Alterations of routine blood tests in adult patients with soft tissue sarcomas: Relationships to cytokine serum levels and prognostic significance

Abstract

Background: It has been reported that malignancy is often accompanied by hematological alterations and that such alterations may correlate with poor prognosis. It has also been demonstrated that several cytokines may be synthesized by many malignant tumors and that elevated serum levels of some cytokines are associated with changes in blood cell counts in cancer patients. However, so far little is known about the prognostic significance and mechanism of hematological changes in soft tissue sarcomas. The aim of the study was to evaluate the routine blood tests of disturbances in patients with malignant soft-tissue tumors prior to treatment and to correlate these results with selected cytokine serum levels, clinico-pathological features of the tumors and patient survival. Patients and methods: 145 patients (75 males, 70 females; mean age 49.97 ± 16.9 yrs) with histologically confirmed soft tissue sarcomas before treatment were enrolled into the study. In all these patients we evaluated routine blood tests (hemoglobin level HGB, white blood cell count WBC, platelet count PLT, white blood cell differential count-neutrocyte count NE, lymphocyte count LY, monocyte count MN, eosinophile count EO) and serum levels of 13 cytokines and soluble cytokine receptors (IL-6, IL-8, IL-10, TNFα, G-CSF, M-CSF, bFGF, VEGF, IL-1ra, sIL-2R, sIL-6R, TNF RI, TNF RII) - ELISA method. Peripheral blood samples from 50 healthy volunteers served as control. Statistical analysis was performed using Kolmogorov-Smirnov and Mann-Whitney U-tests, χ2 test (P < 0.05), where appropriate. For survival analysis the Kaplan-Meier method, log-rank test and multivariate Cox analysis were applied. Results: Alterations of at least one of the standard blood tests were found in 43.4% of all cases. The most frequent alterations were: neutrophilia (28.3% of cases), leukocytosis (27.6%), decreased HGB (25.5%), monocytosis (19.3%) and thrombocytosis (14.5%); they correlated strongly with elevated serum levels of several cytokines and soluble cytokine receptors (particularly: sIL-2R, IL-6, IL-8, M-CSF, VEGF, TNF RI, TNF RII) (P < 0.001). Lymphocytopenia (LY < 1.0) found in 10.3% of patients correlated strongly with increased serum levels of IL-6, sIL-2R, TNF RI. In parallel, we found a significant difference in serum levels of 11 of 13 cytokines (IL-1ra, sIL-2R, IL-6, IL-8, IL-10, TNF RI, TNF RII, TNFα, M-CSF, bFGF, VEGF) (P < 0.001) in soft tissue sarcoma patients compared to healthy controls. Hematological alterations were significantly more frequent in patients with advanced tumors. In multivariate analysis we found no prognostic significance of any of the routine blood tests in soft tissue sarcoma patients. Conclusion: The results of this study demonstrate that hematological alterations, which occur in over 40% of soft tissue sarcoma cases, are found more frequently in patients with advanced tumors. Strong correlations between the occurrence of hematological abnormalities and elevated serum levels of several cytokines and soluble cytokine receptors, suggest that the former may develop as a result of cytokine misbalance frequently detected in soft tissue sarcoma patients. However, the results of routine blood tests alone are no independent prognostic factor for survival of soft-tissue sarcoma patients.