title: Elevated circulating levels of TNFalpha and its p55 soluble receptor are associated with an adverse prognosis in lymphoma patients.
abstract: In 88 newly diagnosed lymphoma patients, tumour necrosis factor alpha (TNFalpha) 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 TNFalpha 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 TNFalpha level > or = 20 pg/ml was significantly associated with elevated LDH level (P<0.0001), serum beta2-microglobulin level > or = 3 mg/l (P<0.0001), haemoglobin < or = 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 TNFalpha was also associated with B symptoms (P<0.005), poor performance status (P<0.05), and serum albumin < or = 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 > or = 3.5 ng/ml was significantly associated with poor performance status (P<0.0001), B symptoms (P<0.0001), beta2-microglobulin levels > or = 3 mg/l (P<0.0001), serum albumin < or = 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 < or = 12 g/dl (P<0.005), and bulky tumour (P<0.001). In the whole group of 88 patients, both high TNFalpha 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<0.001 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 TNF gamma and p55-R-TNF levels have high correlation with other adverse prognostic factors in lymphoma patients and may predict a poor outcome.
authors.affiliation: Service d'Hématologie and Groupe de Recherche sur les Hémopathies Lymphoïdes Malignes, Lyon, France.
authors.forename: G
authors.initials: G
authors.lastname: Salles
authors.forename: J
authors.initials: J
authors.lastname: Bienvenu
authors.forename: Y
authors.initials: Y
authors.lastname: Bastion
authors.forename: Y
authors.initials: Y
authors.lastname: Barbier
authors.forename: C
authors.initials: C
authors.lastname: Doche
authors.forename: K
authors.initials: K
authors.lastname: Warzocha
authors.forename: M C
authors.initials: MC
authors.lastname: Gutowski
authors.forename: C
authors.initials: C
authors.lastname: Rieux
authors.forename: B
authors.initials: B
authors.lastname: Coiffier
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism*; D006801:Humans; D008224:Lymphoma, Follicular / Q000097:blood*; D008228:Lymphoma, Non-Hodgkin / Q000097:blood*; D011379:Prognosis; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha