Childhood Acute Myeloid Leukaemia (C-AML)

In the UK, around 2,300 people are diagnosed with AML each year. Of these, only 70 are children.

Acute myeloid leukaemia (AML) is a blood cancer of the bone marrow’s myeloid cells. Acute leukaemias are so called because they develop rapidly and are aggressive types of leukaemia. This is in contrast to chronic leukaemias which develop, and usually progress, slowly.

Acute leukaemias are classified as AML or acute lymphoblastic leukaemia (ALL) depending on whether the origin of the leukaemia cells is myeloid or lymphoid, respectively.

AML is divided into four groups in the 2016 World Health Organisation (WHO) Classification. These four groups of AML and the proportion of children affected are shown below:

  • AML with genetic abnormalities: 52.3%
  • AML with myelodysplasia-related changes: 18.6%
  • AML, not otherwise specified: 22.0%
  • AML associated with Down’s syndrome: 7.0%

The WHO classification is based on the appearance of the AML cells under the microscope, as well as genetic (chromosome and/or genes) changes in the AML cells.

The group AML associated with Down’s syndrome is specific to infants and children. In children with Down’s syndrome who are less than four years of age, up to 70% of children may have AML. However, children with Down’s syndrome who have AML have a better response to chemotherapy and a better prognosis compared with children who have other types of AML.

You can watch Jenson’s story above.

What causes childhood AML?

The origin of the AML cells is thought to be the myeloid stem cells in the bone marrow. A stem cell is the most basic cell in the body that has the ability to develop into any of the body’s specialised cell types, from muscle cells to brain cells. However, what makes these stem cells reproduce uncontrollably in the case of AML is thought to be linked to genetic abnormalities, both in the chromosomes and the genes.

Common chromosome abnormalities seen in children with AML include t(8;21), t(15;17), t(9;11) and t(16;16).

AML in children with Down’s syndrome

Children with Down’s syndrome have a particular type of AML which forms a group of its own in the WHO classification known as AML associated with Down’s syndrome.

Children with Down’s syndrome have an extra whole or partial copy of chromosome 21 (trisomy 21) which is strongly thought to be linked to AML. Compared with the general population, children with Down’s syndrome have a 150-fold increased risk of developing AML and a 500-fold increased risk of developing acute megakaryoblastic leukaemia (AMKL).

Gene mutations

Approximately 20% of children with AML have normal chromosomes; however, they do have mutation genes.

Children with acute promyelocytic leukaemia (APL) do not have a chromosome abnormality but they do have the well-established abnormal PML-RARA gene. In these children, the promyelocytic leukaemia protein (PML) gene on chromosome 15 and the retinoic acid receptor alpha (RARA) gene on chromosome 17 swap in a translocation and fuse to become the PML-RARA gene. Demonstration of this gene in patients establishes the diagnosis of APL.

Other gene mutations seen in children with AML include the following genes:

  • TP53 (tumour suppressor 53)
  • FLT3-ITD (FMS-like tyrosine kinase 3 – internal tandem duplication)
  • NPM1 nucleophosmin
  • RUNX1 (runt-related transcription factor 1)
  • GATA2 (GATA binding protein 2)
  • CEBPA (CCAAT-enhancer binding protein alpha)

GATA2 and CEBPA are often found in families and are linked to AML with myelodysplasia-related changes.

Other factors

As well as chromosomal abnormalities, increased parental age, high birth weight and exposure during pregnancy to radiation, pesticides and hair dyes have been linked with the development of AML in children.

Signs and symptoms

Signs and symptoms of AML are the result of the overcrowding caused by the increased number of leukaemia cells in the bone marrow. As a result, the low levels of red blood cells, platelets and white blood cells can cause anaemia, bleeding and an increased number of infections, respectively.

Specific symptoms include:

  • Anaemia
  • Pale appearance
  • Tiredness
  • Breathing faster to compensate for the anaemia (reduced ability to carry oxygen)
  • Bleeding and/or bruising
  • Petechia (flat, pinpoint spots under the skin caused by bleeding)
  • Recurrent infections

Specific symptoms of infections include:

  • Fever – a raised temperature of 38°C or higher
  • Sore throat
  • Diarrhoea
  • Cough
  • Excessive tiredness
  • Bone and joint pain due to an overcrowded bone marrow
  • Abdominal pain as the leukaemia cells collect in the liver and spleen causing enlargement of these organs and pain
  • Loss of appetite and weight

Children below the age of two years have other distinct clinical characteristics compared to older children:

  • Higher white blood cell count at diagnosis
  • Greater involvement of the central nervous system (CNS), which is made up of the brain and spinal cord
  • Spread of the leukaemia outside the bone marrow, usually in the skin


As with adults, a diagnosis of AML in children requires examination of a blood or bone marrow sample, chromosome analysis, immunophenotyping analysis, and a specific genetics test in the bone marrow for chromosome/gene abnormalities. If your child is very unwell, the initial diagnostic tests may be done using the blood rather than performing a bone marrow aspirate.

