About childhood acute myeloid leukaemia (AML)
AML is characterised by an overproduction of immature white blood cells, called myeloblasts or leukaemic blasts, but can occasionally occur in the red cell or platelet lines. These cells crowd the bone marrow, preventing it from making normal blood cells. They can also spill out into the bloodstream and circulate around the body. Due to their immaturity they are unable to function properly to prevent or fight infection. Inadequate numbers of red cells and platelets being made by the marrow cause anaemia, easy bleeding, and/or bruising.
The most important factor in predicting prognosis in AML is the genetic make-up of the leukaemic cells. Certain cytogenetic changes are associated with a more favourable prognosis than others. This means that they are more likely to respond well to treatment, and may even be cured. Other cytogenetic changes are associated with an average or intermediate prognosis, while others are associated with a poor, or unfavourable prognosis. It is important to note that in most cases of AML, neither ‘good’ nor ‘bad-risk’ cytogenetic changes are found. People with ‘normal’ cytogenetics are also regarded as having an average prognosis.
What are the subtypes of childhood AML?
Some years ago doctors from America, France, and Britain classified AML into eight different subtypes based on the appearance of the leukaemic cells under the microscope. Each subtype provides information on the type of blood cell involved and the point at which it stopped maturing properly in the bone marrow. This is known as the French-American-British (FAB) classification system.
The current World Health Organisation’s classification system for AML uses additional information obtained from more specialised laboratory techniques, like genetic studies, to classify AML more precisely. This information also provides more reliable information regarding the likely course (prognosis), of a particular subtype of AML, and the best way to treat it.
Some subtypes of AML are associated with specific symptoms. For example, in some subtypes of AML, leukaemic cells can spread from the bloodstream into other parts of the body like the gums, causing swelling and discomfort in this area. Acute promyelocytic leukaemia (APML or M3) is associated with bleeding and abnormalities in blood clotting. APML is treated differently to other types of AML, and usually has a good overall prognosis.
How common is AML in children?
Less than a quarter of acute leukaemia diagnoses in children are AML. Around 50 children (0-14 years) are diagnosed with AML in Australia each year.
Who gets childhood AML?
AML can affect children of any age, and girls and boys are affected equally. ALL is the more common childhood acute leukaemia and AML is more prevalent in adults than ALL.
Causes of childhood acute myeloid leukaemia (AML)
In most cases the causes of AML remain largely unknown but it is thought to result from damage to one or more of the genes that normally control blood cell development. Research is going on all the time into possible causes of this damage and certain factors have been identified that may put some children at an increased risk. These include:
- siblings of a child diagnosed with AML have a slightly higher risk of being diagnosed with AML themselves. This risk is considered quite small though.
- exposure to very high doses of radiation, although very few people in Australia are exposed to radiation levels high enough to increase their risk of AML
- exposure to industrial chemicals like benzene over a long period and certain types of chemotherapy to treat other cancers
- some congenital disorders are associated with the development of AML, like Down syndrome, Bloom syndrome and Fanconi’s anaemia. In these cases the AML tends to develop in childhood or adolescence. In very rare cases, AML develops because an abnormal gene is passed down from one generation to the next.
- some people with pre-existing blood disorders including certain myelodysplastic syndromes (MDS) and myelofibrosis, aplastic anaemia and paroxysmal nocturnal haemoglobinuria have a higher than average risk of developing AML.
Symptoms of childhood acute myeloid leukaemia (AML)
Because AML develops quickly, children are usually unwell for only a short period of time before they are diagnosed (days or weeks). The most common symptoms of AML are caused by a shortage of normal blood cells in the circulating blood. These symptoms include:
- anaemia – a low haemoglobin level in the blood can cause your child to have symptoms of persistent tiredness and fatigue, pale complexion, weakness, dizziness or feeling unusually short of breath when physically active
- increased bleeding or bruising – a very low platelet count can cause bruising for no apparent reason, or excessive or prolonged bleeding following minor cuts or injury. Some children have frequent or severe nosebleeds or bleeding gums. Red or purple flat pinhead sized spots may appear on the skin, especially on the legs. These are called petechiae (‘pe-teekee- a’) and they are caused by tiny bleeds under the skin.
