Childhood acute lymphoblastic leukaemia (ALL)

About childhood acute lymphoblastic leukaemia (ALL)

Excess numbers of these abnormal lymphocytes, known as lymphoblasts, leukaemic blasts or leukaemic cells, spill out of the bone marrow and circulate around the body in your child’s blood stream.

Improvements in the diagnosis and treatment of children with ALL mean that, these days, almost all children treated for ALL will achieve a remission from their disease and most will be cured.

How common is ALL in children?

Acute lymphoblastic leukaemia represents 55% of all blood cancer diagnoses in children aged 0-14 years.

Who gets childhood ALL?

The incidence of ALL is highest in children between the ages of two and four. It is more commonly diagnosed in boys.

Causes of childhood acute lymphoblastic leukaemia (ALL)

No one knows exactly what causes ALL, but it is likely that there are a number of factors, rather than any single factor involved. Research is going on all the time into possible causes and a number of environmental factors continue to be investigated. To date however, none have been proven to cause ALL in children. There are certain factors that may put some children at a higher risk of genetic damage and therefore the development of ALL. These are called risk factors and include:

• genetic factors – genetic factors may play a role in its development. Children with certain congenital disorders like Down syndrome and Fanconi anaemia are at an increased risk of developing ALL.
• infections – there is some evidence to suggest that viral infections may play a role in the development of ALL in some children. It is thought that delayed exposure to common childhood infections or an abnormal response by the child’s immune system to these infections may be involved. This is supported by the higher incidence of ALL reported in particular geographic or demographic areas. ALL is not contagious.
• ionising radiation – children exposed to large doses of ionising radiation (a type of energy emitted from x-rays and radioactive materials) before they were born or in the early years of life may be more at risk. It is unlikely that any children born in Australia are exposed to high enough levels of ionising radiation to cause childhood ALL.
• chemicals – exposure to high levels of benzene and other industrial solvents over a long period of time may increase the risk. Children in Australia are unlikely to be exposed to high enough levels of these chemicals to cause ALL.
• electro-magnetic radiation – in recent years there has been a great deal of controversy about the health effects of living very close to high-voltage power lines and other sources of electro-magnetic radiation such as mobile phones, mobile phone base towers and electrical equipment in our homes. The results of several large international studies have shown, however, that there is no clear evidence to support a link between childhood ALL and exposure to acceptable levels of electro-magnetic radiation in our environment.

Symptoms of childhood acute lymphoblastic leukaemia (ALL)

Because ALL 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 ALL 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 symptoms including lack of energy; persistent tiredness and fatigue; pale complexion; weakness; dizziness; or 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 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 a 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 – these 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. Therefore, 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 lymphoblastic leukaemia (ALL)

ALL is diagnosed by examining samples of your 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 arm being sent to the laboratory for investigation. Most people with ALL have a low red cell and platelet count.

Many of the white blood cells may be abnormal leukaemic blast cells. The presence of these blast cells suggests you have ALL. An ALL diagnosis needs to be confirmed by examining the cells in the bone marrow.

Bone marrow examination

If the results of the blood tests suggest ALL, 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 haematologist’s rooms, clinic or day procedure centre and is usually performed under local anaesthesia with sedation given either by tablet or 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 haemopoiesis (blood forming) activity taking place there.

The diagnosis of ALL is confirmed by the presence of an excessive number of blast cells in the bone marrow.

Cerebrospinal fluid examination

A small sample of the cerebo-spinal fluid (CSF) that surrounds your child’s brain and spinal cord is collected 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 ALL 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 disease 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 such as 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 lymphoblastic leukaemia (ALL)

ALL usually progresses quite quickly so treatment needs to begin as soon as it is diagnosed. Children diagnosed with ALL 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 treatment protocol your child receives will depend on the ‘risk group’ they belong to. 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 ALL at this time.

What are the treatment phases for childhood ALL?

Treatment for ALL can be divided into three phases:

• remission induction therapy
• consolidation therapy (intensification)
• maintenance therapy.

Depending on the protocol your child is following, remission induction, consolidation, interim maintenance and intensification phases of treatment can last for up to 10 months.

Chemotherapy

Many chemotherapy drugs are also called cytotoxics (cell toxic) because they kill cells, especially ones that multiply quickly like cancer cells.

Chemotherapy is the main form of treatment given for ALL. The dose, timing and types of the drugs used will vary depending on the particular disease involved, your child’s age and general health, and the treatment protocol they are following. Chemotherapy is usually given as a combination of drugs (combination chemotherapy). These drugs act together and in different ways to destroy the leukaemic cells. Chemotherapy is usually given in several cycles (or courses) with rest periods in between. This is to allow your child’s body (the bone marrow in particular) time to recover from the side effects.

Some drugs are given in tablet or liquid form (orally), while others may be injected into a vein (intravenously or IV), into a muscle (intramuscularly or IM), and under the skin (subcutaneously or SC). Chemotherapy is also given intrathecally (into the spinal fluid) through a lumbar puncture, to either treat or prevent the spread of leukaemic cells into the central nervous system (CNS – the brain and spinal cord).

Intravenous drugs are usually given through a special line called a central venous catheter (central line or portacath). After their initial treatment your child may be able to receive a majority of their remaining treatment in the outpatient’s department of the hospital or clinic, or at home.

Cortico-steroid therapy

These drugs play an important role in the management of leukaemia. These drugs work by directly killing leukaemic cells as well as enhancing the effects of chemotherapy.

