Insulin-like growth factor-I and insulin-like growth factor binding protein-3 during maintenance chemotherapy of acute lymphoblastic leukemia in children

Purpose: To assess the effect of maintenance chemotherapy (MT) on growth factors and growth in children with acute lymphoblastic leukemia (ALL). Patients and Methods: Twenty-one children (10 girls, 11 boys) with standard risk pre-B ALL treated with chemotherapy had serum insulin-like growth factor-I (IGF-I), serum IGF binding protein-3 (IGFBP-3) levels, and linear growth and weight data measured every 3 months during MT. The levels of the cytotoxic metabolites of methotrexate (MTX) and 6-mercaptopurine (6MP) (i.e., erythrocyte MTX polyglutamates [E-MTX], and erythrocyte B-thioguanine nucleotides [E-6TGN]), s-aminotransferases, and white blood counts (WBC) were measured at least monthly. Results: At the beginning of MT, the median IGF-I standard deviation scores (SDS) and IGFBP-3 SDS were -0.52 and -0.09, respectively, which declined during NIT to -1.67 (P < 0.001) and -1.82 (P < 0.001), respectively. At the time of diagnosis, the median height SDS was -0.4, which declined during MT to a median height SDS of -0.9 at cessation of therapy. No significant correlations were found between growth factor levels, growth and body mass index (BMI) versus the doses of MTX. and 6MP, E-MTX, E-6TGN, s-aminotransferases, or WBC. Conclusions: A significant decline in IGF-I, IGFBP-3, and growth retardation may not be directly related to the treatment intensity during MT.