# Acute myeloid leukaemia in children

Source: https://onco.cc/cancers/aml-paediatric/  
OnCo record `aml-paediatric` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Acute myeloid leukaemia in children carries gene fusions rather than the mutations of ageing, is treated with four or five intensive courses of chemotherapy, and cures around two thirds of children. Adding gemtuzumab ozogamicin lowered relapse in the AAML0531 trial, and the menin inhibitor revumenib is the first targeted drug approved for the KMT2A-rearranged form common in young children.

## Summary

Childhood AML is defined by chromosomal rearrangements: KMT2A fusions in about a fifth, more in infants; the core-binding-factor leukaemias RUNX1::RUNX1T1 and CBFB::MYH11 in about a quarter, with the best prognosis; NUP98 fusions, CBFA2T3::GLIS2 and RBM15::MRTFA in infants and young children, with the worst; and FLT3 internal tandem duplications in about 15 percent, more in adolescents. NPM1, DNMT3A, TP53 and spliceosome mutations, which dominate adult AML, are rare. Down syndrome brings a distinct GATA1-mutated myeloid leukaemia in the first four years of life that is highly curable with reduced chemotherapy. Risk is assigned by these lesions and by flow cytometry measurable residual disease after the first course.

The backbone came from the UK MRC AML10 and AML12 trials of the 1990s, which set four intensive courses of cytarabine and anthracycline-based chemotherapy with no maintenance, and from the Berlin-Frankfurt-Münster and Nordic groups. COG AAML0531 randomised 1,022 children to gemtuzumab ozogamicin, a CD33 antibody-drug conjugate, added to the first induction and second intensification course: three-year event-free survival 53.1 percent against 46.9 percent, driven by lower relapse, with no significant overall survival gain but a clear benefit in children with high CD33 expression; gemtuzumab was approved for newly diagnosed CD33-positive AML in children from one month of age in 2020. AAML1031 found no benefit from adding bortezomib, and showed that sorafenib added to chemotherapy for FLT3-ITD disease with a high allelic ratio improved event-free survival compared with the FLT3-ITD children on AAML0531. Allogeneic transplant in first remission is reserved for high-risk genetics or persistent residual disease, and the European MyeChild01 trial has been settling gemtuzumab dosing and the choice of anthracycline.

Relapse occurs in about a third of children and is cured in about half of them with fludarabine and cytarabine reinduction and transplant. Revumenib, approved in November 2024 for relapsed or refractory KMT2A-rearranged acute leukaemia from the age of one, is the first targeted therapy for the commonest genetic subgroup; gilteritinib for FLT3-mutated disease and venetoclax with cytarabine, which gave responses in the majority of relapsed children in a St Jude phase 1 study, are in paediatric trials. Anthracycline cardiotoxicity is the defining late effect, so dexrazoxane cardioprotection, liposomal anthracyclines and cumulative-dose limits run through every trial, and infection during the profound neutropenia of each course still kills more children than the leukaemia in many centres.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: Childhood AML; Paediatric AML; Pediatric acute myeloid leukemia
- Tags: subtype-page; paediatric
- Group: paediatric
- Burden: Acute myeloid leukaemia is about one in five childhood leukaemias, a few hundred children a year in the United Kingdom and United States; cure rates have climbed from under a third in the 1970s to around two thirds through more intensive chemotherapy and better supportive care.
- Subtypes: Core-binding-factor AML (RUNX1::RUNX1T1, CBFB::MYH11; low risk); KMT2A-rearranged AML (about a fifth; partner-dependent risk; menin inhibitors); FLT3-ITD AML (about 15 percent; sorafenib or gilteritinib added); Infant AML with NUP98, CBFA2T3::GLIS2 or RBM15::MRTFA fusions (high risk); Myeloid leukaemia of Down syndrome (GATA1-mutated; reduced-intensity chemotherapy); Acute promyelocytic leukaemia in children (retinoic acid and arsenic as in adults); Therapy-related and secondary AML in children
- Biomarkers: Karyotype and FISH for recurrent fusions; RNA fusion panel (KMT2A, NUP98, CBFA2T3::GLIS2); FLT3-ITD and allelic ratio; CD33 expression; Flow cytometry MRD after course 1 and course 2; GATA1 mutation in Down syndrome; Germline predisposition (GATA2, RUNX1, CEBPA)