Central nervous system treatment and prophylaxis

Leukaemic cells are sometimes found in the central nervous system (brain and spinal cord) at the time of diagnosis. In other cases ALL 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 under anaesthetic. 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.

Testicular radiotherapy

The testes in boys can also act as a ‘sanctuary site’ for leukaemic cells. However, unless disease is found here at diagnosis no additional treatment is required. Your child’s haematologist/oncologist will decide on the most appropriate treatment in the event of testicular disease. This may or may not include radiotherapy. High dose chemotherapy may also be used.

Remission induction therapy

The goal of remission induction therapy is to destroy any detectable leukaemic cells in your child’s blood and bone marrow and allow their bone marrow to function normally again. Your child will need to be admitted to hospital for this first phase of treatment. Commonly used drugs in this phase of treatment include cortico-steroids, a combination of chemotherapy drugs and intrathecal chemotherapy .

Almost all children with ALL will achieve a remission following induction therapy. In a small number of cases however, the disease does not respond to treatment as expected and the child may be said to have resistant or refractory disease. In these cases the doctor may recommend a more intensive form of therapy to treat your child’s disease more effectively.

Consolidation therapy

Soon after remission induction therapy finishes, consolidation therapy treatment is required to help destroy any leukaemia cells that may be left. This is important because it helps to prevent the disease from re-appearing (relapsing) or spreading to the central nervous system in the future. The consolidation protocol chosen for your child will depend on their estimated risk of relapse in the future. While the outlook for most children with ALL is very good, certain factors (known as prognostic factors) give some children a better chance of being cured of their disease with treatment than others.

The most important of these factors is how well your child’s disease responds to initial treatment, or in other words, how quickly they achieve a remission and how much disease is left over in their body after this initial treatment.

Children are categorised as having low, standard or high-risk ALL. This ensures that the most appropriate and effective ‘risk-based’ therapy can be chosen for every child. Children with high-risk disease can have as good a chance of being cured as those with lower-risk disease when they receive appropriate treatment.

Consolidation therapy usually involves ‘blocks’ of intensification treatment over several months and includes the use of additional chemotherapy drugs. This is given to reduce left over disease to a minimum (minimum residual disease).

Maintenance therapy

Maintenance therapy is designed to help keep your child’s disease in remission and prevent it from reappearing (relapsing) in the future. Common maintenance protocols involve chemotherapy tablets taken daily as well as in some protocols, injections of chemotherapy with courses of cortico-steroids given monthly. In addition, intrathecal injections of chemotherapy may be given periodically to prevent disease relapsing in the central nervous system. This phase of treatment will continue until the treatment is completed.

Currently, the total treatment time for children with ALL is just over two years for girls and just over three years for boys. During this time your child will be treated as an outpatient providing they are well. Your doctor will advise you when it is safe for your child to return to normal daily activities like school, and when it is safe to continue immunisations, which are usually delayed for six to nine months after your child has finished treatment.

While your child is receiving maintenance therapy the doctor will make an assessment of how well your child is progressing and adjust their treatment as necessary.

For a small number of children, the chance of curing ALL with chemotherapy alone may be low. If these children have a sibling with a similar tissue type, or if a suitable unrelated donor can be found on the international registries, the doctors may recommend chemotherapy followed by a haematopoietic stem cell transplant. This uses very high doses of chemotherapy and/or radiotherapy as part of the stem cell transplant procedure.

Due to the complex side effects associated with this form of treatment and the success of current chemotherapy protocols used to treat ALL, a transplant is usually only necessary in selected cases where it has been shown to give a better chance of cure than chemotherapy alone. An example of this might be in the case of very high-risk disease, relapsed disease, or disease which is proving resistant to conventional treatment.

Relapse

Finding out that your child’s leukaemia has relapsed can be devastating, but there are often ways of getting it back 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 makeup 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. Late relapse (relapse that occurs years later) will often respond well to another course of chemotherapy whereas early relapse is generally best treated using stem cell transplantation.

Side effects of childhood ALL treatment

All treatments can cause side effects. The type and severity however 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 to the 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 38^oC 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, 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.

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. The side effects of treatment can 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 depends largely 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 infections that are contagious (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.

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. Solublepain 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, 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. It is, however, 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 (wear a hat) because chemotherapy (and radiotherapy) makes their skin even more vulnerable to the damaging effects of the sun (i.e. sunburn and skin cancers). Remember that without hair your 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. Older children and teenagers however, are often more concerned about the effects of hair loss and other changes to their appearance. Girls are often encouraged to get a wig, whilst they may never wear it, having the 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. Having 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 ALL 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 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 themself. In 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 and therefore a suitable form of contraception is used.

Seizures

Intrathecal (IT) therapy is rarely associated with seizures, otherwiseknown as fitting. If your child experiences a seizure, or if the doctorfeels they may be at risk of having a seizure, they will prescribespecial 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, 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 tostay asleep and some night sedation may be required. Mood swings,anxiety, restlessness and nightmares are also common side effects ofsteroid therapy.

A child’s moods and behaviours can be challengingwhile they are receiving steroids. While accepting that someallowances need to be made, maintaining your normal parentingstrategies is important during this time. Being consistent and settinglimits on your child’s behaviour can help to make them feel moresecure. It can also help to prevent unpleasant longer-term behaviouralproblems, 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. These effects are not common however as most children with ALL do not require prolonged steroid therapy.

Caring for someone with childhood acute lymphoblastic leukaemia (ALL)

We have a range of information and resources that may help when you are caring for someone with childhood acute lymphoblastic leukaemia (ALL).