W. Ruka et al., Alterations of routine blood tests in adult patients with soft tissue sarcomas: Relationships to cytokine serum levels and prognostic significance, ANN ONCOL, 12(10), 2001, pp. 1423-1432
Background: It has been reported that malignancy is often accompanied by he
matological alterations and that such alterations may correlate with poor p
rognosis. It has also been demonstrated that several cytokines may be synth
esized by many malignant tumors and that elevated serum levels of some cyto
kines are associated with changes in blood cell counts in cancer patients.
However, so far little is known about the prognostic significance and mecha
nism of hematological changes in soft tissue sarcomas. The aim of the study
was to evaluate the routine blood tests of disturbances in patients with m
alignant soft-tissue tumors prior to treatment and to correlate these resul
ts with selected cytokine serum levels, clinicopathological 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 treat
ment were enrolled into the study. In all these patients we evaluated routi
ne blood tests (hemoglobin level HGB, white blood cell count WBC, platelet
count PLT, white blood cell differential count-neutrocyte count NE, lymphoc
yte count LY, monocyte count MN, eosinophile count EO) and serum levels of
13 cytokines and soluble cytokine receptors (IL-6, IL-8, IL-10, TNF alpha,
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 contr
ol. Statistical analysis was performed using Kolmogorov-Smirnov and Mann-Wh
itney U-tests, chi (2) test (P < 0.05), where appropriate. For survival ana
lysis 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 (2
8.3% of cases), leukocytosis (27.6%), decreased HGB (25.5%), monocytosis (1
9.3%) and thrombocytosis (14.5%); they correlated strongly with elevated se
rum levels of several cytokines and soluble cytokine receptors (particularl
y: sIL-2R, IL-6, IL-8, M-CSF, VEGF, TNF RI, TNF RII) (P < 0.001). Lymphocyt
openia (LY < 1.0) found in 10.3% of patients correlated strongly with incre
ased serum levels of IL-6, sIL-2R, TNF RI. In parallel, we found a signific
ant difference in serum levels of 11 of 13 cytokines (IL-1ra, sIL-2R, IL-6,
IL-8, IL-10, TNF RI, TNF RII, TNF<alpha>, M-CSF, bFGF, VEGF) (P < 0.001) i
n soft tissue sarcoma patients compared to healthy controls. Hematological
alterations were significantly more frequent in patients with advanced tumo
rs. 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 altera
tions, which occur in over 40% of soft tissue sarcoma cases, are found more
frequently in patients with advanced tumors. Strong correlations between t
he occurrence of hematological abnormalities and elevated serum levels of s
everal cytokines and soluble cytokine receptors, suggest that the former ma
y develop as a result of cytokine misbalance frequently detected in soft ti
ssue sarcoma patients. However, the results of routine blood tests alone ar
e no independent prognostic factor for survival of soft-tissue sarcoma pati
ents.