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Blood, 15 August 2002, Vol. 100, No. 4, pp. 1215-1219
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
The clinical significance of tumor necrosis factor-
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, and
Maher Albitar
From the Departments of Leukemia,
Bioimmunotherapy, and Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston.
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,
TNF- levels were determined in 150 patients with CLL and correlated
with disease characteristics, prognostic factors, and survival. The
mean TNF- 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- level 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
TNF- level (27.5 pg/mL) than patients having a diploid
karyotype or other miscellaneous cytogenetic abnormalities (14.2 pg/mL;
P < .001). The TNF- level was a predictor of survival when the Cox proportional hazards model was used with TNF- entered as a continuous variable (P = .0001). Also, patients
having a TNF- level above the mean value of 14 pg/mL had
significantly shorter survival duration (P = .00001). The
TNF- level 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 TNF- level serves as
a prognostic factor in patients with CLL and that inhibition of TNF-
in these patients could have therapeutic importance.
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