Clinical implications of angiogenic factors in patients with hematological malignancies: HGF levels have a prognostic impact especially in patients with AML

Abstract

6614 Background: Angiogenesis may have a role in the pathophysiology of hematological malignancies and also be a therapeutic target. Increased levels of angiogenic factors have been correlated with poor prognosis in several solid tumors. Accordingly, we evaluated the serum level of variable angiogenic factors and analyzed their prognostic significance in newly diagnosed patients with hematological malignancies. Methods: The ELISA were performed to quantify basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), tumor necrosis factor-α (TNF-α), angiogenin, and matrix metalloproteinase-9 (MMP-9) in stored samples obtained before treatment from patients with AML (30 patients), ALL (10 patients), CML (14 patients) and MDS (9 patients). Results: VEGF, HGF, angiogenin, and MMP-9 levels were significantly higher in patients with CML than in healthy individuals (p<0.0001 for VEGF, HGF and MMP-9, p=0.024 for angiogenin). HGF levels were also higher in patients with AML than healthy individuals (p<0.001). Higher HGF levels correlated significantly with white blood cell count (p=0.014), monocyte counts (p=0.009), and serum levels of LDH (P=0.009) in AML patients. Among 24 AML patients who received remission induction chemotherapy, 17 patients (70.8%) obtained a complete remission (CR). In univariate analysis, HGF levels (p=0.015) and age (p=0.034) were significant parameters predictive for an achievement of CR. In multivariate analysis using logistic regression model, HGF levels was the only parameter strongly predictive for CR (p=0.047). Leukemia free survival (LFS) for AML patients with lower HGF concentrations was superior to that for those with higher HGF concentrations (1-year LFS rates = 75.0% versus 37.5%, P=0.065). Conclusions: The current study demonstrated elevated serum VEGF, angiogenin, and MMP-9 in patients with CML and elevated serum HGF in patients with CML and AML. The HGF concentrations were significantly correlated with an achievement of CR and high HGF levels were associated with worse survival in patients with AML. No significant financial relationships to disclose.