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Permissible HLA mismatches in 9/10 unrelated donor pediatric stem cell transplants using HLA-EMMA, an EBMT IEWP Study.
- Source :
-
Blood advances [Blood Adv] 2024 Jul 10. Date of Electronic Publication: 2024 Jul 10. - Publication Year :
- 2024
- Publisher :
- Ahead of Print
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Abstract
- HSCT with mismatched unrelated donors (MMUD) is associated with inferior outcome compared to matched unrelated donors. We aimed to identify permissible mismatches using HLA-EMMA, which determines permissibility by analyzing amino-acid (AA) sequences, in a single center cohort of 70 pediatric 9/10 MMUD HSCTs and 157 10/10 MUDs for comparison. AA matching was evaluated for the whole HLA protein, the α-helices, and the β-sheets, in both Host versus Graft (HvG) and Graft vs Host (GvH) direction. Superior EFS was found in 13 patients permissibly mismatched in the HvG direction (totalHvG, 92% vs 58% at 1 year, p=0.009), and in 21 patients matched for AA on the α-helices (αHvG, 90% vs 53%, p=0.002), similar to EFS with 10/10 MUDs (90% vs 80%, p=0.60). EFS was not related to β-sheet AA matching, nor to matching in the GvH direction. OS trended similarly as EFS for AA mismatches (totalHvG, 92% vs 74%, p=0.075 and αHvG90% vs 71%, p=0.072). These findings were reproduced in an EBMT inborn errors cohort of 271 pediatric 9/10 MMUD HSCTs and 929 10/10 MUD HSCTs, showing a significant effect of αHvG matching on both OS and EFS and similar OS and EFS between αHvG matched MMUDs and 10/10 MUDs. In summary, HvG-AA matching on the α-helices identifies 9/10 MMUD with permissible mismatches correlated with a favorable transplant outcome similar to matched donors.<br /> (Copyright © 2024 American Society of Hematology.)
Details
- Language :
- English
- ISSN :
- 2473-9537
- Database :
- MEDLINE
- Journal :
- Blood advances
- Publication Type :
- Academic Journal
- Accession number :
- 38985189
- Full Text :
- https://doi.org/10.1182/bloodadvances.2024012945