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ELEVATED CIRCULATING LEVELS OF TNFα AND ITS p55 SOLUBLE RECEPTOR ARE ASSOCIATED WITH AN ADVERSE PROGNOSIS IN LYMPHOMA PATIENTS
Author(s) -
SALLES Gilles,
BIENVENU Jacques,
BASTION Yves,
BARBIER Yves,
DOCHE Christophe,
WARZOCHA Krzysztof,
GUTOWSKI MarieClaude,
RIEUX Claire,
COIFFIER Bertrand
Publication year - 1996
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1996.5181059.x
Subject(s) - immunoradiometric assay , medicine , beta 2 microglobulin , lymphoma , gastroenterology , tumor necrosis factor alpha , albumin , endocrinology , radioimmunoassay
In 88 newly diagnosed lymphoma patients, tumour necrosis factor alpha (TNFα) and soluble TNF type I receptor (p55‐R‐TNF) were prospectively determined in plasma by immunoradiometric assay (IRMA) and ELISA methods respectively. These 88 patients included 19 with centrocyto‐centroblastic lymphoma, 13 patients with other low‐grade lymphoma, and 56 with high‐grade lymphoma. Median TNFα 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 TNFα level ≥20 pg/ml was significantly associated with elevated LDH level ( P < 0.0001), serum β2‐microglobulin level ≥ 3 mg/l ( P < 0.0001), haemoglobin ≤ 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 TNFα was also associated with B symptoms ( P < 0.005), poor performance status ( P < 0.05), and serum albumin ≤ 35 g/l ( P < 0.05). Levels of p55‐R‐TNF 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 ≥ 3.5 ng/ml was significantly associated with poor performance status ( P < 0.0001), B symptoms ( P < 0.0001), β2‐microglobulin levels ≥ 3 mg/l ( P < 0.0001), serum albumin ≤ 35 g/l ( P = 0.0001), C‐reactive protein > 6 mg/l ( P = 0.0003), elevated (> 20 pg/ml) IL‐6 level ( P < 0.005), haemoglobin ≤ 12 g/dl ( P < 0.005), and bulky tumour ( P < 0.001). In the whole group of 88 patients, both high TNFα and p55‐R‐TNF levels strongly predicted short progression‐free survival ( P < 0.005 for both variables) and overall survival ( P < 0.001 and P < 0.0001 respectively). In multivariate analyses the elevation of p55‐R‐TNF retained a higher significance over the other variables and therefore improved the predictive value of the International Prognostic Index. This study suggests that elevated TNFα and p55‐R‐TNF levels have a high correlation with other adverse prognostic factors in lymphoma patients and may predict a poor outcome.