Analysis of Single Nucleotide Polymorphisms in the Gamma Block of the Major Histocompatibility Complex in Association with Clinical Outcomes of Hematopoietic Cell Transplantation: A Center for International Blood and Marrow Transplant Research Study.
Biol Blood Marrow Transplant
; 25(4): 664-672, 2019 04.
Article
en En
| MEDLINE
| ID: mdl-30537553
HLA haplotype mismatches have been associated with an elevated risk of acute graft-versus-host disease (aGVHD) in patients undergoing HLA-matched unrelated donor (URD) hematopoietic cell transplantation (HCT). The gamma block (GB) is located in the central MHC region between beta and delta blocks (encoding HLA-B and -C and HLA-DQ and -DR antigens, respectively) and contains numerous inflammatory and immune regulatory genes, including Bf, C2, and C4 genes. A single-center study showed that mismatches in SNPs c.2918+98G, c.3316C, and c.4385C in the GB block (C4 SNPs) were associated with higher risk of grade III-IV aGVHD. We investigated the association of GB SNP (GBS) mismatches with outcomes after 10/10 and 9/10 URD HCT (nâ¯=â¯714). The primary outcome was acute GVHD. Overall survival, disease-free survival, transplantation-related mortality, relapse, chronic GVHD, and engraftment were also analyzed. DNA samples were GBS genotyped by identifying 338 SNPs across 20 kb using the Illumina NGS platform. The overall 100-day incidence of aGVHD grade II-IV and II-IV were 41% and 17%, respectively. The overall incidence of matching at all GBSs tested and at the C4 SNPs were 23% and 81%, respectively. Neither being matched across all GB SNPs tested (versus mismatched) nor having a higher number of GBS mismatches was associated with transplantation outcomes. There was no association between C4 SNP mismatches and outcomes except for an unexpected significant association between having 2 C4 SNP mismatches and a higher hazard ratio (HR) for relapse (association seen in 15 patients only; HR, 3.38, 95% confidence interval, 1.75 to 6.53; Pâ¯=â¯.0003). These data do not support the hypothesis that mismatching at GB is associated with outcomes after HCT.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Prueba de Histocompatibilidad
/
Trasplante de Células Madre Hematopoyéticas
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Acondicionamiento Pretrasplante
/
Polimorfismo de Nucleótido Simple
/
Complejo Mayor de Histocompatibilidad
Tipo de estudio:
Risk_factors_studies
Límite:
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Biol Blood Marrow Transplant
Asunto de la revista:
HEMATOLOGIA
/
TRANSPLANTE
Año:
2019
Tipo del documento:
Article
Pais de publicación:
Estados Unidos