Treatment of Newly Diagnosed Acute Myeloid Leukemia
The general principles of therapy for children and adolescents with acute myeloid leukemia (AML) are discussed below, followed by a more specific discussion of the treatment of children with acute promyelocytic leukemia (APL) and Down syndrome.
Overall survival (OS) rates have improved over the past three decades for children with AML, with 5-year survival rates now in the 55% to 65% range.[1,2,3,4] Overall remission induction rates are approximately 85% to 90%, and event-free survival (EFS) rates from the time of diagnosis are in the 45% to 55% range.[2,3,4] There is, however, a wide range in outcome for different biological subtypes of AML (refer to the Cytogenetic Evaluation and Molecular Abnormalities section of this summary for more information); after taking specific biological factors of their leukemia into account, the predicted outcome for any individual patient may be much better or much worse than the overall outcome for the general population of children with AML.
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Because of the intensity of therapy used to treat children with AML, patients should have their care coordinated by specialists in pediatric oncology, and should be treated in cancer centers or hospitals with the necessary supportive care facilities (e.g., to administer specialized blood products; to manage infectious complications; to provide pediatric intensive care; and to provide emotional and developmental support).
Contemporary pediatric AML protocols result in 85% to 90% complete remission rates.[3,5,6] Of those patients who do not go into remission, about one-half have resistant leukemia and one-half die from the complications of the disease or its treatment. To achieve a complete remission (CR), inducing profound bone marrow aplasia (with the exception of the M3 APL subtype) is usually necessary. Because induction chemotherapy produces severe myelosuppression, morbidity and mortality from infection or hemorrhage during the induction period may be significant.
The two most effective drugs used to induce remission in children with AML are cytarabine and an anthracycline. Commonly used pediatric induction therapy regimens use cytarabine and an anthracycline in combination with other agents such as etoposide and/or thioguanine.[3,5,6] For example, the Children's Cancer Group (CCG) intensively-timed dexamethasone, cytarabine, thioguanine, etoposide, and rubidomycin (DCTER) and idarubicin (IDA)-DCTER regimens utilized cytarabine, daunorubicin or idarubicin, dexamethasone, etoposide, and thioguanine given as two 4-day treatments separated by 6 days.[3,7] The German Berlin-Frankfurt-Munster Group studied cytarabine plus etoposide with either daunorubicin or idarubicin (ADE or AIE) administered over 8 days.[6,8,9] The United Kingdom Medical Research Council (MRC) 10 Trial compared induction with ADE versus cytarabine and daunorubicin administered with thioguanine (DAT); the results showed no difference between the thioguanine and etoposide arms in remission rate or disease-free survival. The MRC also studied induction with cytarabine, mitoxantrone, and etoposide (MAE) in children and adults with AML. While there was no difference in CR rates comparing the two groups, the incidence of relapse is lower with MAE, but this benefit was offset by greater toxicity and insignificant differences in OS.[2,5,10,11]