Associations of minor histocompatibility antigens with outcomes following allogeneic hematopoietic cell transplantation.
Journal
American journal of hematology
ISSN: 1096-8652
Titre abrégé: Am J Hematol
Pays: United States
ID NLM: 7610369
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
revised:
09
03
2023
received:
14
01
2023
accepted:
23
03
2023
medline:
15
5
2023
pubmed:
14
4
2023
entrez:
13
4
2023
Statut:
ppublish
Résumé
The role of minor histocompatibility antigens (mHAs) in mediating graft versus leukemia and graft versus host disease (GvHD) following allogeneic hematopoietic cell transplantation (alloHCT) is recognized but not well-characterized. By implementing improved methods for mHA prediction in two large patient cohorts, this study aimed to comprehensively explore the role of mHAs in alloHCT by analyzing whether (1) the number of predicted mHAs, or (2) individual mHAs are associated with clinical outcomes. The study population consisted of 2249 donor-recipient pairs treated for acute myeloid leukemia and myelodysplastic syndrome with alloHCT. A Cox proportional hazard model showed that patients with a class I mHA count greater than the population median had an increased hazard of GvHD mortality (hazard ratio [HR] = 1.39, 95% confidence interval [CI] = 1.01, 1.77, p = .046). Competing risk analyses identified the class I mHAs DLRCKYISL (GSTP), WEHGPTSLL (CRISPLD2), and STSPTTNVL (SERPINF2) were associated with increased GVHD mortality (HR = 2.84, 95% CI = 1.52, 5.31, p = .01), decreased leukemia-free survival (LFS) (HR = 1.94, 95% CI = 1.27, 2.95, p = .044), and increased disease-related mortality (DRM) (HR = 2.32, 95% CI = 1.5, 3.6, p = .008), respectively. One class II mHA YQEIAAIPSAGRERQ (TACC2) was associated with increased risk of treatment-related mortality (TRM) (HR = 3.05, 95% CI = 1.75, 5.31, p = .02). WEHGPTSLL and STSPTTNVL were both present within HLA haplotype B*40:01-C*03:04 and showed a positive dose-response relationship with increased all-cause mortality and DRM and decreased LFS, indicating these two mHAs contribute to the risk of mortality in an additive manner. Our study reports the first large-scale investigation of the associations of predicted mHA peptides with clinical outcomes following alloHCT.
Identifiants
pubmed: 37052167
doi: 10.1002/ajh.26925
pmc: PMC10368187
mid: NIHMS1898570
doi:
Substances chimiques
Minor Histocompatibility Antigens
0
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
940-950Subventions
Organisme : NCI NIH HHS
ID : P30 CA016056
Pays : United States
Organisme : HRSA HHS
ID : HHSH250201700007C
Pays : United States
Organisme : NHLBI NIH HHS
ID : U24 HL157560
Pays : United States
Organisme : HRSA HHS
ID : HHSH250201700006C
Pays : United States
Organisme : HRSA HHS
ID : HHSH250201700005C
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL102278
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA247676
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA076518
Pays : United States
Organisme : NHLBI NIH HHS
ID : U24 HL138660
Pays : United States
Informations de copyright
© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.
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