UNIGE document Scientific Article
previous document  unige:25366  next document
add to browser collection
Title

Impact of HLA-DPB1 haplotypes on outcome of 10/10 matched unrelated hematopoietic stem cell donor transplants depends on MHC-linked microsatellite polymorphisms

Authors
Bettens, Florence
Schanz, Urs
Heim, Dominik
Güngör, Tayfun
Stussi, Georg
Nicoloso, Grazia
show hidden authors show all authors [1 - 11]
Published in Biology of Blood and Marrow Transplantation. 2011, vol. 18, no. 4, p. 608-16
Abstract Hematopoietic stem cell transplantation (HSCT) with HLA-A, -B, -C, -DRB1, -DQB1 allele matched (10 of 10) unrelated donors is still associated with a significant rate of posttransplantation complications. In order to disclose additional immunogenetic factors, we analyzed the impact of HLA-DPB1 disparities and major histocompatibility complex (MHC)-resident microsatellite polymorphisms in 246 HLA 10 of 10 matched HSCT patients. First we showed that patients with more frequent/conserved HLA haplotypes had a higher 5-year survival (55% ± 18% versus 39% ± 18%, P = .021). In addition, DPB1 incompatibilities and 3 microsatellite alleles were associated with outcome. In a Cox regression model adjusting for European Blood and Marrow Transplant (EBMT) risk score, T cell depletion, and year of treatment, HSCT with a tumor necrosis factor d (TNFd) 4/d5-positive donor was associated with increased mortality (hazard ratio [HR] = 2.03; confidence interval [CI] 1.25-3.31; P = .004), whereas the D6S510-184 allele was protective (HR = 0.44; CI 0.22-0.87; P = .018). The 2 MHC-linked genetic donor factors, DPB1 mismatch (MM), and TNFd4/d5-positivity, acted in synergy with the EBMT risk score with an always lower survival (HR = 2.97; CI 1.27-6.92; P = .012). These data show that multiple MHC-linked genetic donor factors impact on outcome after unrelated donor HSCT. Their additive and potentially divergent effects could explain previous discrepant results, particularly with respect to the role of HLA-DPB1 disparities. We conclude that HLA-DPB1 typing combined with a simple TNFd microsatellite genotyping assay may significantly help in pretransplantation risk assessment for graft-versus-host disease and mortality, particularly for patients with several potential 10 of 10 matched donors.
Keywords HSCTUnrelated donorHLA haplotype matchingHLA-DPMicrosatelliteTNFd locus
Identifiers
PMID: 21963878
Full text
Article (Published version) (310 Kb) - document accessible for UNIGE members only Limited access to UNIGE
Structures
Research group Compatibilité tissulaire et transplantation clinique (562)
Citation
(ISO format)
BETTENS, Florence et al. Impact of HLA-DPB1 haplotypes on outcome of 10/10 matched unrelated hematopoietic stem cell donor transplants depends on MHC-linked microsatellite polymorphisms. In: Biology of Blood and Marrow Transplantation, 2011, vol. 18, n° 4, p. 608-16. https://archive-ouverte.unige.ch/unige:25366

238 hits

0 download

Update

Deposited on : 2013-01-10

Export document
Format :
Citation style :