Directionality of non-permissive HLA-DPB1 T-cell epitope group mismatches does not improve clinical risk stratification in 8/8 matched unrelated donor hematopoietic ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2017-09

AUTHORS

K Fleischhauer, K W Ahn, H L Wang, L Zito, P Crivello, C Müller, M Verneris, B E Shaw, J Pidala, M Oudshorn, S J Lee, S R Spellman

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. More... »

PAGES

1280

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/bmt.2017.96

DOI

http://dx.doi.org/10.1038/bmt.2017.96

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1085862188

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28581467


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