  • Blood, bone marrow and cerebrospinal fluid sample analysis – Using the blood sample, a full count of the number of red cells, white cells and platelets is carried out, including a breakdown of the different white cell types to determine which white cells are involved. Examination of a bone marrow sample/cerebrospinal fluid is the most important test for diagnosing AML, particularly for the diagnosis of AML, not otherwise specified. A sample of bone marrow is taken from the hip bone, generally under local anaesthetic, and examined to determine the number and type of cells present and if they are developing normally.
  • Immunophenotyping – Immunophenotyping is a method used to determine the type and number of leukaemia cells present in the blood and bone marrow sample. Immunophenotyping is routinely performed by flow cytometry which processes blood or bone marrow fluid and counts the number of leukaemia cells with the tagged antibodies. The flow cytometer can rapidly measure the number and size of thousands of cells. This also enables a count of the number of leukaemia cells as a proportion of normal cells.
  • Chromosome analysis – The study of the abnormalities in the chromosomes and genes of children with AML is important not only to establish the diagnosis, but also for the classification of AML and estimating the risk of the AML.
  • Risk grouping – Risk classification is based mainly on the chromosome/gene analysis. Depending on the children’s chromosome/gene analysis, they can be grouped into three risk groups: high, intermediate and low. This corresponds to their risk of relapsing.
  • Imaging – X-rays, ultrasound or scans are used to assess and monitor the impact of the AML on the organs of the body. Children who will receive anthracycline chemotherapy such as daunorubicin require a heart scan to evaluate their heart function before starting treatment to determine that their heart can tolerate this treatment. Computer tomography (CT) scans and magnetic resonance imaging (MRI) are used where appropriate.


Treatment for childhood AML common to adults

For most types of AML, induction treatment to achieve remission of the AML can be achieved with a combination of an intensive anthracycline (daunorubicin or idarubicin) and cytarabine chemotherapy.

Liposomal cytarabine-daunorubicin (Vyxeos, CPX-351) is a new drug containing daunorubicin and cytarabine combined in tiny fat droplets called liposomes. These liposomes protect the drugs from being broken down early, so they remain in the body longer. It is also thought that the liposomes build up in the bone marrow to enhance their effect on the leukaemia cells.

Liposomal cytarabine-daunorubicin is available for prescription to children under an ‘orphan designation’, which is a category for products that are still under investigation but are considered to be of benefit to patients. Clinical trials of liposomal cytarabine-daunorubicin in children are ongoing.

Consolidation therapy is used to eradicate any remaining leukaemia cells in the body, which is also called minimum residual disease. Consolidation therapy lessens the risk of relapse. It can be achieved using the same treatment as induction, or by performing a stem cell transplant (SCT) in carefully chosen patients with high-risk AML, or those slow to respond to treatment.

Drugs which target particular genes (targeted drugs) such as the FLT3 inhibitor, midostaurin, can be added to the induction/consolidation treatment to enhance treatment efficacy and help decrease side effects. However, despite the introduction of FLT3 inhibitors, a number of patients with AML will still have to undergo a SCT.

For children and adults with APL, immediate treatment with all-trans retinoic acid (a vitamin A derivative) and arsenic trioxide achieves very good results. APL should not be treated with anthracycline and cytarabine chemotherapy as it can cause serious bleeding.

For relapsed AML (which has returned after initial remission), or refractory AML (which did not respond to initial treatment), another cycle of treatment with the same or another treatment can be given. Alternatively, in these patients and those at high risk of relapse due to their chromosome abnormality, a SCT can be performed.

Central nervous system treatment for patients where leukaemia cells have spread to the brain and spinal cord consists of chemotherapy (two cycles of cytarabine 40 to 50mg) injected directly into the cerebrospinal fluid to kill any remaining leukaemia cells.

Supportive treatment, which is not active treatment but a treatment to maintain quality of life, concentrates on treating any symptoms or complications that arise. It can include blood and platelet transfusions, administration of hydroxycarbamide, eye drops and antibodies. Heart scans are performed to check your child’s heart function.

Treatment for childhood AML different to adults

There are several differences between children and adults which impact on the treatment and outcome of children with AML compared with adults.