- frequent or repeated infections – with a low white blood count children are more likely to develop frequent or repeated infections. These may present as minor skin infections, a sore throat, sore mouth or slow healing of minor cuts and grazes. They may also develop chest infections (coughing), urinary tract infections (frequent passing of urine with a sensation of burning) and fevers. The leukaemia itself can cause of low grade fever, in the absence of an infection.
- bone pain – bone and/or joint pain is common and results from the marrow being literally ‘stuffed’ with leukaemic cells. Occasionally there may be deposits of leukemic cells in bone itself and this can cause localised pain.
- other symptoms – other symptoms may include swollen lymph nodes (glands), chest pain and abdominal discomfort due to a swollen spleen or liver.
Some of the symptoms described above may also be seen in other illnesses, including viral infections. So, most children with these symptoms don’t have leukaemia. However, it is important to see your doctor if your child has any unusual symptoms, or symptoms that don’t go away so that they can be examined and treated properly.
Diagnosis of childhood acute myeloid leukaemia (AML)
AML is diagnosed by examining samples of your child’s blood and bone marrow.
Full blood count
The first step in the diagnosis is a simple blood test called a full blood count (FBC) or complete blood count (CBC). This involves a sample of blood from a vein in your child’s arm being sent to the laboratory for investigation. Most children with AML have a low red cell and platelet count.
Many of the white blood cells may be abnormal leukaemic blast cells and the presence of these blast cells suggests you have AML. An AML diagnosis needs to be confirmed by examining the cells in the bone marrow.
Bone marrow examination
If the results of the blood tests suggest AML, a bone marrow biopsy may be required to help confirm the diagnosis. A bone marrow biopsy involves taking a sample of bone marrow (usually from the back of the hip bone) and sending it to the laboratory for examination under the microscope.
The bone marrow biopsy may be done in the clinic or day procedure centre and is usually performed under a light anaesthetic or sedation given through a small drip in your child’s arm. The sample of bone marrow is examined in the laboratory to determine the number and type of cells present and the amount of haematopoiesis (blood-forming) activity taking place there.
An AML diagnosis is confirmed by the presence of an excessive number of blast cells in the bone marrow.
Cerebrospinal fluid examination (lumbar puncture)
A small sample of the cerebo-spinal fluid (CSF) that surrounds your child’s brain and spinal cord is collected under anaesthetic during a procedure called a lumbar puncture, and tested in the laboratory to check for the presence of cancer cells within the central nervous system (CNS).
If cells are found, additional treatment is given to the CNS. The CSF is usually negative but even in this case some CNS-directed treatment (CNS prophylaxis) is required as a very small number of cells may be present but not detectable.
Further Testing
Once the diagnosis of AML is made, blood and bone marrow cells are examined further using special laboratory tests. These include immunophenotyping and cytogenetic tests. These tests provide more information about the exact type of AML your child has, the likely course of the disease and the best way to treat it.
Other tests may be conducted to provide information on your child’s general health and how their vital organs are functioning. These include a combination of further blood tests and imaging tests (x-rays, scans and ECG).
These results will provide a baseline of your child’s disease and general health, which will be compared with later results to assess how well your child is progressing and responding to treatment.
Treatment of childhood acute myeloid leukaemia (AML)
AML usually progresses quite quickly so treatment needs to begin as soon as it is diagnosed. Children diagnosed with AML need to be treated in a specialist paediatric referral centre under the care of a specialist doctor called a paediatric haematologist/oncologist.
The type of protocol your child is allocated to will depend on the ‘risk group’ to which they belong. The risk group to which they belong will be defined based on a number of clinical and laboratory factors, both at diagnosis and during treatment, that predict the outcomes of particular treatment approaches.
Sometimes adjustments need to be made to your child’s protocol depending on how well they are responding to treatment. It is important to realise that whatever protocol your child follows, it is the best treatment known against AML at the time.
Induction Treatment
Chemotherapy is the main form of treatment given for AML. Initially the aim of treatment is to destroy leukaemic cells and induce a remission. This means that there is no evidence of leukaemic cells in the blood and bone marrow and that normal blood cell production and normal blood counts are restored. In remission there is a small chance that some residual cells may still exist and therefore further cycles of treatment are given to reduce the chance of relapse. This is called post-remission or consolidation therapy.
Chemotherapy is usually given as a combination of drugs, which make up different courses of treatment usually given over a period of a week or so. Further courses of chemotherapy are given but are spaced out by three or four weeks. In most cases the drugs are given as infusions through a special line called a central venous catheter, which will be inserted before your child starts treatment. A central venous catheter is a special line inserted through the skin into a large vein in their arm, neck or chest.
Once in place, chemotherapy and other drugs can be given through the line and blood tests can also usually be taken from the line without the need for frequent needle pricks. There are several different kinds of central lines used. Some are intended for short-term use while others can remain in place for months or even years.
At the end of induction treatment a bone marrow test will be undertaken to examine the bone marrow for evidence of leukaemic cells.
Post remission/consolidation treatment
The consolidation protocol chosen for your child will depend on their estimated risk of relapse in the future and their response to their induction treatment. Children are categorised as having low, standard or high-risk AML. This ensures that the most appropriate and effective ‘risk-based’ therapy can be chosen for every child.
The purpose of consolidation is to prevent relapse. If your child is standard or good risk then further cycles of chemotherapy are given to destroy any remaining leukaemic cells. This may be a further two to three cycles of chemotherapy treatment.
For high-risk children, consolidation treatment may be further blocks of chemotherapy treatment or a stem cell transplant from a matched donor.
Bone marrow/stem cell transplant
Transplantation of donor stem cells is a treatment option following chemotherapy for patients whose AML is at high risk for relapse. Stem cell transplant is also a treatment option if your child’s AML relapses post-chemotherapy treatment. Further information on allogeneic (donor) transplants can be found on our transplant page.
Central nervous system treatment and prophylaxis
Leukaemic cells are sometimes found in the central nervous system (CNS – brain and spinal cord) at the time of diagnosis. In other cases AML reappears or relapses within this area at a later stage. Because the blood supply to the CNS is different from the blood supply to other parts of the body, this area can act as a ‘sanctuary site’ or hiding spot for leukaemic cells.
CNS treatment and prophylaxis (protection) will be given at various stages throughout your child’s treatment. This usually involves injections of chemotherapy drugs directly into the spinal fluid (intrathecal injection), through a lumbar puncture. Some types of intravenous chemotherapy and cortico-steroid therapy also provide valuable protection for the CNS.
On rare occasions, radiation therapy to the head (cranial irradiation) is also used.
Relapse
Eighty percent of children with AML will go into remission and 50-60 % of those diagnosed will remain disease-free following their initial remission. Finding out that your child’s leukaemia has relapsed can be devastating, but there are generally a number of options to try that can get the leukaemia under control.
The treatment of relapsed disease depends on a number of factors including the duration of the remission and the site at which the disease has reappeared. Other factors are also considered including your child’s age and the genetic make-up of the relapsed leukaemic cells. Similar drugs to those used to initially treat leukaemia, different drugs, and in some cases high dose chemotherapy and a stem cell transplant may be used to treat relapsed disease. Your child’s treating specialist will discuss all the treating options available to your child.
Side effects of childhood AML treatment
All treatments can cause side effects. However, the type and severity will vary between individuals, depending on the type of treatment used and how an individual responds to it. In general, more intensive treatment is associated with more severe side effects. It is important to report any symptoms your child is having to your doctor or nurse. In most cases they can be treated and are reversible. Information about the specific side effects of your child’s treatment should be discussed with your treating doctor.
When to contact your doctor or hospital
As a general rule, while your child is having treatment you will need to contact your doctor or hospital immediately if they have any of the following:
- a temperature of 38oC or over (even if it returns to normal) and/or an episode of uncontrolled shivering (a rigor)
- bleeding or bruising, for example blood in their urine and/or faeces, sputum, bleeding gums or a persistent nose bleed
- nausea or vomiting that prevents them from eating or drinking or taking their normal medications
- severe diarrhoea, stomach cramps or constipation
- coughing or shortness of breath
- a new rash, reddening of the skin, itching
- a persistent headache
- a new pain or soreness anywhere
- if they cut or otherwise injure themselves
- if you notice pain, swelling, redness or pus anywhere on their body.
