Imatinib mesylate causes growth deceleration in pediatric patients with chronic myelogenous leukemia

Background: Imatinib mesylate, a tyrosine kinase inhibitor, is used in the treatment of chronic myelogeneous leukemia (CML). Given its ease of administration and manageable side effects in adults, imatinib mesylate was introduced as therapy for pediatric CML. Recently published case reports describe growth deceleration in children treated with imatinib. This study details the growth phenotype of seven pediatric patients maintained in remission on imatnib mesylate over an extended period of time. Procedure: This study is a retrospective chart review of pediatric patients with CML at Oregon Health & Science University treated with imatinib. Height, weight, and body mass index (BMI) measurements were collected before and during treatment. Median standard deviation scores (SDS) were analyzed by Wilcoxon Rank-Sum test and Wilcoxon signed rank cohort analysis. Results: Individual patient analysis demonstrated five of seven subjects with a statistically significant decrease in height SDS pre versus during treatment. The whole group analysis showed a trend to significance for difference in median height SDS pre and during treatment (P=0.078). Bone age was delayed in all four patients in whom bone ages were obtained. IGF-1, IGFBP-3, and thyroid levels during treatment were normal. Four patients experienced an improvement in height SDS during puberty. However, three patients approaching near final adult height failed to achieve genetic height potential determined by mid-parental target height. Conclusion: Growth in children with CML appears to be adversely impacted by imatinib therapy. BMI and IGF-1/IGFBP-3 are maintained during treatment, suggesting a direct effect of imatinib on the growth plate.