Elevated soluble IL-2Rα, IL-8, and MIP-1β levels are associated with inferior outcome and are independent of MIPI score in patients with mantle cell lymphoma

Mantle cell lymphoma (MCL) is a unique type of lymphoma with a prognosis intermediate between indolent and aggressive types. The purpose of this study was to study blood cytokine levels in newly diagnosed and relapsed MCL patients with respect to patterns of abnormalities and relationship to the MCL International Prognostic Index (MIPI) score. We analyzed blood levels of 30 cytokines using a multiplex ELISA in 88 patients with newly diagnosed MCL (pre-treatment levels) and 20 with relapsed MCL and compared them with controls without known lymphoma. Elevated cytokine levels were compared with clinical outcome and the MIPI score. In the 88 newly diagnosed MCL patients, we found significantly elevated levels compared with controls of IL-12, IP-10, sIL-2Rα, MIG, IL-1RA, IL-8, MIP-1α, and MIP-1β (all P<0.05). Of these elevated cytokines, sIL-2Rα, IL-8, MIG, MIP-1α, and MIP-1β were predictive of inferior event-free survival, and sIL-2Rα (HR=1.94; P=0.038), IL-8 (HR=2.17; P=0.015), and MIP-1β (HR=2.10; P=0.016) were independent of MIPI score; only sIL-2Rα (HR=2.35; P=0.041) was associated with overall survival after adjustment for MIPI. In the relapsed MCL patient group, the only significantly elevated plasma cytokines that predicted EFS were sIL-2Rα (HR=2.90; P=0.04) and IL-8 (HR=3.75; P=0.02). Elevated blood levels of sIL-2Rα and the pro-inflammatory cytokines IL-8 and MIP-1β are poor prognostic factors in MCL patients and independent of MIPI score. These factors, if validated, will provide important additions to the MIPI and guide the development of new therapies for patients with elevated levels of these cytokines.