What are the side effects of childhood AML treatment?
Side effects of chemotherapy
Chemotherapy kills cells that multiply quickly, such as leukaemic cells. It also causes damage to fast-growing normal cells, including hair cells and cells that make up the tissues in the mouth, gut and bone marrow. The side effects of chemotherapy occur as a result of this damage. These include:
Effects on the bone marrow
Chemotherapy affects the bone marrow’s ability to produce adequate numbers of blood cells. As a result, the blood count (the number of white cells, platelets and red cells circulating in your blood) will generally fall within a week of treatment. The length of time it takes for the bone marrow and blood counts to recover mainly depends on the type of chemotherapy given.
When the platelet count is very low (thrombocytopenic) your child can bruise and bleed more easily. During this time it is helpful to avoid sharp objects in their mouth such as chop bones or potato chips as these can cut their gums. Using a soft toothbrush also helps to protect their gums. In many cases a transfusion of platelets is given to reduce the risk of bleeding until the platelet count recovers.
If the red blood cell count and haemoglobin levels drop they will probably become anaemic. When a child is anaemic they feel more tired and lethargic than usual. If their haemoglobin level is very low, the doctor may prescribe a blood transfusion.
Risk of infection
The point at which the white blood cell count is at its lowest is called the nadir. This is usually expected 10 to 14 days after having chemotherapy. During this time your child will be at a higher risk of developing an infection. At this stage they will also be neutropenic, which means that their neutrophil count is low.
Neutrophils are important white blood cells that help us to fight infection. While their white blood cell count is low you should take sensible precautions to help prevent infection. These include avoiding crowds, avoiding close contact with people with contagious infections (for example colds, flu, chicken pox) and your child only eating food that has been properly prepared and cooked. If your child does develop an infection they may experience a fever, which may or may not be accompanied by an episode of shivering where they shake uncontrollably. Infections while they are neutropenic can be quite serious and need to be treated with antibiotics as soon as possible.
Nausea and vomiting
Nausea and vomiting are often associated with chemotherapy and some forms of radiotherapy. These days however, thanks to significant improvements in anti-sickness (anti-emetic) drugs, nausea and vomiting are generally very well controlled. Your child will be given anti-sickness drugs before and for a few days after their chemotherapy treatment. Be sure to tell the nurses and doctors if the anti-emetics are not working for your child.
Some people find that eating smaller meals more frequently during the day, rather than a few large meals, helps to reduce nausea and vomiting. Many find that eating cool or cold food is more palatable, for example jelly or custard. Drinking ginger ale or soda water and eating dry toast may also help if your child is feeling sick.
Parotitis
Associated with radiotherapy, parotitis is an inflammation of the saliva-producing glands in the mouth, which can occur if these glands are within the treatment field used. These include the parotid or submandibular glands, which are situated at the top of the jaw line, in front of the ears. Parotitis causes dryness of the mouth and jaw pain, which usually settles down within a few days, once the inflammation subsides.
Changes in taste and smell
Both chemotherapy and radiation therapy can cause changes to the sense of taste and smell. This is usually temporary but in some cases it lasts up to several months. There are lots of reasons why children may not feel like eating much during treatment, especially while they are having treatment or are in hospital. Allowing your child to eat when they are hungry, which often means snacking in between meal times, and offering them nutritious snacks and drinks throughout the day can be helpful.
Mucositis
Mucositis, or inflammation of the lining of the mouth, throat or gut is a common and uncomfortable side effect of chemotherapy and some forms of radiotherapy. It usually starts about a week after the treatment has finished and goes away once their blood count recovers, usually a couple of weeks later. During this time the mouth and throat could get quite sore. Soluble pain medication and other topical drugs (ones which can be applied to the sore area) can help.
Always check your child’s temperature before giving them pain medication as this drug can ‘mask’ signs of infection (a raised temperature). If the pain becomes more severe, stronger pain killers might be needed.
It is important to keep your child’s mouth as clean as possible while they are having treatment to help prevent infection. Avoid commercial mouthwashes as these are often too strong or they may contain alcohol, which will hurt their mouth.
