Salles G, Bienvenu J, Bastion Y, Barbier Y, Doche C, Warzocha K, Gutowski M C, Rieux C, Coiffier B
Service d'Hématologie and Groupe de Recherche sur les Hémopathies Lymphoïdes Malignes, Lyon, France.
Br J Haematol. 1996 May;93(2):352-9. doi: 10.1046/j.1365-2141.1996.5181059.x.
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.
在88例新诊断的淋巴瘤患者中，分别采用免疫放射分析（IRMA）法和酶联免疫吸附测定（ELISA）法前瞻性地测定血浆中的肿瘤坏死因子α（TNFα）和可溶性I型肿瘤坏死因子受体（p55-R-TNF）。这88例患者包括19例中心细胞-中心母细胞性淋巴瘤患者、13例其他低度淋巴瘤患者和56例高度淋巴瘤患者。患者血浆TNFα的中位数为20 pg/ml（范围5 - 380 pg/ml），而20名健康对照者为7 pg/ml（范围4 - 9 pg/ml）。TNFα水平≥20 pg/ml与乳酸脱氢酶水平升高（P<0.0001）、血清β2-微球蛋白水平≥3 mg/l（P<0.0001）、血红蛋白≤12 g/dl（P = 0.0001）、Ann Arbor分期III或IV期疾病（P<0.005）以及巨大肿瘤（P = 0.01）显著相关。高水平的TNFα还与B症状（P<0.005）、较差的体能状态（P<0.05）和血清白蛋白≤35 g/l（P<0.05）相关。这些淋巴瘤患者的p55-R-TNF水平也明显升高（中位数为3.5 ng/ml，范围0.8 - 18.8 ng/ml），而对照者为1.45 ng/ml（范围1.1 - 2.3 ng/ml）。p55-R-TNF水平≥3.5 ng/ml与较差的体能状态（P<0.0001）、B症状（P<0.0001）、β2-微球蛋白水平≥3 mg/l（P<0.0001）、血清白蛋白≤35 g/l（P = 0.0001）、C反应蛋白>6 mg/l（P = 0.0003）、白细胞介素-6水平升高（>20 pg/ml，P<0.005）、血红蛋白≤12 g/dl（P<0.005）以及巨大肿瘤（P<0.001）相关。在全部88例患者中，TNFα和p55-R-TNF水平升高均强烈预示无进展生存期短（两个变量的P均<0.005）和总生存期短（分别为P<0.001和P<0.001）。在多变量分析中，p55-R-TNF升高相对于其他变量具有更高的显著性，因此提高了国际预后指数的预测价值。本研究提示，TNFγ和p55-R-TNF水平升高与淋巴瘤患者的其他不良预后因素高度相关，可能预示不良预后。
