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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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Treatment of CML in Children

Imatinib mesylate has shown a high level of activity in children with CML that is comparable to that observed in adults, with approximately 75% achieving a complete cytogenetic response and with approximately 20% showing an unsatisfactory response to imatinib.[28,29,30,30,30,31] The pharmacokinetics of imatinib mesylate in children appears consistent with prior results in adults.[32] Doses of imatinib mesylate used in phase II trials for children with CML have been 260 mg/m2 to 340 mg/m2, which provide comparable drug exposures as the adult flat doses of 400 mg to 600 mg.[30,31] Because there are no pediatric-specific data regarding optimal timing of monitoring for BCR-ABL transcript levels and for the presence of BCR-ABL kinase domain mutations, the monitoring guidelines described above for adults with CML are reasonable to utilize.

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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WebMD Public Information from the National Cancer Institute

Last Updated: February 25, 2014
This information is not intended to replace the advice of a doctor. Healthwise disclaims any liability for the decisions you make based on this information.
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