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/aml-paediatric/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/aml-paediatric/#overview [1 subtype, 3 state-of-the-art points]
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/aml-paediatric/#what-it-is [8 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/aml-paediatric/#finding-it [7 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/aml-paediatric/#treating-it [6 settings, 6 decisions with options]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/aml-paediatric/#evidence [7 trials, 4 key papers, 6 milestones]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/aml-paediatric/#science [8 targets, 1 pathway]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/aml-paediatric/where-you-are/ [1 centre, 13 centres in the subtypes]
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/aml-paediatric/#living-with-it [23 questions, 6 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/aml-paediatric/coming/ [14 medicines, 6 trials, 3 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/aml-paediatric/data/ [70 connected records]

## Standard of care

- Induction (two courses): Cytarabine with daunorubicin or mitoxantrone and etoposide; gemtuzumab ozogamicin added to the first course for CD33-positive disease (AAML0531); MRD after course 1. ([Cytarabine](https://onco.cc/drugs/cytarabine/), [Daunorubicin](https://onco.cc/drugs/daunorubicin/), [Mitoxantrone](https://onco.cc/drugs/mitoxantrone/), [Etoposide](https://onco.cc/drugs/etoposide/), [Gemtuzumab ozogamicin](https://onco.cc/drugs/gemtuzumab-ozogamicin/), [COG AAML0531](https://onco.cc/trials/aaml0531/), [Multiparameter flow cytometry MRD](https://onco.cc/technologies/flow-cytometry-mrd/))
- Consolidation (two or three courses): High-dose cytarabine-based courses; no maintenance. ([Cytarabine](https://onco.cc/drugs/cytarabine/), [Etoposide](https://onco.cc/drugs/etoposide/), [Mitoxantrone](https://onco.cc/drugs/mitoxantrone/), [Gemtuzumab ozogamicin](https://onco.cc/drugs/gemtuzumab-ozogamicin/))
- FLT3-ITD: Sorafenib added to chemotherapy for high allelic ratio (AAML1031); gilteritinib in paediatric trials. ([Sorafenib](https://onco.cc/drugs/sorafenib/), [Gilteritinib](https://onco.cc/drugs/gilteritinib/), [FLT3](https://onco.cc/targets/flt3/), [AAML1031](https://onco.cc/trials/aaml1031/))
- High-risk genetics or persistent residual disease: Allogeneic transplant in first remission. ([Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/), [Multiparameter flow cytometry MRD](https://onco.cc/technologies/flow-cytometry-mrd/))
- Relapsed or refractory: Fludarabine and cytarabine reinduction; revumenib for KMT2A-rearranged disease; gilteritinib for FLT3; venetoclax combinations in trials; transplant. ([Fludarabine](https://onco.cc/drugs/fludarabine/), [Cytarabine](https://onco.cc/drugs/cytarabine/), [Revumenib](https://onco.cc/drugs/revumenib/), [AUGMENT-101](https://onco.cc/trials/augment-101/), [Gilteritinib](https://onco.cc/drugs/gilteritinib/), [Venetoclax](https://onco.cc/drugs/venetoclax/), [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/))
- Supportive care and late effects: Dexrazoxane cardioprotection with anthracyclines, transfusion and antimicrobial support, cardio-oncology follow-up. ([Dexrazoxane](https://onco.cc/drugs/dexrazoxane/), [Cardio-oncology](https://onco.cc/technologies/cardio-oncology/), [Transfusion support and anaemia management](https://onco.cc/technologies/transfusion-support/))

## State of the art

- Gemtuzumab ozogamicin added to intensive chemotherapy lowered relapse in AAML0531 and is approved for children from one month of age.
- Revumenib is the first targeted therapy approved for KMT2A-rearranged leukaemia, the commonest genetic subgroup in young children.
- Flow cytometry residual disease after the first course, with genetics, decides who is transplanted in first remission.

## Open problems

- A third of children relapse and only half of those are cured.
- Infant AML with NUP98 or CBFA2T3::GLIS2 fusions has no effective therapy.
- Anthracycline cardiotoxicity and infection deaths from the most intensive chemotherapy given to children.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Acute_myeloid_leukemia
- Wikipedia: Acute myeloid leukaemia: https://en.wikipedia.org/wiki/Acute_myeloid_leukemia
- NCI PDQ: Childhood AML Treatment: https://www.cancer.gov/types/leukemia/hp/child-aml-treatment-pdq

