Prognostic significance of TNF alpha and its p55 soluble receptor in malignant lymphomas

In 93 newly diagnosed lymphoma patients, tumor necrosis factor alpha (TNF alpha) and its p55 soluble receptor (p55-sR), were prospectively determined in plasma by IRMA and ELISA methods respectively. These 93 patients included 31 patients with low grade lymphoma, 55 with intermediate or high grade lymphoma and 7 with Hodgkin's disease. Median TNF alpha plasma values were 20 pg/mL (range 5-380 pg/mL) in patients versus 7 pg/mL (range 4-9 pg/mL) in healthy control subjects. Presence of TNF alpha level equal or greater than 20 pg/mL was significantly associated with elevated LDH level, serum beta 2-microglobulin level > or = 3 mg/L, hemoglobin < or = 12 g/dL, Ann Arbor stage III or IV disease, and with bulky tumor. High level of TNF alpha was also associated, although less strongly, with B symptoms, poor performance status, and serum albumin < or = 35 g/L, yet it was not associated with change in acute phase protein levels. Levels of p55-sR were also markedly elevated in these lymphoma patients (median of 3.5 ng/mL, range 0.8-18.8 ng/mL) versus 1.45 ng/mL in control subjects (range 1.1-2.3 ng/mL). Level of p55-sR equal or greater than 3.5 ng/mL was significantly associated with poor performance status, B symptoms, beta 2-microglobulin levels > or = 3 mg/L, serum albumin < or = 35 g/L, C-reactive protein > 6 mg/L, hemoglobin < or = 12 g/dL, and bulky tumor. In the whole group of 93 patients, both high TNF alpha and p55-sR levels strongly predicted short freedom from progression and overall survival. This study suggests that elevated TNF alpha and p55-sR plasma levels have a high correlation with other adverse prognostic factors in lymphoma patients and predict their poor outcome.