Document Detail


Tumor necrosis factor polymorphism affects transplantation outcome in patients with myelodysplastic syndrome but not in those with chronic myelogenous leukemia, independent of the presence of HLA-DR15.
MedLine Citation:
PMID:  20541027     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Both the presence of HLA-DR15 and tumor necrosis factor (TNF)-α levels have been reported to affect outcome after hematopoietic cell transplantation (HCT). Patients with a myelodysplastic syndrome (MDS) show a high prevalence of HLA-DR15 and express high levels of TNF-α in the bone marrow. The present analysis involving 7950 patients showed an HLA-DR15 frequency of 31% in patients with MDS, compared with only 23% in patients with chronic myelogenous leukemia (CML). HLA-DR15 was more prevalent in Caucasian patients than in non-Caucasian patients (P = .01). The numbers of patients in the non-Caucasian subgroups were too small to allow further analysis. Among Caucasian patients with MDS and CML, the presence of HLA-DR15 did not significantly affect the occurrence of graft-versus-host disease, relapse, nonrelapse mortality (NRM), or survival. However, there was a significant correlation between DR15 and TNF polymorphisms at position -308 among patients with MDS, and the TNF-308 AG genotype conferred an increased risk of NRM compared with the GG genotype (hazard ratio [HR], 1.49; P = .02), even after adjusting for DR15. Conversely, the TNF-863 AA genotype was correlated with decreased overall mortality and NRM compared with the CC genotype (HR, 0.36, P = .04 vs HR, 0.13, P = .04), even after adjusting for DR15. There was no significant association between TNF-308 or -863 polymorphisms and transplantation outcome in CML patients. These results suggest that TNF polymorphisms, but not DR15, affect transplantation outcome in a disease-dependent manner.
Authors:
Laura F Newell; Ted Gooley; John A Hansen; Derek L Stirewalt; Effie W Petersdorf; H Joachim Deeg
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-06-09
Journal Detail:
Title:  Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation     Volume:  16     ISSN:  1523-6536     ISO Abbreviation:  Biol. Blood Marrow Transplant.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-08     Completed Date:  2011-04-04     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  9600628     Medline TA:  Biol Blood Marrow Transplant     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1700-6     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
Affiliation:
Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N., Seattle, WA 98109, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Cohort Studies
Female
HLA-DR Antigens / immunology*
HLA-DR Serological Subtypes
Hematopoietic Stem Cell Transplantation / methods*
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*,  immunology,  surgery*
Male
Middle Aged
Myelodysplastic Syndromes / genetics*,  immunology,  surgery*
Polymorphism, Genetic
Retrospective Studies
Transplantation, Homologous
Treatment Outcome
Tumor Necrosis Factors / genetics*,  immunology
Grant Support
ID/Acronym/Agency:
AI33484/AI/NIAID NIH HHS; CA15704/CA/NCI NIH HHS; CA18029/CA/NCI NIH HHS; HL036444/HL/NHLBI NIH HHS; P01 AI033484-15/AI/NIAID NIH HHS; P01 CA018029/CA/NCI NIH HHS; P01 CA018029-36/CA/NCI NIH HHS; P01 HL036444-30/HL/NHLBI NIH HHS; P30 CA015704-37/CA/NCI NIH HHS; R01 CA100019-09/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/HLA-DR Antigens; 0/HLA-DR Serological Subtypes; 0/HLA-DR15 antigen; 0/Tumor Necrosis Factors
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