Bowel changes
Chemotherapy can cause some damage to the lining of the bowel wall. This can lead to cramping, wind, abdominal swelling and diarrhoea. Be sure to tell the nurses and doctors if your child experiences any of these symptoms.
If they develop diarrhoea, a specimen will be required to ensure that the diarrhoea is not the result of an infection. After this they will be given some medication to help stop the diarrhoea and/or the discomfort. It is also important to tell the nurse or doctor if they are constipated or feeling any discomfort or tenderness around their anus while they are trying to move their bowels. They may need a gentle laxative to help soften their bowel motion.
Hair loss
Hair loss is unfortunately a very common side effect of chemotherapy and some forms of radiotherapy. However, it is usually only temporary. The hair starts to fall out within a couple of weeks of treatment and tends to grow back three to six months later.
Avoiding the use of heat or chemicals and only using a soft hairbrush and a mild baby shampoo can help reduce the itchiness and scalp tenderness which can occur while your child is losing their hair. The child will need to avoid direct sunlight on their exposed head (get them to wear a hat) because chemotherapy and radiotherapy makes their skin even more vulnerable to the damaging effects of the sun (like sunburn and skin cancers). Remember that without hair their head can get quite cold so a beanie might be useful.
Hair can also be lost from their eyebrows, eyelashes, arms and legs. Many young children are not worried by losing their hair and are happy to wear hats, scarves or bandanas. However, older children and teenagers are often more concerned about the effects of hair loss and other changes to their appearance. Having a wig may give them the confidence to participate in everyday activities, particularly those involving friends.
Fatigue
Most children experience some degree of tiredness in the days and weeks following chemotherapy and radiotherapy. Getting plenty of rest and a little light exercise each day may help to make your child feel better during this time. It is important for them to rest when they are tired.
Fertility
Most children who are treated for AML will grow up and be able to have normal, healthy babies. For others, treatment may cause a reduction in their fertility and their ability to have children in the future. This may depend on the age of the child when they were treated and the type of treatment they received.
In boys, sperm production may be impaired for a while following chemotherapy but it is important to realise that the production of new sperm may become normal again in the future.
In girls, chemotherapy and radiotherapy can cause varying degrees of damage to the normal functioning of the ovaries. This will depend on the age of the child and the dose of radiotherapy or chemotherapy given. In some cases this leads to menopause earlier than expected. The onset of puberty can also be affected and some children may require hormonal supplements to ensure normal sexual development.
Body image, sexuality and sexual activity
Hair loss, skin changes and fatigue can all interfere with how your child feels about and sees themselves. If you have older children who are sexually active, it is usually recommended that they do not become pregnant as some of the treatments given might harm the developing baby; therefore a suitable form of contraception needs to be used.
Seizures
Intrathecal (IT) therapy is rarely associated with seizures, otherwise known as fitting. If your child experiences a seizure, or if the doctor feels they may be at risk of having a seizure, they will prescribe special medication to help to prevent this from happening.
Side effects of cortico-steroids
Side effects of cortico-steroids depend largely on how long they are used for, and the dose given. Again, some children respond differently. An increased appetite, fluid retention and weight gain and the classic ‘moon-shaped’ face and swollen belly are common side effects of these drugs.
Some children find it more difficult to get to sleep at night and to stay asleep, and some night sedation may be required. Mood swings, anxiety, restlessness and nightmares are also common side effects of steroid therapy.
A child’s moods and behaviours can be challenging while they are receiving steroids. While accepting that some allowances need to be made, maintaining your normal parenting strategies is important during this time. Being consistent and setting limits on your child’s behaviour can help to make them feel more secure. It can also help to prevent unpleasant longer-term behavioural problems, which can cause considerable stress within any family.
Long-term use of steroid therapy may cause other effects such as fluid retention, an increased susceptibility to infections, or osteoporosis, where the bones may become weak and brittle. However these effects are not common, as most children with AML do not require prolonged steroid therapy.
Caring for someone with childhood acute myeloid leukaemia (AML)
We have a range of information and resources that may help when you are caring for someone with childhood acute myeloid leukaemia (AML).
