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

Research paper by Betül B Oran, Rima M RM Saliba, Yudith Y Carmazzi, Marcos M de Lima, Gabriela G Rondon, Sairah S Ahmed, Amin A Alousi, Borje S BS Andersson, Paolo P Anderlini, Michelle M Alvarez, Qasier Q Bashir, Stefan S Ciurea, Marcelo M Fernandez-Vina, Chitra C Hosing, Partow P Kebriaei, et al.

Indexed on: 02 Feb '18Published on: 02 Feb '18Published in: Blood



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 ATG for patients with hematological malignancies. All donor-recipient pairs had high resolution typing for HLA-A, -B, -C, -DRB1, -DQB1, -DPB1 and -DRB3/4/5 and were matched at HLA-A, -B, -C and -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%) non-permissive mismatches, in graft versus host (GvH) direction and 167 (17%) non-permissive mismatches in host versus graft (HvG) direction. Compared with HLA-DPB1 permissive mismatched pairs, non-permissive GvH mismatched pairs had the highest risk of grade II-IV acute graft versus host disease (aGvHD) (HR=1.4, p=0.01) while matched pairs had the lowest risk (HR=0.5, p<0.001). Grade III-IV aGvHD was only increased with non-permissive GvH mismatched (HR=2.3, p=0.005). The risk of disease progression was lower with any HLA-DPB1 mismatches, permissive or non-permissive However the favorable prognosis of HLA-DPB1 mismatches on disease progression was observed only in peripheral blood stem cell recipients that were in the intermediate risk group by the disease risk index (HR=0.4, p=0.001) but no other risk groups. Our results suggest avoidance of non-permissive GvH HLA-DPB1 mismatches for lowering the risk of grade II-IV and III-IV aGvHD. Permissive or non-permissive HvG HLA-DPB1 mismatches may be preferred over HLA-DPB1 matched donors in the intermediate risk patients to decrease the risk of disease progression.

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