title: Serum tumor necrosis factor-α and interleukin-10 levels as markers to predict outcome of patients with chronic lymphocytic leukemia in different risk groups defined by the IGHV mutation status.
abstract: Tumor necrosis factor (TNF)-α and interleukin (IL)-10 are cytokines involved in the balance between cell-mediated and humoral immunity. We investigated whether serum TNF-α and IL-10 levels have any impact on clinical outcome of patients with chronic lymphocytic leukemia (CLL). TNF-α and IL-10 levels were determined in the serum of 160 CLL patients at the time of diagnosis. The cytokine low-risk group consisted of patients with either TNF-α and IL-10 levels below their medians or those with only one elevated parameter. Both TNF-α and IL-10 levels greater than or equal to their medians defined the cytokine high-risk group. The high-risk patients presented a shorter 3-year treatment-free survival (TFS) than low-risk subjects (15 vs. 69.6 %; p < 0.0001). The high-risk group (p = 0.0002) along with high leukocyte count (p < 0.0001) and unmutated immunoglobulin heavy-chain variable region genes (p < 0.0001) independently predict the risk of progression in patients with Rai stage 0-II. Furthermore, the high-risk group had an independent prognostic impact on shorter TFS both in patients with mutated (24.3 vs. 78.2 %; p < 0.0001) and unmutated (8.2 vs. 49 %; p = 0.004) immunoglobulin heavy-chain variable region genes (IGHV) as compared to the low-risk group. The estimated 5-year overall survival (OS) of high-risk patients was shorter than those in the low-risk group (83.3 vs. 97.1 %; p = 0.003). Multivariate analysis demonstrated the cytokine high-risk group (p = 0.02) followed by Rai stage III-IV (p = 0.048) to be independent factors predicting shorter OS. At diagnosis, TNF-α and IL-10 may predict the outcome of patients with CLL.
authors.affiliation: Institute of Hematology and Transfusion Medicine, Indiry Gandhi 14 str, 02-776, Warsaw, Poland. ewamaranda@wp.pl
authors.forename: Ewa
authors.initials: E
authors.lastname: Lech-Maranda
authors.forename: Olga
authors.initials: O
authors.lastname: Grzybowska-Izydorczyk
authors.forename: Krystyna
authors.initials: K
authors.lastname: Wyka
authors.forename: Wojciech
authors.initials: W
authors.lastname: Mlynarski
authors.forename: Maciej
authors.initials: M
authors.lastname: Borowiec
authors.forename: Karolina
authors.initials: K
authors.lastname: Antosik
authors.forename: Barbara
authors.initials: B
authors.lastname: Cebula-Obrzut
authors.forename: Hanna
authors.initials: H
authors.lastname: Makuch-Lasica
authors.forename: Grazyna
authors.initials: G
authors.lastname: Nowak
authors.forename: Gabriela
authors.initials: G
authors.lastname: Klimkiewicz-Wojciechowska
authors.forename: Ewa
authors.initials: E
authors.lastname: Wawrzyniak
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Bilinski
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Robak
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Warzocha
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D016009:Chi-Square Distribution; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D016753:Interleukin-10 / Q000097:blood*; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology* / Q000401:mortality; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D016017:Odds Ratio; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C508609:IL10 protein, human; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10