Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Treatment of Newly Diagnosed AML
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.[1,2,3,4,5] 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.[2,3,4,5] 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.
Undifferentiated embryonal sarcoma of the liver is so rare that only small series have been published regarding treatment. However, use of aggressive chemotherapy regimens seems to have improved the overall survival (OS). The generally accepted approach is to resect the primary tumor mass in the liver when possible. Neoadjuvant chemotherapy can be effective in decreasing an unresectable primary tumor mass, resulting in resectability.[1,2,3,4] The OS of these children appears...
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. 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.[3,6,7] The United Kingdom Medical Research Council (MRC) 10 Trial compared induction with cytarabine, daunorubicin, and etoposide (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 anthracycline that has been most used in induction regimens for children with AML is daunorubicin,[3,6,7] though idarubicin and the anthracenedione mitoxantrone have also been used.[9,10] Randomized trials have attempted to determine whether any other anthracycline or anthracenedione is superior to daunorubicin as a component of induction therapy for children with AML. The German Berlin-Frankfurt-Munster (BFM) Group AML-BFM 93 study evaluated cytarabine plus etoposide with either daunorubicin or idarubicin (ADE or AIE) and observed similar EFS and OS for both induction treatments.[7,9] The MRC-LEUK-AML12 clinical trial studied induction with cytarabine, mitoxantrone, and etoposide (MAE) in children and adults with AML compared to a similar regimen using daunorubicin (ADE).[10,11] For all patients, MAE showed a reduction in relapse risk, but the increased rate of treatment-related mortality observed for patients receiving MAE led to no significant difference in disease-free survival or OS in comparison to ADE. Similar results were noted when analyses were restricted to pediatric patients. 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.