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

• Published in: Archivum Immunologiae et Therapiae Experimentalis Vol. 60; no. 6; pp. 477 - 486
• Main Authors: Lech-Maranda, Ewa, Grzybowska-Izydorczyk, Olga, Wyka, Krystyna, Mlynarski, Wojciech, Borowiec, Maciej, Antosik, Karolina, Cebula-Obrzut, Barbara, Makuch-Lasica, Hanna, Nowak, Grazyna, Klimkiewicz-Wojciechowska, Gabriela, Wawrzyniak, Ewa, Bilinski, Przemyslaw, Robak, Tadeusz, Warzocha, Krzysztof
• Format: Journal Article
• Language: English
• Published: Basel SP Birkhäuser Verlag Basel 01.12.2012
• Subjects: Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers, Tumor - blood; Biomedical and Life Sciences; Biomedicine; Chi-Square Distribution; Disease-Free Survival; DNA Mutational Analysis; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Variable Region - genetics; Immunology; Interleukin-10 - blood; Kaplan-Meier Estimate; Leukemia, Lymphocytic, Chronic, B-Cell - blood; Leukemia, Lymphocytic, Chronic, B-Cell - diagnosis; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Leukemia, Lymphocytic, Chronic, B-Cell - immunology; Leukemia, Lymphocytic, Chronic, B-Cell - mortality; Logistic Models; Male; Middle Aged; Multivariate Analysis; Mutation; Odds Ratio; Original Article; Pharmacology/Toxicology; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha - blood; Up-Regulation; Chronic lymphocytic leukemia; Tumor necrosis factor-α; Immunoglobulin heavy-chain variable region genes; Interleukin-10; Outcome
• ISSN: 0004-069X; 1661-4917
• DOI: 10.1007/s00005-012-0197-7

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.