Tumor-related leukocytosis is linked with poor prognosis in patients with lung carcinoma

Cancer. 2001 Nov 1;92(9):2399-405. doi: 10.1002/1097-0142(20011101)92:9<2399::aid-cncr1588>3.0.co;2-w.


Background: Tumor-related leukocytosis is a paraneoplastic syndrome that is encountered occasionally in the clinical course of patients with lung carcinoma. Recently, autonomous production of hematopoietic cytokines (granulocyte-colony stimulating factor [G-CSF], granulocyte-macrophage-colony stimulating factor [GM-CSF], and interleukin-6 [IL-6]) were identified in some of these patients. However, the incidence and clinical characterization of this phenomenon have not been clarified.

Methods: During a 7-year period, 227 patients with carcinoma of the lung were investigated, and 33 patients were diagnosed with tumor-related leukocytosis. Except for one patient with small cell lung carcinoma, the other 32 patients had nonsmall cell lung carcinoma, and the highest incidence is recognized in large cell carcinoma. These 33 patients were examined for serum G-CSF, GM-CSF, and IL-6 levels using enzyme immunoassays and enzyme-linked immunosorbent assays. Tumor specimens were stained for antihuman cytokine (G-CSF, GM-CSF, and IL-6) monoclonal antibodies.

Results: Sixteen patients showed high serum G-CSF levels, 4 patients showed high serum GM-CSF levels, and 18 patients showed high serum IL-6 levels. Twelve specimens stained positively against anti-G-CSF antibody. Two specimens stained positively against anti-GM-CSF antibody, and three specimens were stained positively against anti-IL-6 antibody, including one double positive specimen for both G-CSF and IL-6. All specimens that were positive for monoclonal antibodies were from patients with nonsmall cell lung carcinoma. These patients had a poor outcome compared with the other patients.

Conclusions: Tumor-related leukocytosis and cytokine production frequently occur in the clinical course of lung carcinoma, and this phenomenon is related mainly to nonsmall cell lung carcinoma. Its occurrence appears to be an ominous prognostic sign in patients with lung carcinoma.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Non-Small-Cell Lung / complications*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Small Cell / complications*
  • Carcinoma, Small Cell / pathology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Granulocyte Colony-Stimulating Factor / analysis
  • Granulocyte Colony-Stimulating Factor / blood
  • Granulocyte-Macrophage Colony-Stimulating Factor / analysis
  • Granulocyte-Macrophage Colony-Stimulating Factor / blood
  • Humans
  • Immunoenzyme Techniques
  • Interleukin-6 / analysis
  • Interleukin-6 / blood
  • Leukocytosis / etiology*
  • Leukocytosis / immunology
  • Lung Neoplasms / complications*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Survival Analysis


  • Antibodies, Monoclonal
  • Biomarkers, Tumor
  • Interleukin-6
  • Granulocyte Colony-Stimulating Factor
  • Granulocyte-Macrophage Colony-Stimulating Factor