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Nonpermissive HLA-DPB1 mismatch increases mortality after myeloablative unrelated allogeneic hematopoietic cell transplantation. Blood 2014 Oct 16;124(16):2596-606 PMID: 25161269 PMCID: PMC4199961

Pubmed ID

25161269

Abstract

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.

Author List

Pidala J, Lee SJ, Ahn KW, Spellman S, Wang HL, Aljurf M, Askar M, Dehn J, Fernandez ViƱa M, Gratwohl A, Gupta V, Hanna R, Horowitz MM, Hurley CK, Inamoto Y, Kassim AA, Nishihori T, Mueller C, Oudshoorn M, Petersdorf EW, Prasad V, Robinson J, Saber W, Schultz KR, Shaw B, Storek J, Wood WA, Woolfrey AE, Anasetti C

Authors

Kwang Woo Ahn PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin
Mary M. Horowitz MD, MS Center Director, Professor in the Medicine department at Medical College of Wisconsin
Wael Saber MD, MS Associate Professor in the Medicine department at Medical College of Wisconsin
Bronwen E. Shaw MBChB, PhD Professor in the Medicine department at Medical College of Wisconsin




Scopus

2-s2.0-84908131214   87 Citations

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Child
Female
Graft vs Host Disease
HLA-DP beta-Chains
Hematopoietic Stem Cell Transplantation
Histocompatibility
Histocompatibility Testing
Humans
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Acute
Male
Middle Aged
Myelodysplastic Syndromes
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Retrospective Studies
Transplantation, Homologous
Unrelated Donors
Young Adult
jenkins-FCD Prod-299 9ef562391eceb2b8f95265c767fbba1ce5a52fd6