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Chemotherapy
Source: Childhood Acute Myeloid Leukemia Treatment (PDQ®)–Health Professional Version, National Cancer Institute.
Source updated: April 15, 2025 · Captured 2026-09-09.
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Context: Treatment of Childhood AML / Induction Therapy
Common induction therapy regimens in children with AML use cytarabine and an anthracycline in combination with other agents such as etoposide and/or thioguanine.[5-7]
Evidence (induction chemotherapy regimen):
The United Kingdom Medical Research Council (MRC) AML10 trial compared induction with cytarabine, daunorubicin, and etoposide (ADE) versus induction with cytarabine, daunorubicin, and thioguanine.[8]
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The United Kingdom Medical Research Council (MRC) AML10 trial compared induction with cytarabine, daunorubicin, and etoposide (ADE) versus induction with cytarabine, daunorubicin, and thioguanine.[8]
There was no difference in remission rate or disease-free survival (DFS) between the thioguanine and etoposide arms, although the thioguanine-containing regimen was associated with increased toxicity.
The MRC AML15 trial demonstrated the following results:[9]
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The MRC AML15 trial demonstrated the following results:[9]
Induction with daunorubicin and cytarabine resulted in equivalent survival rates when compared with ADE induction.
The anthracycline that has been most used in induction regimens for children with AML is daunorubicin,[5-7] although idarubicin and the anthracenedione mitoxantrone have also been used.[1,10,11] 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. In the absence of convincing data that another anthracycline or mitoxantrone produces superior outcome over 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.
Evidence (daunorubicin vs. other anthracyclines):
The German Berlin-Frankfurt-Münster (BFM) Group AML-BFM 93 study evaluated cytarabine plus etoposide with either daunorubicin or idarubicin (ADE or AIE).[6,10]
The German Berlin-Frankfurt-Münster (BFM) Group AML-BFM 93 study evaluated cytarabine plus etoposide with either daunorubicin or idarubicin (ADE or AIE).[6,10]
Similar event-free survival (EFS) and overall survival (OS) rates were observed for both induction treatments.
The MRC-LEUK-AML12 (NCT00002658) clinical trial studied induction with cytarabine, mitoxantrone, and etoposide (MAE) in children and adults with AML compared with ADE.[1,12]
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The MRC-LEUK-AML12 (NCT00002658) clinical trial studied induction with cytarabine, mitoxantrone, and etoposide (MAE) in children and adults with AML compared with ADE.[1,12]
For all patients, the MAE regimen produced a reduction in relapse risk, but the increased rate of treatment-related mortality observed for patients receiving MAE led to no significant difference in DFS or OS rates when compared with ADE.[12]
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The MRC-LEUK-AML12 (NCT00002658) clinical trial studied induction with cytarabine, mitoxantrone, and etoposide (MAE) in children and adults with AML compared with ADE.[1,12]
Similar results were noted when analyses were restricted to pediatric patients.[1]
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The AML-BFM 2004 (NCT00111345) clinical trial compared liposomal daunorubicin (L-DNR) with idarubicin at a higher-than-equivalent dose (80 mg/m2 vs. 12 mg/m2 per day for 3 days) during induction.[13]
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The AML-BFM 2004 (NCT00111345) clinical trial compared liposomal daunorubicin (L-DNR) with idarubicin at a higher-than-equivalent dose (80 mg/m2 vs. 12 mg/m2 per day for 3 days) during induction.[13]
Five-year OS and EFS rates were similar in both treatment arms.
The AML-BFM 2004 (NCT00111345) clinical trial compared liposomal daunorubicin (L-DNR) with idarubicin at a higher-than-equivalent dose (80 mg/m2 vs. 12 mg/m2 per day for 3 days) during induction.[13]
Treatment-related mortality was significantly lower with L-DNR than with idarubicin (2 of 257 patients vs. 10 of 264 patients).
The COG AAML1031 (NCT01371981) trial used mitoxantrone with high-dose cytarabine in its second cycle of induction, following a first cycle of ADE for patients with high-risk AML.[14]
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The COG AAML1031 (NCT01371981) trial used mitoxantrone with high-dose cytarabine in its second cycle of induction, following a first cycle of ADE for patients with high-risk AML.[14]
In a planned comparison with the AAML0531 (NCT00372593) trial, which used a standard ADE regimen in the second induction cycle for similar patients, neither response nor survival was improved, whereas toxicity was increased in patients who received mitoxantrone.
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Although the combination of an anthracycline and cytarabine is the basis of initial standard induction therapy for adults and children, there is evidence that alternative drugs can be used to reduce the use of anthracyclines when necessary.
Evidence (reduced-anthracycline induction regimen):
In the St. Jude Children's Research Hospital (SJCRH) AML08 (NCT00703820) protocol, patients were randomly assigned to receive either clofarabine/cytarabine (CA) or high-dose cytarabine combined with daunorubicin and etoposide (HD-ADE) for induction I. All patients then received the anthracycline-containing, standard-dose ADE regimen for induction II.[15]
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In the St. Jude Children's Research Hospital (SJCRH) AML08 (NCT00703820) protocol, patients were randomly assigned to receive either clofarabine/cytarabine (CA) or high-dose cytarabine combined with daunorubicin and etoposide (HD-ADE) for induction I. All patients then received the anthracycline-containing, standard-dose ADE regimen for induction II.[15]
Despite a higher rate of minimal residual disease (MRD) in the CA group at day 22 of induction I (47% vs. 35%; P = .04), 3-year EFS and OS rates were similar between the two groups.
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).[16] The MRC has intensified induction therapy by prolonging the duration of cytarabine treatment to 10 days.[5]
In adults, another method of intensifying induction therapy is to use 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,[17] a benefit for the use of high-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]
Studies cited in this source section
Source citation is not a determination that a study applies to you.
Publication references
Read the original reference and check its publication notices.
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Preserved source evidence · Not medical advice