Elevated circulating levels of tumor necrosis factor predict unresponsiveness to treatment with interferon alfa-2b in chronic myelogenous leukemia.
OBJECTIVE
The study was undertaken to analyze circulating tumor necrosis factor (TNF) levels in patients with chronic-phase chronic myelogenous leukemia (CML) undergoing interferon (IFN) alfa-2b therapy, and to correlate pretreatment serum levels of TNF with response to IFN alfa-2b therapy.


METHODS
Fourteen patients with CML in chronic phase were treated with recombinant human IFN alfa-2b for 7 to 39 months.


RESULTS
In eight patients IFN alfa-2b treatment failed due to lack of hematologic response. A complete or partial hematologic remission was achieved in the remaining six patients, of whom two patients experienced a complete cytogenetic response. Retrospective analysis of serum samples obtained from all patients before the onset of IFN alfa-2b administration revealed that levels (mean +/- SEM) of circulating TNF were higher (P less than .001) in the group of patients who did not respond to IFN alfa-2b treatment (157 +/- 15 U/mL) than in the responders (10.3 +/- 4 U/mL) or healthy control subjects (9.1 +/- 3 U/mL). However, there was no correlation between TNF serum levels and other patient characteristics at study enrollment including age, sex, duration of disease, performance status, splenomegaly, WBC count, platelet count, hemoglobin value, prior therapy, and prognostic category.


CONCLUSIONS
These findings indicate that circulating levels of TNF are increased in a subset of patients with chronic-phase CML and that this elevation is associated with poor response to IFN alfa-2b therapy.
Herrmann
F
F
Department of Internal Medicine 1, University of Freiburg, Germany.
Helfrich
S G
SG
Lindemann
A
A
Schleiermacher
E
E
Huber
C
C
Mertelsmann
R
R
D000328:Adult; D000368:Aged; D004351:Drug Resistance; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011994:Recombinant Proteins; D012189:Retrospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha