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

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 and Kai Cao

Key points

  • After HSCT with in vivo T cell depletion using ATG, HLA-DPB1 non-permissive mismatches at GvH direction increase the risk of aGvHD.

  • HLA-DPB1 matched pairs have increased risk of disease progression if intermediate risk by Disease Risk Index.

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.

  • Submitted July 28, 2017.
  • Accepted January 19, 2018.