Growth failure in children with chronic myeloid leukemia receiving imatinib is due to disruption of GH/IGF-1 axis.

ABSTRACT

BACKGROUND: The frontline treatment for chronic myeloid leukemia (CML) is tyrosine kinase inhibitor therapy. There is increasing evidence that imatinib results in growth failure in children; etiology is unclear. PROCEDURE The cross-sectional study was conducted from January 2011 to June 2012 in a pediatric oncology unit. Patients with chronic-phase CML, receiving imatinib for more than 6 months were enrolled. Growth hormone (GH) Insulin like growth factor-1 (IGF-1) axis was evaluated by GH stimulation test by insulin tolerance and clonidine stimulation test, among other hormonal assays. RESULTS: Eighteen patients with a median age of 12.9 years (range 6.5-17) completed the study. The mean duration of imatinib therapy was 43.7 ± 32.8 months. The height-for-age z-scores at the start of imatinib and at enrollment were -1.07 ± 0.88 and -1.8 ± 0.98, respectively (P < 0.001). Seven (39%) patients were GH deficient and lacked a sufficient response to either of the two stimulation tests. Majority, 16 (89%) patients had IGF-1 z-scores less than the mean. IGFBP-3 levels were below the mean in all patients. Every patient had deficiency of either GH, or IGF-1, or both. Bone age was delayed in 7 (39%). CONCLUSIONS: This study demonstrates that imatinib results in growth failure in children with CML by disturbing the GHIGF-1 axis. GH stimulation test and serum IGF-1 levels should be performed in children on treatment with imatinib who have growth retardation. Future studies should evaluate the role of recombinant GH therapy for ameliorating the adverse effect on growth.