Faculty Collaboration Database

Directionality of non-permissive HLA-DPB1 T-cell epitope group mismatches does not improve clinical risk stratification in 8/8 matched unrelated donor hematopoietic cell transplantation. Bone Marrow Transplant 2017 Sep;52(9):1280-1287

Date

06/06/2017

Pubmed ID

28581467

Pubmed Central ID

PMC5968827

DOI

10.1038/bmt.2017.96

Scopus ID

2-s2.0-85028864903 (requires institutional sign-in at Scopus site)   14 Citations

Abstract

In 8/8 HLA-matched unrelated donor (UD) hematopoietic cell transplants (HCT), HLA-DPB1 mismatches between alleles from different T-cell epitope (TCE) groups (non-permissive mismatches) are associated with significantly higher risks of mortality compared with those between alleles from the same TCE group (permissive mismatches); however, the relevance of mismatch directionality, that is (host vs graft (uni-directional HvG), graft vs host (uni-directional GvH) or both (bi-directional) in the non-permissive setting is unknown. We show here significantly higher in vitro relative responses (RR) to bi-directional mismatches compared with uni-directional HvG or GvH mismatches in a total of 420 one-way mixed lymphocyte reactions between 10/10 matched pairs (RR 27.5 vs 7.5 vs 15.5, respectively, P<0.001). However, in 3281 8/8 matched UD HCT for leukemia or myelodysplastic syndrome, the hazards of transplant-related mortality (TRM) were similar for uni-directional HvG or GvH mismatches and bi-directional mismatches (hazard ratio (HR) 1.32, P=0.001 vs HR 1.28, P=0.005 and HR 1.34, P=0.046), compared with permissive mismatches. Similar results were observed for overall survival. No statistical differences between the uni- and the bi-directional non-permissive groups were detected in pairwise comparisons for any of the outcomes tested. We conclude that consideration of directionality does not improve risk stratification by non-permissive HLA-DPB1 TCE mismatches in UD searches.

Author List

Fleischhauer K, Ahn KW, Wang HL, Zito L, Crivello P, Müller C, Verneris M, Shaw BE, Pidala J, Oudshorn M, Lee SJ, Spellman SR

Authors

Kwang Woo Ahn PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin
Bronwen E. Shaw MBChB, PhD Center Director, Professor in the Medicine department at Medical College of Wisconsin

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

Adolescent
Adult
Aged
Child
Child, Preschool
Epitopes, T-Lymphocyte
Female
HLA-DP beta-Chains
Hematopoietic Stem Cell Transplantation
Humans
Infant
Male
Middle Aged
Transplantation Conditioning
Unrelated Donors
Young Adult