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    Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Treatment of Newly Diagnosed AML

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    In the absence of convincing data that another anthracycline or mitoxantrone produces superior outcome to daunorubicin when given at an equitoxic dose, daunorubicin remains the anthracycline most commonly used during induction therapy for children with AML in the United States.

    The intensity of induction therapy influences the overall outcome of therapy. The CCG-2891 study demonstrated that intensively timed induction therapy (4-day treatment courses separated by only 6 days) produced better EFS than standard-timing induction therapy (4-day treatment courses separated by 2 weeks or longer).[3] The MRC has intensified induction therapy by prolonging the duration of cytarabine treatment to 10 days.[9] Another way of intensifying induction therapy is by the use of high-dose cytarabine. While studies in nonelderly adults suggest an advantage for intensifying induction therapy with high-dose cytarabine (2-3 g/m2 /dose) compared with standard-dose cytarabine,[16,17] a benefit for the use of high-dose cytarabine compared with standard-dose cytarabine in children was not observed using a cytarabine dose of 1 g/m2 given twice daily for 7 days with daunorubicin and thioguanine.[18] A second pediatric study also failed to detect a benefit for high-dose cytarabine over standard-dose cytarabine when used during induction therapy.[19]

    In children with high-risk AML, the estimated incidence of severe bacterial infections is 50% to 60%, and the estimated incidence of invasive fungal infections is 7.0% to 12.5%.[20,21,22] Several approaches have been examined in terms of reducing the morbidity and mortality from infection in children with AML.

    Hematopoietic growth factors such as granulocyte-macrophage colony-stimulating factor (GM-CSF) or granulocyte colony-stimulating factor (G-CSF) during AML induction therapy have been evaluated in multiple placebo-controlled studies in adults with AML in attempts to reduce the toxicity associated with prolonged myelosuppression.[7,23] These studies have generally shown a reduction of several days in the duration of neutropenia with the use of either G-CSF or GM-CSF [23] but have not shown significant effects on treatment-related mortality or OS.[23] A randomized study in children with AML that evaluated G-CSF administered after induction chemotherapy showed a reduction in duration of neutropenia but no difference in infectious complications or mortality.[24] A higher relapse rate has been reported for children with AML expressing the differentiation defective G-CSF receptor isoform IV.[25] Thus, routine prophylactic use of hematopoietic growth factors is not recommended for children with AML.

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