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.
Mistletoe is a semiparasitic plant that grows on several types of common trees such as apple, oak, pine, and elm. Mistletoe extract has been used since ancient times to treat many ailments (see Question 1).
Mistletoe is one of the most widely studied complementary and alternative medicine therapies in people with cancer. In certain European countries, preparations made from European mistletoe are among the most prescribed drugs for patients with cancer (see Question 1).
Contemporary pediatric AML protocols result in 85% to 90% complete remission rates.[6,7,8] Approximately 3% of patients die during the induction phase, most commonly due to treatment-related complications.[6,7,8] To achieve a complete remission, inducing profound bone marrow aplasia (with the exception of the M3 APL subtype) is usually necessary with currently used combination chemotherapy regimens. 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.[3,9,10] 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, although the thioguanine-containing regimen was associated with increased toxicity.
The anthracycline that has been most used in induction regimens for children with AML is daunorubicin,[3,9,10] although idarubicin and the anthracenedione mitoxantrone have also been used.[6,12,13] 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-Münster (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.[10,12]
The MRC-LEUK-AML12 clinical trial studied induction with cytarabine, mitoxantrone, and etoposide (MAE) in children and adults with AML compared with a similar regimen using daunorubicin (ADE).[6,14] 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.
The AML-BFM 2004 clinical trial compared liposomal daunorubicin (L-DNR) to idarubicin at a higher-than-equivalent dose (80 mg/m2 vs. 12 mg/m2 per day for 3 days) during induction. Five-year results in both treatment arms were similar for both OS and EFS. Treatment-related mortality was significantly lower with L-DNR than idarubicin (2 of 257 patients vs. 10 of 264 patients).