title: The clinical significance of tumor necrosis factor-alpha plasma level in patients having chronic lymphocytic leukemia.
abstract: Tumor necrosis factor-alpha (TNF-alpha), 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, TNF-alpha levels were determined in 150 patients with CLL and correlated with disease characteristics, prognostic factors, and survival. The mean TNF-alpha plasma 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 TNF-alpha level had more advanced Rai and Binet stage disease, higher serum beta(2)-microglobulin (beta(2)M) 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 TNF-alpha level (27.5 pg/mL) than patients having a diploid karyotype or other miscellaneous cytogenetic abnormalities (14.2 pg/mL; P <.001). The TNF-alpha level was a predictor of survival when the Cox proportional hazards model was used with TNF-alpha entered as a continuous variable (P =.0001). Also, patients having a TNF-alpha level above the mean value of 14 pg/mL had significantly shorter survival duration (P =.00001). The TNF-alpha level remained predictive of survival in Cox multivariate analysis independent of Rai staging and beta(2)M, hemoglobin, prior therapy, white cell count, and platelet level (P =.005). We conclude that the TNF-alpha level serves as a prognostic factor in patients with CLL and that inhibition of TNF-alpha in these patients could have therapeutic importance.
authors.affiliation: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferrajoli
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Keating
authors.forename: Taghi
authors.initials: T
authors.lastname: Manshouri
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
authors.forename: Amanda
authors.initials: A
authors.lastname: Dey
authors.forename: Zeev
authors.initials: Z
authors.lastname: Estrov
authors.forename: Charles A
authors.initials: CA
authors.lastname: Koller
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Thomas
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Susan
authors.initials: S
authors.lastname: Lerner
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Maher
authors.initials: M
authors.lastname: Albitar
mesh_terms: D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis; D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11; D002881:Chromosomes, Human, Pair 12; D002886:Chromosomes, Human, Pair 17; D017353:Gene Deletion; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000401:mortality; D008562:Membrane Glycoproteins; D009244:NAD+ Nucleosidase / Q000032:analysis; D009367:Neoplasm Staging; D010976:Platelet Count; D011379:Prognosis; D015996:Survival Rate; D014314:Trisomy; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*; D001613:beta 2-Microglobulin / Q000097:blood
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D006454:Hemoglobins; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D001613:beta 2-Microglobulin; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1