Effect and side effects of treating chronic myeloid leukemia (CML) by imatinib in pediatric patients

Background: Inhibition of the leukemia-specific bcr-abl gene rearrangement by the tyrosine kinase inhibitor (TKI) imatinib mesylate (IMA) has dramatically improved therapy of chronic myeloid leukemia (CML). Study CML-paed-II is active within the GPOH and I-BFM networks recommending IMA as frontline treatment for children since 2007. However, pediatric experience is still limited and besides bcr-abl IMA also inhibits other TKs involved in cell signal transduction of bone metabolism. So far, it is regarded upon as to non-specifically inhibit a) the development of osteoblasts from mesenchymal stem cells b) the activity of mature osteoblasts and c) the differentiation of osteoclasts from monocytes by non selectively inhibiting type-III TKs like c-kit, FLT3, PDGFR, and c-fms.