Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 1280-1287 |
| Number of pages | 8 |
| Journal | Bone Marrow Transplantation |
| Volume | 52 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 2017 |
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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. / Fleischhauer, K; Ahn, KW; Wang, HL; Zito, L; Crivello, P; Müller, C; Verneris, M; Shaw, BE; Pidala, J; Oudshorn, M; Lee, SJ; Spellman, SR.
In: Bone Marrow Transplantation, Vol. 52, No. 9, 2017, p. 1280-1287.Research output: Contribution to journal › Article
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TY - JOUR
T1 - 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
AU - Fleischhauer, K
AU - Ahn, KW
AU - Wang, HL
AU - Zito, L
AU - Crivello, P
AU - Müller, C
AU - Verneris, M
AU - Shaw, BE
AU - Pidala, J
AU - Oudshorn, M
AU - Lee, SJ
AU - Spellman, SR
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
U2 - 10.1038/bmt.2017.96
DO - 10.1038/bmt.2017.96
M3 - Article
VL - 52
SP - 1280
EP - 1287
JO - Bone Marrow Transplantation
JF - Bone Marrow Transplantation
SN - 0268-3369
IS - 9
ER -