VEGF Levels Predict Disease Progression in CLL

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[1517] Plasma Levels of Vascular Endothelial Growth

Factor (VEGF) Are Predictive of Disease-Progression in

B-Cell chronic lymphocytic leukemia (B-CLL).

Luca Maurillo, Giovanni Del Poeta, o Venditti,

Suppo Giovanna, Francesco Buccisano, Ilaria Del

Principe, Tamburini, Alessandra Scornajenghi,

Epiceno, a Piccioni, Amadori

Hematology, University Tor Vergata, Rome, Italy

Recent reports have suggested that angiogenesis may be

involved in the pathogenesis of haematological

malignancies.

VEGF is an important proangiogenic factor and high

levels of this protein have been correlated with poor

prognosis in patients (pts) with solid tumors and

acute leukemia; on the contrary, studies of the

expression of VEGF in B-CLL have yielded conflicting

results.

For this reason, we performed immunoenzymatic assays

(R & D systems), to measure plasma VEGF levels in B-CLL

samples from 115 pts and correlated the results with

disease characteristics at the time of sampling and

with prognosis.

The patients' median age was 66 years and M/F ratio

was 1.25; according to Rai staging system 35 were

stage 0, 45 stage I, 28 stage II, 5 stage III and 2

stage IV. The median survival was 42 months; median

follow up from the date of diagnosis was 41 months.

B-CLL pts showed VEGF levels significantly higher than

22 healthy blood donors (55.7±71.9 vs. 8±11.5). No

significant correlation was found between VEGF levels

and other clinico-biological parameters such as age,

sex, clinical stage, number of lymphocytes/L and

platelets/L, lymphocyte doubling time and bcl-2

levels. However, among Rai stages III-IV, 7/7 pts.

showed VEGF values <60 pg/mL.

VEGF levels <60 pg/mL were significantly correlated

with b-2 microglobulin (b-2m) higher than 2.2 mg/mL

and soluble CD23 (sCD23) higher than 60 U/mL (p=0.04

for both features). Pts with VEGF >60 pg/mL had better

survival, although this difference was not

significative. On the contrary, VEGF levels <60 pg/mL

were significantly associated with a worse progression

free survival (PFS).

Moreover, within the Rai 0-I subset VEGF values <60

pg/mL were significantly correlated with high b-2m and

sCD23 values and with a shorter PFS.

In multivariate analysis VEGF was found to be an

independent prognostic factor with regard to PFS

together with CD38 expression and sCD23.

In conclusion our data provide strong evidence that

plasma VEGF level is a major determinant of disease

progression in B-CLL.

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