ELEVATED CIRCULATING LEVELS OF TNF-ALPHA AND ITS P55 SOLUBLE RECEPTORARE ASSOCIATED WITH AN ADVERSE PROGNOSIS IN LYMPHOMA PATIENTS

In 88 newly diagnosed lymphoma patients, tumour necrosis factor alpha (TNF alpha) and soluble TNF type I receptor (p55-R-TNF) were prospecti vely determined in plasma by immunoradiometric assay (IRMA) and ELISA methods respectively. These 88 patients included 19 with centrocyto-ce ntroblastic lymphoma, 13 patients with other low-grade lymphoma, and 5 6 with high-grade lymphoma, 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 20 healthy control subjects. Presence of TNF alpha level greater than or equal to 20 pg/ml was significantly associated with elevated LDH l evel (P < 0.0001), serum beta 2-microglobulin level greater than or eq ual to 3 mg/l (P < 0.0001), haemoglobin less than or equal to 12 g/dl (P = 0.0001), Ann Arbor stage III or IV disease (P < 0.005), and with bulky tumour (P = 0.01). High level of TNF alpha was also associated w ith B symptoms (P < 0.005), poor performance status (P < 0.05), and se rum albumin less than or equal to 35 g/l (P < 0.05), Levels of p55-R-T NF 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-R-TNF greater than or equal to 3.5 ng/ml was significantly associated with poor performance status (P < 0.0001), B symptoms (P < 0.0001), P2-microglobulin levels greater than or equal to 3 mg/l (P < 0.0001), serum albumin less than or equal to 35 g/l (P = 0.0001), C-reactive protein > 6 mg/l (P = 0.0003), elevate d (> 20 pg/ml) IL-6 level (P < 0.005), haemoglobin less than or equal to 12 g/dl (P < 0.005), and bulky tumour (P < 0.001). In the whole gro up of 88 patients, both high TNF alpha and p55-R-TNF levels strongly p redicted short progression-free survival (P < 0.005 for both variables ) and overall survival (P < 0.001 and P < 0.0001 respectively). In mul tivariate analyses the elevation of p55-R-TNF retained a higher signif icance over the other variables and therefore improved the predictive value of the International Prognostic Index. This study suggests that elevated TNF alpha and p55-R-TNF levels have a high correlation with o ther adverse prognostic factors in lymphoma patients and may predict a poor outcome.