Adverse effects of imatinib in children with chronic myelogenous leukemia

Imatinib mesylate (IM) is a selective tyrosine kinase inhibitor and is approved for indefinite treatment of pediatric chronic myelogenous leukemia (CML). Potential side-effects regarding growth failure and bone metabolism have been reported but data are still scarce in pediatric CML.

Six chronic-phase CML children on IM treatment with a median age of 9.87 years (range, 5.33-12.67 years) were enrolled in the study. Growth, bone mineral density (BMD), bone parameters, 25(OH)-vitamin D3 (25-OHD3) and blood tests including parathyroid hormone, insulin-like growth factor-1 (IGF-1), IGF binding protein 3, thyroid function test and sex hormones were assessed.

Median duration of IM treatment was 78.5 months. Height velocity was suppressed during the first 30 months of treatment and improved gradually afterwards. Two patients (33.3%) had decreased lumbar spine BMD z-scores (<1.5 SD). Patients with decreased BMD had higher mean IM exposure time than those with normal BMD. The majority of patients (n = 5) had low 25-OHD3 (<30 ng/mL), but there was no correlation between BMD and 25-OHD3 status. Other blood tests were normal.

This study supports and confirms the need for monitoring the side-effects of IM treatment on growth, bone density and vitamin D status in pediatric CML. Prolonged IM treatment was associated with low BMD without disturbing bone parameters. There was high prevalence of vitamin D insufficiency. Therefore, the beneficial effect of vitamin D supplement should be explored with regard to the effects on height velocity and BMD in CML patients with vitamin D insufficiency.