Data from children with CML on treatment responses (cytogenetic: CyR; molecular: MR, assessed by quantRT-PCR of BCR-ABL transcript rate) and side effects under up-front treatment with imatinib (IMA) are reported. A landmark analysis in pts entering study CML-paed-II in chronic phase exhibited at month 3: no complete haematological response in 2/42 pts; at month 12: no complete CyR in 2/28 pts; at month 18: no major MR in 2/19 pts. Consequently allogeneic transplantation as curative option was postponed for cases becoming intolerant or refractory to IMA. Overall side effects (Leukemia 2006;20:187; Bone Marrow Transplant 2008;42(Suppl.2):S40) were mild and affected 15% of the total cohort. Two pts experienced intolerance and received 2nd generation TKI. As TKI also inhibit c-kit, PDGFR and c-FMS -thus exerting an impact on the differentiation and proliferation of osteoclasts and osteoblasts- disturbances of bone metabolism and longitudinal growth impairment are of special concern in this not yet outgrown cohort [NEJM 2006;354:2006, Blood 2008;111:2538; Haematologica 2008;93:1101; Lancet 2008;372:111; Int J Hematol 2009;89:251; Haematologica 2009;94:1177). In an animal model we exposed juvenile rodents to IMA, studied bone metabolism, ultrastructure and development using dedicated small tomographs for pQCT and micro CT and could mimic side effects as observed in humans.