Abstract
Increased angiogenesis in bone marrow (BM) is one of the characteristics of chronic myeloid leukemia (CML), a clonal myeloproliferative disorder which expresses a chimeric Bcr/Abl protein. The therapeutic strategy in CML has been totally modified with the development of Imatinib Mesylate (STI571), a specific inhibitor of Bcr/Abl tyrosine kinase activity. Previously, we studied the effect of Imatinib on the Vascular Endothelial Growth Factor (VEGF), one of the most potent regulators of angiogenesis (1). Thus, we demonstrated, for the first time, the decrease in VEGF production in CML patients treated with Imatinib. It pointed out the potential prognostic value of determining the VEGF plasma level of patients in order to follow the evolution of this hematologic malignancy. Actually, we showed that low plasma VEGF levels could be one of the characteristics of complete cytogenetic remission.
However, investigations with a larger number of patients were necessary to evaluate the potential of VEGF levels in the monitoring of CML patients treated with Imatinib. So, we analyzed VEGF plasma level in patients treated in the SPIRIT, the CML French Group phase III, multicenter, open-label, prospective trial. Patients are randomized between the 3 experimental arms [IM 400mg daily in combination with Peg-IFN-α2a (Peg-IFNα2a, 90 μg weekly) or with Ara-C (20 mg/m2/day, days 15–28 of 28-day cycles) or IM 600mg daily] and the reference arm, IM 400mg daily. The Endpoint are overall survival (primary), rate and duration of hematologic, cytogenetic and molecular responses and tolerability. This VEGF evaluation is based on a cohort of 110 pts [median age 51 yrs (19–81); Sokal distribution : 30% of pts low, 37% intermediate, and 33% high]. Males predominated (62%) and percentage of patients enrolled in IM 400mg, IM 600mg, IM 400 with Ara-C and IM 400mg with Peg-IFN arm is respectively 28%, 28%, 24% and 30%. At diagnosis, the median of VEGF plasma level is 945 pg/ml (range: 42.3–4001.5). After 3 months of treatment, the median of VEGF level decreases significantly (p<0.05) to 116.4 pg/ml (range: 6.7–2780). After 6, 9, 12 months of treatment, the median of VEGF level was stabilized at respectively 104 pg/ml (range: 17.9–2244.9), 88.3 pg/ml (range: 21.2–907.4), 99 pg/ml (range: 22.1–689,2).
To determine prognosis value of VEGF we correlated the results with the cytogenetic and molecular response.
Vascular Endothelial Growth Factor Receptor Polymorphisms and im Treatment Response in Chronic Myeloid Leukemia Patients
