Increased serum level of interleukin-6 correlates with negative prognostic factors in extranodal NK/T-cell lymphoma

BACKGROUND: Extranodal natural killer/T-cell lymphoma (ENKTL) is a rare subtype of non-Hodgkin lymphoma (NHL), characterized as mature T- and natural killer (NK)-cell lymphoma, which is more common in East Asia and Latin America than in other parts of the world. The overproduction of proinflammatory cytokines such as interleukin-6 (IL-6) plays an essential role in the development of lymphoma. METHODS: We measured serum IL-6 and IL-6 related cytokines of 65 newly diagnosed ENKTL patients to assess biomarkers for prognosis of ENKTL. RESULTS: Patients with high IL-6 (>15.920 mg/L) at diagnosis had more adverse clinical features. Patients with low IL-6 (≤15.920 mg/L) at diagnosis had better progression-free survival (PFS; P=0.002), overall survival (OS; P<0.001), and higher complete remission rates (P=0.001). IL-6 correlated with lactate dehydrogenase (LDH), ferritin, C-reactive protein (CRP), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α). Multivariate analysis revealed Ann Arbor stage [P=0.001, risk ratio (RR) =6.011 (2.102–17.191)] and IL-6 [P=0.012, RR =2.367 (1.206–4.643)] to be independent prognostic factors for PFS. Multifactor analysis of OS revealed Ann Arbor stage [P=0.015, RR =3.600 (1.278–10.141)], IL-6 [(P=0.001), RR =3.565 (1.720–7.390)], and chemotherapy that not containing L-asparaginase [(P=0.009, RR =2.717 (1.252–5.780)] to be independent prognostic factors for shorter OS. CONCLUSIONS: These results suggest serum IL-6 at diagnosis is predictive of prognosis for ENKTL, and IL-6 increase is activity during the pathogenesis of ENKTL and offers new insight into potential therapeutic strategies.