title: 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.
abstract: 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.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N., Seattle, WA 98109, USA.
authors.forename: Laura F
authors.initials: LF
authors.lastname: Newell
authors.forename: Ted
authors.initials: T
authors.lastname: Gooley
authors.forename: John A
authors.initials: JA
authors.lastname: Hansen
authors.forename: Derek L
authors.initials: DL
authors.lastname: Stirewalt
authors.forename: Effie W
authors.initials: EW
authors.lastname: Petersdorf
authors.forename: H Joachim
authors.initials: HJ
authors.lastname: Deeg
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology*; D059810:HLA-DR Serological Subtypes; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000276:immunology / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000276:immunology / Q000601:surgery*; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D048069:Tumor Necrosis Factors / Q000235:genetics* / Q000276:immunology
chemical_list: D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C106559:HLA-DR15 antigen; D048069:Tumor Necrosis Factors