The clinical significance of tumor necrosis factor- plasma level in patients having chronic lymphocytic leukemia

Tumor necrosis factor(TNF), a cytokine possessing pleiotropic biological activities, is produced by leukemic lymphocytes in patients with chronic lymphocytic leukemia (CLL) and acts as an autocrine and paracrine growth factor in this disease. In this study, TNFlevels were determined in 150 patients with CLL and correlated with disease characteristics, prognostic factors, and survival. The mean TNFplasma concentration in the patients with CLL was significantly higher than in the healthy control population (16.4 versus 8.7 pg/mL; P < .0001). Patients having an elevated TNFlevel had more advanced Rai and Binet stage disease, higher serum 2-microglobulin ( 2M) levels, a greater percentage of cells expressing CD38, and lower hemoglobin and platelet levels. Patients having chromosomal abnormalities such as 11q deletion, trisomy 12, and chromosome 17 aberrations had a higher mean TNFlevel (27.5 pg/mL) than patients having a diploid karyotype or other miscellaneous cytogenetic abnormalities (14.2 pg/mL; P < .001). The TNFlevel was a predictor of survival when the Cox proportional hazards model was used with TNFentered as a continuous variable (P .0001). Also, patients having a TNFlevel above the mean value of 14 pg/mL had significantly shorter survival duration (P .00001). The TNFlevel remained predictive of survival in Cox multivariate analysis independent of Rai staging and 2M, hemoglobin, prior therapy, white cell count, and platelet level (P .005). We conclude that the TNFlevel serves as a prognostic factor in patients with CLL and that inhibition of TNFin these patients could have therapeutic importance. (Blood. 2002;100:1215-1219)