Cytokine profiles in patients with newly diagnosed diffuse large B-cell lymphoma: IL-6 and IL-10 levels are associated with adverse clinical features and poor outcomes.

ABSTRACT

BACKGROUND: The development of diffuse large B-cell lymphoma (DLBCL), a prevalent subgroup of non-Hodgkin lymphoma (NHL), potentially involves various cytokines. We aimed to determine the correlation between deregulated serum levels of cytokines and clinical features and investigate their impact on the prognosis of patients with DLBCL. METHODS: We conducted a retrospective study of 77 patients with newly diagnosed DLBCL to explore the relationships between different cytokines, adverse clinical features, and poor outcomes. The Mann-Whitney U test was used to compare the cytokine profiles between patients with DLBCL and healthy controls. The Kaplan-Meier method was used to analyze the probability of survival, and the log-rank tests were used to evaluate the differences between survival curves. The Cox proportional hazards regression model was used to performed univariate and multivariate analyses to evaluate prognostic variables for survival analyze. RESULTS: Serum levels of interleukin-2 (IL-2), tumor necrosis factor (TNF)-α, IL-6, IL-10, and IFN-γ were significantly elevated in patients with untreated DLBCL. Serum levels of IL-6 and IL-10 were significantly higher in patients with an International Prognostic Index (IPI) of 3-5, bone marrow involvement, serum levels of LDH ≥ 250 U/L, and ß2-microglobulin (ß2-MG) levels ≥ 2.3 mg/L. Patients with B symptoms only had higher serum IL-10 levels, whereas patients with a partial response or no response to treatment had significantly elevated serum levels of IL-6 as well as IL-10. Significant positive correlations were observed between the levels of IL-6 and IL-10 with those of ß2-MG and LDH. Patients with levels of IL-6 ≥ 4.5 or IL-10 ≥ 5.0 pg/mL, as well as combined elevated IL-6 and IL-10 levels, exhibited shorter progression-free survival and overall survival. Additionally, univariate and multivariate analyses revealed that serum levels of IL-6 ≥ 4.5 pg/mL and IL-10 ≥ 5.0 pg/mL and IPI 3-5 were independent prognostic factors for relapse and survival in patients with DLBCL. CONCLUSIONS: Pre-treatment serum IL-6 and IL-10 levels in patients with newly diagnosed DLBCL might be powerful markers for determining treatment response and predicting the prognosis of DLBCL.