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Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Chronic Myelogenous Leukemia

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Imatinib mesylate is generally well tolerated in children, with adverse effects usually being mild to moderate and quickly reversible with treatment discontinuation or dose reduction.[30,31] Growth retardation occurs in some children receiving imatinib mesylate.[33] The growth inhibitory effects of imatinib mesylate appear to be most pronounced in prepubertal children compared to pubertal children, and children receiving imatinib mesylate and experiencing growth impairment may show a return to normal growth rates when they reach puberty.[33]

In children who develop a hematologic or cytogenetic relapse on imatinib mesylate or who have an inadequate initial response to imatinib mesylate, determination of BCR-ABL kinase domain mutation status should be considered to help guide subsequent therapy. Depending upon the patient's mutation status, alternative kinase inhibitors such as dasatinib or nilotinib can be considered based on adult experience with these agents.[20,21,34,35,36] A pediatric phase I study of dasatinib showed good tolerance for dasatinib in children at doses used to treat adults with CML,[37] and nilotinib is under investigation in children with CML or Ph chromosome–positive ALL (NCT01077544 [CAMN107A2120]). In the presence of the T315I mutation, which is resistant to all FDA-approved kinase inhibitors, strong consideration should be given to performing an allogeneic transplant.

An important question is the impact of imatinib mesylate treatment on outcome for patients who subsequently proceed to allogeneic HSCT. A retrospective comparison of 145 patients who received imatinib mesylate prior to transplant compared with a historical cohort of 231 patients who did not, showed no difference in early hepatotoxicity or engraftment delay.[38] In addition, overall survival, disease-free survival, relapse, and nonrelapse mortality were similar between the two cohorts. The only factor associated with poor outcome in the cohort that received imatinib mesylate was a poor initial response to imatinib mesylate. Further evidence for a lack of effect of pretransplant imatinib mesylate on posttransplant outcomes was supplied by a report from the Center for International Blood and Marrow Transplant Research comparing outcomes for 181 pediatric and adult subjects with CML in first chronic phase treated with imatinib mesylate before HSCT with that for 657 subjects who did not receive the agent before HSCT.[39] Among the patients in first chronic phase, imatinib mesylate therapy before HSCT was associated with better overall survival. A third report of allogeneic HSCT following imatinib supports the efficacy of the strategy of transplantation of patients with imatinib mesylate failure in first chronic phase; 3-year overall survival was 94% for this group (n = 37) with approximately 90% achieving a complete molecular remission following HSCT.[13] The available data suggest that imatinib mesylate prior to transplant does not have a deleterious effect on outcome.

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