Increased serum levels of interleukin-15 correlate with negative prognostic factors in extranodal NK/T cell lymphoma

Interleukin-15 (IL-15) is a proinflammatory cytokine involved in the proliferation, survival, and activation of multiple lymphocyte lineages. However, the prognostic significance of IL-15 for extranodal NK/T cell lymphoma (ENKTL) has not been well established. We retrospectively analyzed 112 patients with newly diagnosed ENKTL. Baseline serum IL-15 levels were determined using sandwich enzyme-linked immunosorbent assays. Patients with high IL-15 (>3.94 mg/L) at diagnosis tended to have more adverse clinical features. Patients with low IL-15 (<= 3.94 mg/L) at diagnosis had better progression-free survival (PFS; P < 0.001) and overall survival (OS; P < 0.001) and achieved higher complete remission rates (P = 0.001). Multivariate analysis revealed independent prognostic factors for PFS. Similarly, high IL-15 levels (P = 0.009), no CR after chemotherapy (P = 0.001), Stage III/IV (P = 0.048), and elevated serum EBV-DNA (P = 0.038) were independently predictive of shorter OS. Using the International Prognostic Index or Korean Prognostic Index for nasal NK/T cell lymphoma, the majority of patients were in the low-risk category (with no or one adverse factor). Serum IL-15 was helpful to differentiate the low-risk patients with different survival outcomes (P < 0.001). Our data suggest that serum IL-15 at diagnosis is a novel, powerful predictor of prognosis for ENKTL, which suggests a role for IL-15 in the pathogenesis of this disease and offers new insight into potential therapeutic strategies.