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

Alessandra Ferrajoli, Michael J. Keating, Taghi Manshouri, Francis J. Giles, Amanda Dey, Zeev Estrov, Charles A. Koller, Razelle Kurzrock, Deborah A. Thomas, Stefan Faderl, Susan Lerner, Susan O'Brien, Maher Albitar*

*Corresponding author for this work

Research output: Contribution to journalArticle

136 Scopus citations

Abstract

Tumor necrosis factor-α (TNF-α), 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-α levels were determined in 150 patients with CLL and correlated with disease characteristics, prognostic factors, and survival. The mean TNF-α 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-α level had more advanced Rai and Binet stage disease, higher serum β 2-microglobulin (β 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 TNF-α level (27.5 pg/mL) than patients having a diploid karyotype or other miscellaneous cytogenetic abnormalities (14.2 pg/mL; P < .001). The TNF-α level was a predictor of survival when the Cox proportional hazards model was used with TNF-α entered as a continuous variable (P = .0001). Also, patients having a TNF-α level above the mean value of 14 pg/mL had significantly shorter survival duration (P = .00001). The TNF-α level remained predictive of survival in Cox multivariate analysis independent of Rai staging and β 2M, hemoglobin, prior therapy, white cell count, and platelet level (P = .005). We conclude that the TNF-α level serves as a prognostic factor in patients with CLL and that inhibition of TNF-α in these patients could have therapeutic importance.

Original languageEnglish (US)
Pages (from-to)1215-1219
Number of pages5
JournalBlood
Volume100
Issue number4
StatePublished - Aug 15 2002

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Ferrajoli, A., Keating, M. J., Manshouri, T., Giles, F. J., Dey, A., Estrov, Z., Koller, C. A., Kurzrock, R., Thomas, D. A., Faderl, S., Lerner, S., O'Brien, S., & Albitar, M. (2002). The clinical significance of tumor necrosis factor-α plasma level in patients having chronic lymphocytic leukemia. Blood, 100(4), 1215-1219.