Prognostic value of serum interleukin-6 in diffuse large-cell lymphoma

Background: Interleukin-6 has important lymphoid bioregulatory effects, and serum levels of interleukin-6 are often elevated in patients with lymphoma. Objective: To determine the relation between serum levels of interleukin-6 before treatment and outcome in patients with diffuse large-cell lymphoma. Design: Retrospective cohort analysis with multivariate analysis. Setting: Tertiary referral center. Participants: 118 untreated patients with diffuse large-cell lymphoma who were enrolled in frontline chemotherapy protocols and 45 healthy controls. Measurements: Serum levels of interleukin-6 were measured by using a sensitive enzyme-linked immunosorbent assay. Levels below the upper limit of the range for controls were considered normal. Outcomes were complete response, failure-free survival, and overall survival. Results: Serum levels of interleukin-6 were higher in patients with lymphoma (median, 4.6 pg/mL [range, undetectable to 224 pg/mL]) than in controls (median, undetectable [range, undetectable to 4.3 pg/mL]) (P = 0.009). The complete response rate was 95% for persons with normal interleukin-6 levels and 66% for persons with high interleukin-6 levels (P = 0.001). Patients with high interleukin-6 levels had inferior failure-free and overall survival rates (P < 0.001 for both comparisons). The actuarial 4-year failure-free and overall survival rates were 72% and 85%, respectively, for persons with normal interleukin-6 levels and 37% and 46%, respectively, for persons with high interleukin-6 levels. In multivariate analysis, interleukin-6 was selected as the most significant predictor of complete response and failure-free survival. Failure-free and overall survival of patients stratified according to International Prognostic Index score could be further stratified by interleukin-6 level (P less than or equal to 0.03 for all comparisons). Conclusion: In patients with diffuse large-cell lymphoma, serum interleukin-6 levels are an independent prognostic factor for complete response and failure-free survival.