JOURNAL ARTICLE

Nonpermissive HLA-DPB1 mismatch increases mortality after myeloablative unrelated allogeneic hematopoietic cell transplantation

Joseph Pidala, Stephanie J Lee, Kwang Woo Ahn, Stephen Spellman, Hai-Lin Wang, Mahmoud Aljurf, Medhat Askar, Jason Dehn, Marcelo Fernandez Viña, Alois Gratwohl, Vikas Gupta, Rabi Hanna, Mary M Horowitz, Carolyn K Hurley, Yoshihiro Inamoto, Adetola A Kassim, Taiga Nishihori, Carlheinz Mueller, Machteld Oudshoorn, Effie W Petersdorf, Vinod Prasad, James Robinson, Wael Saber, Kirk R Schultz, Bronwen Shaw, Jan Storek, William A Wood, Ann E Woolfrey, Claudio Anasetti
Blood 2014 October 16, 124 (16): 2596-606
25161269
We examined current outcomes of unrelated donor allogeneic hematopoietic cell transplantation (HCT) to determine the clinical implications of donor-recipient HLA matching. Adult and pediatric patients who had first undergone myeloablative-unrelated bone marrow or peripheral blood HCT for acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome between 1999 and 2011 were included. All had high-resolution typing for HLA-A, -B, -C, and -DRB1. Of the total (n = 8003), cases were 8/8 (n = 5449), 7/8 (n = 2071), or 6/8 (n = 483) matched. HLA mismatch (6-7/8) conferred significantly increased risk for grades II to IV and III to IV acute graft vs host disease (GVHD), chronic GVHD, transplant-related mortality (TRM), and overall mortality compared with HLA-matched cases (8/8). Type (allele/antigen) and locus (HLA-A, -B, -C, and -DRB1) of mismatch were not associated with overall mortality. Among 8/8 matched cases, HLA-DPB1 and -DQB1 mismatch resulted in increased acute GVHD, and HLA-DPB1 mismatch had decreased relapse. Nonpermissive HLA-DPB1 allele mismatch was associated with higher TRM compared with permissive HLA-DPB1 mismatch or HLA-DPB1 match and increased overall mortality compared with permissive HLA-DPB1 mismatch in 8/8 (and 10/10) matched cases. Full matching at HLA-A, -B, -C, and -DRB1 is required for optimal unrelated donor HCT survival, and avoidance of nonpermissive HLA-DPB1 mismatches in otherwise HLA-matched pairs is indicated.

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