Increased serum levels of vascular endothelial growth factor predict risk of progression in early B‐cell chronic lymphocytic leukaemia

Abstract

The present study is the first to evaluate serum levels of vascular endothelial growth factor (VEGF) in B‐cell chronic lymphocytic leukaemia (CLL). All 68 B‐cell CLL patients and 31 control subjects analysed had detectable serum levels of VEGF, with no statistically significant difference between two proups. An aberrant increase of circulating levels of VEGF was found in only 17.6% of cases. B‐cell CLL patients whose serum VEGF levels were higher than the median (i.e. 194.8 pg/ml) or 75th percentile (i.e. 288.5 pg/ml) values were more frequently at an advanced clinical stage. In contrast, no correlation with other clinico‐biological features representative of either tumour mass [bone marrow (BM) histology, peripheral blood (PB) lymphocytosis, beta‐2 microglobulin (β‐2m), LDH, interleukin‐6 (IL‐6)] or disease‐progression (DP) [lymphocyte doubling time (LDT)] was found. Serum levels of VEGF predicted the risk of DP in early CLL. Among 41 patients in Binet stage A, progression‐free survival (PFS) was significantly shorter in those patients whose VEGF serum concentrations were above the median value. Interestingly, characteristics of stage A patients stratified according to the median value of VEGF were similar with respect to many clinico‐biological features, thus suggesting a possible independent prognostic role for such a marker. Finally, when added to the Rai subclassification, VEGF serum levels identified two groups with different PFS within stages I–II. We conclude that increased serum levels of VEGF can be considered useful for predicting the risk of DP and add prognostic information to the Rai subclassification of stage A CLL.

Clinicoprognostic implications of increased serum levels of vascular endothelial growth factor and basic fibroblastic growth factor in early B-cell chronic lymphocytic leukaemia

“…VEGF and b-FGF concentrations were determinated by using a quantitative ELISA technique (Human VEGF and human b-FGF, Quantikine TM and Quantikine 1 ; R&D Systems, Minneapolis, MN, USA) as previously reported (Molica et al, 1999). Concentrations were reported as pg ml 71 .…”

“…Other assays b-2 m and LDH serum levels were determinated as previously described (Molica et al, 1999).…”

“…Elevated pretreatment levels of b-FGF correlate with a more advanced clinical stage and with resistance to chemotherapy (Menzel et al, 1996;Konig et al, 1997), while low cellular and high serum levels of VEGF are associated with a poor clinical outcome (Molica et al, 1999;Aguayo et al, 2000). Although these data lend support to the idea that angiogenic cytokines may play a role in the leukaemogenic process of CLL, the relative merit of VEGF and b-FGF in predicting the outcome of disease has not been assessed thus far.…”

True

“…Higher levels of VEGF in serum or plasma have been evaluated as a predictor of outcome in patients with several malignant diseases (Dirix et al, 1996;Crew et al, 1997;Salven et al, 1997;Kraft et al, 1999;Molica et al, 1999). Recently, it has also been suggested that the patients with metastatic prostate cancer have higher plasma VEGF levels than those with localized disease or healthy controls (Duque et al, 1999).…”

Vascular Endothelial Growth Factor and Platelets

“…In fact, the level of circulating VEGFin peripheral blood has been shown to be associated with angiogenesis, growth, dissemination, metastasis, and poor outcome irLsoHd or hematological malignancies (3)(4)(5)(6). Accordingly, for clinicians, knowledge of measurement of the VEGFlevel in peripheral blood should be emphasized.…”