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

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

Research output: Contribution to journalArticle

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. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
Original languageEnglish
Pages (from-to)1280-1287
Number of pages8
JournalBone Marrow Transplantation
Volume52
Issue number9
DOIs
Publication statusPublished - 2017

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    Fleischhauer, K., Ahn, KW., Wang, HL., Zito, L., Crivello, P., Müller, C., Verneris, M., Shaw, BE., Pidala, J., Oudshorn, M., Lee, SJ., & Spellman, SR. (2017). 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 Transplantation, 52(9), 1280-1287. https://doi.org/10.1038/bmt.2017.96