title: Plasma TNF-alpha and IL-10 level-based prognostic model predicts outcome of patients with diffuse large B-Cell lymphoma in different risk groups defined by the International Prognostic Index.
abstract: Tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 are key cytokines involved in lymphoma development. Their pretreatment plasma levels were reported to influence the clinical course of non-Hodgkin's lymphoma. In this study the impact of combined elevation of TNF-alpha and IL-10 on disease features and outcome of patients with diffuse large B-cell lymphoma (DLBCL) were investigated. Plasma TNF-alpha and IL-10 levels were determined at the time of diagnosis in a group of 106 DLBCL patients uniformly treated with anthracycline-based regimens. Three risk groups depending on the pretreatment levels of the cytokines were identified: low-, intermediate-, and high-risk groups. In univariate analysis, the cytokine intermediate- and high-risk groups were associated with lower probability of achieving a complete remission (odds ratio [OR] = 0.2, 95% confidence interval [CI] 0.06-0.6, p = 0.006 and OR = 0.05, 95% CI 0.01-0.2, p < 0.0001, respectively) and shorter progression-free survival (PFS) (OR = 4.4, 95% CI 1.9-10.2, p < 0.001 and OR = 9.7, 95% CI 4.1-23.0, p < 0.0001, respectively) and overall survival (OS) (OR = 4.2, 95% CI 1.7-10.1, p = 0.002 and OR = 11.2, 95% CI 4.4-28.4, p < 0.0001, respectively) in comparison with the cytokine low-risk group. In multivariate analysis, the cytokine intermediate- and high-risk groups also correlated with shorter PFS (relative risk [RR] = 4.5, 95% CI 1.9-10.9, p = 0.001 and RR = 5.8, 95% CI 2.2-15.3, p < 0.0001, respectively) and OS (RR = 4.6, 95% CI 1.8-12.0, p = 0.001 and RR = 7.5, 95% CI 2.7-20.9, p < 0.0001, respectively) regardless of the International Prognostic Index (IPI) scoring system. The TNF-alpha and IL-10 level-based index may work as an additional model to the IPI for predicting the survival of DLBCL patients. This model may help to identify patients in a given IPI risk group for whom more accurate and risk-adapted treatment could be advised.
authors.affiliation: Equipe Pathologie des Cellules Lymphoïdes, UMR CNRS 5239, Université Claude Bernard, Lyon, France. ewamaranda@wp.pl
authors.forename: Ewa
authors.initials: E
authors.lastname: Lech-Maranda
authors.forename: Jacques
authors.initials: J
authors.lastname: Bienvenu
authors.forename: Florence
authors.initials: F
authors.lastname: Broussais-Guillaumot
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Warzocha
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Michallet
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Robak
authors.forename: Bertrand
authors.initials: B
authors.lastname: Coiffier
authors.forename: Gilles
authors.initials: G
authors.lastname: Salles
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000097:blood*; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011241:Prednisone / Q000008:administration & dosage; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D015854:Up-Regulation; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D015415:Biomarkers; C508609:IL10 protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone