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    
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.
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.
Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N., Seattle, WA 98109, USA.
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MeSH Terms
Cohort Studies
HLA-DR Antigens / immunology*
HLA-DR Serological Subtypes
Hematopoietic Stem Cell Transplantation / methods*
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*,  immunology,  surgery*
Middle Aged
Myelodysplastic Syndromes / genetics*,  immunology,  surgery*
Polymorphism, Genetic
Retrospective Studies
Transplantation, Homologous
Treatment Outcome
Tumor Necrosis Factors / genetics*,  immunology
Grant Support
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
Reg. No./Substance:
0/HLA-DR Antigens; 0/HLA-DR Serological Subtypes; 0/HLA-DR15 antigen; 0/Tumor Necrosis Factors

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