## Connected records

- cancers: [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [Acute promyelocytic leukaemia](https://onco.cc/cancers/apl/), [FLT3-mutated acute myeloid leukaemia](https://onco.cc/cancers/aml-flt3/), [Infant acute lymphoblastic leukaemia (KMT2A-rearranged, under one year)](https://onco.cc/cancers/all-infant/), [Myeloid leukaemia of Down syndrome](https://onco.cc/cancers/myeloid-leukaemia-of-down-syndrome/), [NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia](https://onco.cc/cancers/aml-npm1-kmt2a/), [Secondary and therapy-related acute myeloid leukaemia](https://onco.cc/cancers/aml-secondary/)
- technologies: [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/), [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [Cardio-oncology](https://onco.cc/technologies/cardio-oncology/), [Memory, attention and learning after treatment of a childhood cancer](https://onco.cc/technologies/rejuv-paed-neurocognitive/), [Menin inhibitors](https://onco.cc/technologies/menin-inhibitors/), [Multiparameter flow cytometry MRD](https://onco.cc/technologies/flow-cytometry-mrd/), [The heart after anthracyclines and chest radiotherapy in childhood](https://onco.cc/technologies/rejuv-paed-heart/), [Transfusion support and anaemia management](https://onco.cc/technologies/transfusion-support/)
- targets: [CD33](https://onco.cc/targets/cd33/), [FLT3](https://onco.cc/targets/flt3/), [KMT2A (MLL) rearrangement](https://onco.cc/targets/kmt2a/), [Menin](https://onco.cc/targets/menin/)
- companies: [Children's Oncology Group (COG)](https://onco.cc/companies/childrens-oncology-group/)
- institutions: [St. Jude Children's Research Hospital](https://onco.cc/institutions/st-jude/)
- pathways: [Menin / KMT2A (HOXA9-MEIS1 axis)](https://onco.cc/pathways/menin-kmt2a/)
- terms: [Late effects and survivorship toxicity](https://onco.cc/terms/late-effects/), [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/), [Secondary malignancy (therapy-related cancer)](https://onco.cc/terms/secondary-malignancy/)
- key papers: [AAML0531: gemtuzumab ozogamicin added to chemotherapy for children and adolescents with acute myeloid leukaemia](https://onco.cc/key-papers/paper-aaml0531-gemtuzumab-gamis-jco-2014/), [AAML1031: bortezomib with standard chemotherapy for children with acute myeloid leukaemia does not improve outcomes](https://onco.cc/key-papers/paper-aaml1031-bortezomib-aplenc-haematologica-2020/), [AAML1031: sorafenib combined with chemotherapy for children with high allelic ratio FLT3-ITD acute myeloid leukaemia](https://onco.cc/key-papers/paper-aaml1031-sorafenib-flt3-pollard-jco-2022/), [The molecular landscape of paediatric acute myeloid leukaemia (TARGET)](https://onco.cc/key-papers/paper-bolouri-paediatric-aml-genomics-nat-med-2018/)
- trials: [A Global Study of Midostaurin in Combination With Chemotherapy to Evaluate Safety, Efficacy and Pharmacokinetics in Newly Diagnosed Pediatric Patients With FLT3 Mutated AML](https://onco.cc/trials/nct03591510/), [AAML1031](https://onco.cc/trials/aaml1031/), [AUGMENT-101](https://onco.cc/trials/augment-101/), [COG AAML0531](https://onco.cc/trials/aaml0531/), [Safety and Efficacy of Ponatinib for Treatment of Pediatric Recurrent or Refractory Leukemias, Lymphomas or Solid Tumors](https://onco.cc/trials/nct03934372/), [Safety and Efficacy of Quizartinib in Children and Young Adults With Acute Myeloid Leukemia (AML), a Cancer of the Blood](https://onco.cc/trials/nct03793478/), [Study of Gene Modified Donor T-cells Following TCR Alpha Beta Positive Depleted Stem Cell Transplant](https://onco.cc/trials/nct03301168/)
- drugs: [Bortezomib](https://onco.cc/drugs/bortezomib/), [CPX-351 (liposomal daunorubicin-cytarabine)](https://onco.cc/drugs/cpx-351/), [Cytarabine](https://onco.cc/drugs/cytarabine/), [Daunorubicin](https://onco.cc/drugs/daunorubicin/), [Dexrazoxane](https://onco.cc/drugs/dexrazoxane/), [Etoposide](https://onco.cc/drugs/etoposide/), [Fludarabine](https://onco.cc/drugs/fludarabine/), [Gemtuzumab ozogamicin](https://onco.cc/drugs/gemtuzumab-ozogamicin/), [Gilteritinib](https://onco.cc/drugs/gilteritinib/), [Mitoxantrone](https://onco.cc/drugs/mitoxantrone/), [Revumenib](https://onco.cc/drugs/revumenib/), [Sorafenib](https://onco.cc/drugs/sorafenib/), [Venetoclax](https://onco.cc/drugs/venetoclax/), [Ziftomenib](https://onco.cc/drugs/ziftomenib/)
- biomarkers: [CD33 expression (CD33-positive)](https://onco.cc/biomarkers/cd33-expression/)

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JSON: https://onco.cc/api/v1/entities/aml-paediatric.json