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  • Title: Imatinib mesylate in Philadelphia chromosome-positive leukemia of childhood.
    Author: Kolb EA, Pan Q, Ladanyi M, Steinherz PG.
    Journal: Cancer; 2003 Dec 15; 98(12):2643-50. PubMed ID: 14669284.
    Abstract:
    BACKGROUND: Initial treatment for adult patients with Philadelphia chromosome-positive (Ph[+]) chronic myelogenous leukemia (CML) now includes imatinib mesylate. However, to our knowledge, there are few data regarding imatinib safety, efficacy, and response monitoring in patients age < 18 years. METHODS: In the current series, the authors report 5 consecutive patients ages 20 months to 12 years with Ph+ leukemia who were treated with imatinib and evaluated for a response using cytogenetics, fluorescent in situ hybridization (FISH), and real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) on serial bone marrow aspirations. Doses of imatinib were escalated as tolerated from a starting dose of 400 mg/m2 (patients with a body surface area [BSA] < 1 m2) or 400 mg/day (patients with a BSA > 1 m2). RESULTS: After the initiation of imatinib therapy, all 4 patients with CML were found to have no detectable Ph chromosome by cytogenetics (median of 198 days of imatinib therapy; range, 138-346 days), FISH (median of 285 days of imatinib therapy; range, 138-366 days), and real-time RT-PCR (median of 287 days of imatinib therapy; range, 224-366 days). One patient with Ph+ acute mixed lineage leukemia achieved a morphologic disease remission with standard chemotherapy, but within 10 months had increasing Ph positivity in consecutive bone marrow aspirations. Imatinib was added to the intensive leukemia therapy, and within 26 days there were no detectable Ph+ cells in the bone marrow. Mild thrombocytopenia was noted in two patients and transient mild hepatic toxicity was noted in one patient. CONCLUSIONS: Imatinib mesylate was found to be effective in inducing undetectable residual disease in a small cohort of pediatric patients with Ph+ leukemia. Further studies of the use of imatinib in childhood Ph+ malignancies are needed.
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