Children under the age of two

Characteristics for children under the age of two which affect their treatment are as follows:

  • They have greater risk for relapse due to their genetic abnormalities such as complex multiple chromosome abnormalities, deletion of chromosome 5, deletion of chromosome 7 and abnormalities of chromosome 11. These are present in 42% of children under the age of two.
  • They have greater incidence of leukaemia cells spreading to the brain and spinal cord which requires specific treatment, but this does not affect the outcome for these children. CNS AML is present in approximately 5% to 10% of children at the time of diagnosis or at relapse.
  • They are highly susceptible to infections and often have high white cell counts at diagnosis, and therefore require antibiotic and hydroxycarbamide treatment.
  • They are more susceptible to heart damage when treated with anthracyclines. Additionally, some chemotherapy drugs such as arsenic trioxide used for APL can have cardiovascular side effects which worsens heart disease.
  • On the positive side, they have a greater ability than adults to withstand the high doses of chemotherapy required to induce remission and for SCT preparation. This is reflected in a high overall survival of approximately 70%.

Children with AML/AMKL associated with Down’s syndrome

Children under the age of four years with AML/AMKL associated with Down’s syndrome tend to have a much better response to chemotherapy compared with children with AML/AMKL, but not Down’s syndrome, and adults. However, children with Down’s syndrome are more susceptible to the toxic side effects of the chemotherapy.

Children with AML/AMKL and Down’s syndrome are usually very sensitive to chemotherapy. With treatments tailored according to their needs, excellent survival rates of 80% are possible in these children.

Children over the age of two Incidence of the chromosomal abnormalities

Children over the age of two years have a greater incidence of the more treatable chromosomal abnormalities compared with infants and adults. Chromosomal abnormalities which show a better response to treatment such as t(8;21), t(16;16), and t(15;17) are present in 33% of children aged two to 18 years.

Chromosomal abnormalities which are associated with a poor outcome are lower in children and adolescents and present in less than 22% of children aged two to 18 years.

Side effects

Unfortunately, treatments such as chemotherapy do come with some side effects as they damage healthy cells as well as cancer cells.

It’s difficult to predict exactly which side effects your child will experience as they vary with each drug. However, they are usually temporary.

Short term side effects

Short term side effects can last for a few days or weeks, but for some, can last for the duration of treatment. Side effects your child may experience include:

  • Hair loss
  • Nausea and vomiting
  • Weight loss
  • Fatigue
  • Infection – all patients with AML will at some point get an infection which requires treatment with antibiotics
  • Bleeding and bruising – chemotherapy can make your child more prone to bruising and bleeding

Long term side effects

Long term effects can be a result of chemotherapy but depends on the drugs used.

Loss of fertility

Some of the drugs used to treat AML can affect your child’s fertility in later life and their chances of conceiving in the future.

Your child’s medical team will talk to you about this in more detail before they start treatment and your child will have the chance to discuss this with their healthcare team as they mature and develop into adulthood.

It’s natural to worry about the effects of treatment on any children your child might have after their treatment. However, evidence from clinical studies has shown that any cancer treatment a parent has doesn’t lead to an increased risk of cancer or other health problems in their children.

What happens next?

Once your child’s treatment is finished, they’ll need to have regular check-ups at the hospital. These will be frequent at first, probably one to two months, then every few months until they become yearly at five years and onwards. The purpose of follow-up is to monitor your child and look for signs of relapse or complications.

If you notice any new symptoms or something is worrying you, you should contact your child’s medical team as soon as possible.

New treatments and treatments on the horizon

The number of new drugs available for treating childhood AML is increasing. There are several new types of drugs being studied for the treatment of AML. Most of these fall into the following groups:

  • Immunomodulatory drugs (IMiDs) – Immunomodulatory drugs have been widely used to treat other forms of blood cancer and are now being studied for use in AML. The way in which they work is not fully understood but they affect the immune system. They are mostly being studied in adults but, if results are promising, they may be used to treat childhood AML.
  • Histone deacetylase inhibitors – These are drugs which interfere with the way in which AML cells switch genes on and off.
  • Targeted therapies – These work in different ways but they all targeted to specifically attack the leukaemia cell, whereas most other chemotherapy drugs affect normal cells too. One type of targeted therapy is the use of antibodies to carry chemotherapy drugs directly to the leukaemia cell. Another type attacks weak points of leukaemia cells.
  • FLT3 and IDH inhibitors – FLT3 and IDH are two of the most common genes to become abnormal in AML. A number of drugs have been developed that target these genes.

Questions to ask your medical team about Childhood AML

We understand going through a blood cancer journey can be difficult. It may help to talk to a close friend or relative about how you are feeling. Here are some questions that may be useful to ask your child’s doctor.

  • How would I know if my child has AML?
  • What tests will my child need to have?
  • What will the tests show?
  • How long will the results take?
  • How rare is childhood AML?
  • What sort of treatment will my child need?
  • How long will my child’s treatment last?
  • What will the side effects be?
  • Is there anything my child should or shouldn’t eat?
  • Where can I get help dealing with my child’s and/or my feelings?

Further downloads

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Published: May 2020

Review date: May 2023