Correlation between High Vascular Endothelial Growth Factor-A Serum Levels and Treatment Outcome in Patients with Standard-Risk Acute Lymphoblastic Leukemia: A Report from Children's Oncology Group Study CCG-1962

• Published in: Clinical cancer research Vol. 12; no. 23; pp. 6978 - 6984
• Main Authors: AVRAMIS, Ioannis A, PANOSYAN, Eduard H, DOREY, Fred, HOLCENBERG, John S, AVRAMIS, Vassilios I
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.12.2006
• Subjects: ALL; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Asparaginase; Biological and medical sciences; Child; Child, Preschool; Disease-Free Survival; Enzyme-Linked Immunosorbent Assay; Epidemiology; General aspects; Hematologic and hematopoietic diseases; Humans; Infant; Kaplan-Meier Estimate; Leukemia; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Multivariate Analysis; outcome; Pharmacology. Drug treatments; Precursor Cell Lymphoblastic Leukemia-Lymphoma - blood; Precursor Cell Lymphoblastic Leukemia-Lymphoma - diagnosis; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Predictive Value of Tests; Prognosis; Public health. Hygiene; Public health. Hygiene-occupational medicine; Recurrence; Remission Induction; Risk Factors; Treatment Outcome; Vascular Endothelial Growth Factor A - blood; VEGF-A; Human; Biological fluid; Prognosis; Acute; Malignant hemopathy; Malignant tumor; Epidemiology; Standards; Cancerology; Vascular endothelium growth factor; Treatment; Lymphoproliferative syndrome; Risk factor; Serum; Acute lymphocytic leukemia; Child
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-06-1140

Purpose: Many molecular pathways, including cell cycle control, angiogenesis, and drug resistance, mediate tumor growth and survival. Vascular endothelial growth factor-A (VEGF-A) serum levels <40 and >100 pg/mL have been associated with good and poor prognoses, respectively. Experimental Design: The hypothesis was that serum VEGF-A levels in standard-risk acute lymphoblastic leukemia pediatric patients at induction are predictive of event-free survival (EFS). One hundred seventeen patients were entered in CCG-1962 study and randomized into the native and polyethylene glycolated asparaginase arms. VEGF-A levels were quantified by an ELISA assay. Results: All patients had a decrease in VEGF-A levels by day 14 of induction, but they later dichotomized; EFS group levels remained low and event group levels increased. A correlation exists between high VEGF-A levels at entry to induction and time to event. Moreover, 6-year EFS patients have lower end of induction VEGF-A levels (28 ± 6 pg/mL) than event patients (>100 pg/mL; P < 0.01). Kaplan-Meier curves using various VEGF-A values were produced; with ≤30 at entry into induction (day 0) and ≤60 pg/mL at the end of induction (day 28), patients with low VEGF-A levels had superior EFS ( P < 1e−4). Furthermore, patients who had an increase in VEGF-A during induction (ΔVEGF-positive, days 0-28) were more likely to have an event ( P < 1e−4). Bifurcation by asparaginase treatment arm did not alter these results. Conclusions: These observations strongly support that high VEGF-A levels in induction are an asparaginase treatment–independent predictive marker for EFS. Hence, an anti-VEGF-A therapy should be tested in acute lymphoblastic leukemia.