic] United States
• PMID: 29386198 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 by The American Society of Hematology.

Chemical References

• HLA-DRB1 Chains

Topics

• Acute Disease
• Adult
• Aged
• Allografts
• Disease-Free Survival
• Female
• Graft vs Host Disease (metabolism, mortality, pathology, prevention & control)
• HLA-DRB1 Chains
• Hematologic Neoplasms (metabolism, mortality, pathology, therapy)
• Hematopoietic Stem Cell Transplantation
• Histocompatibility Testing
• Humans
• Lymphocyte Depletion
• Male
• Middle Aged
• Risk Factors
• Survival Rate
• T-Lymphocytes