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.