What is acute lymphoblastic leukaemia?
Leukaemia is cancer of the white blood cells. Acute leukaemia means the condition progresses rapidly and aggressively and requires immediate treatment.
Acute leukaemia is classified according to the type of white blood cells that are affected by cancer. There are two main types:
- lymphocytes, which are mostly used to fight viral infections
- neutrophils, which perform several functions, such as fighting bacterial infections, defending the body against parasites and preventing the spread of tissue damage
These pages focus on acute lymphoblastic leukaemia, which is cancer of the lymphocytes. The following other types of leukaemia are covered elsewhere:
Warning signs of acute leukaemia
Symptoms of acute lymphoblastic leukaemia usually begin slowly before rapidly getting severe as the number of immature white blood cells in your blood increases (see below for an explanation of this). Symptoms include:
- pale skin
- having repeated infections over a short space of time
- unusual and frequent bleeding
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What happens in acute leukaemia
All of the blood cells in the body are produced by bone marrow. Bone marrow is a spongy material found inside the bones. It is important because it produces special cells called stem cells.
Stem cells are very useful because they have the ability to create other specialised cells that carry out important functions. The stem cells in bone marrow produce three important types of blood cells:
- red blood cells, which carry oxygen around the body
- white blood cells, which help fight infection
- platelets, which help stop bleeding
Usually the bone marrow produces stem cells which are allowed to mature into "adult" blood cells. However, in cases of acute leukaemia, the affected bone marrow begins to release a large number of immature white blood cells that are known as blast cells.
The immature white blood cells begin to rapidly disrupt the normal balance of cells in the blood. This means that the body does not have enough red blood cells or platelet cells. This can cause symptoms of anaemia, such as tiredness, and increase the risk of excessive bleeding.
Also, as the white blood cells are not properly formed they become less effective at fighting bacteria and viruses, making you more vulnerable to infection.
If you have acute leukaemia that is left untreated, you will not be able to survive because your blood supply will not function properly.
How common is acute lymphoblastic leukaemia?
Acute leukaemia is an uncommon type of cancer. About 7,600 people are diagnosed with leukaemia each year in the UK. Of these, only about 650 people have acute lymphoblastic leukaemia.
Despite being uncommon overall, acute lymphoblastic leukaemia is the most common type of cancer to affect children. Approximately 1 in every 2,000 children will develop it. About 85% of cases occur in children aged under 15, with the majority of cases developing in those between the ages of two and five years old.
The cause or causes of acute leukaemia are uncertain, but known risk factors include:
- exposure to high levels of radiation
- exposure to benzene, a chemical used in manufacturing that is also found in cigarettes
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The outlook for children with acute lymphoblastic leukaemia is usually good. Almost all children will achieve a remission (a period of time where they are free from symptoms) from their symptoms, and 85% will be completely cured.
The outlook for adults with acute lymphoblastic leukaemia is less promising as only 40% of people with the condition will be completely cured.
Treatments for acute lymphoblastic leukaemia usually involve a combination of chemotherapy and radiotherapy. In some cases, amay also be needed to achieve a cure.
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If a cure is not possible, there is a risk that the lack of healthy blood cells can make the person extremely vulnerable to life-threatening infections (due to the lack of white blood cells) or uncontrolled and serious bleeding (due to the lack of platelets).
Acute lymphoblastic leukaemia symptoms
Symptoms of acute lymphoblastic leukaemia usually begin slowly before rapidly getting severe as the number of blast cells (immature white blood cells) in your blood increases.
Most of the symptoms are caused by the lack of healthy blood cells in your blood supply.
Symptoms of acute lymphoblastic leukaemia include:
- pale skin
- having repeated infections over a short space of time
- unusual and frequent bleeding, such as bleeding gums or nose bleeds
- high temperature (fever) of 38C (100.4F) or above
- excessive sweating
- bone and joint pain
- easily bruised skin
- swollen lymph nodes (glands)
- swollen liver
- swollen spleen
- weight loss
In some cases of acute lymphoblastic leukaemia, the affected cells can spread from your bloodstream into your central nervous system. This can cause a series of neurological symptoms (related to the brain and nervous system) including:
- seizures (fits)
- blurred vision
When to seek medical advice
If you or your child has some or even all of the symptoms listed above, it is still highly unlikely that acute leukaemia is the cause.
However, see your doctor as soon as possible because any condition that causes these symptoms needs to be promptly investigated and treated.
Acute lymphoblastic leukaemia causes
Acute lymphoblastic leukaemia begins with an alteration to the structure of DNA found in the stem cells responsible for producing white blood cells. This is known as a genetic mutation.
The DNA provides the cells with a basic set of instructions, such as when to grow and reproduce. The mutation in the DNA changes these instructions so that stem cells produce more white blood cells than are needed.
The white blood cells are also produced when they are still immature, so they do not have the infection-fighting properties of healthy "adult" white blood cells.
The number of immature cells (blast cells) increases rapidly, leading to a corresponding decrease in red blood cells and platelets. This reduction in other types of healthy blood cells causes many of the symptoms of acute leukaemia.
It is not known what triggers the condition's development and causes the initial mutation to occur in the stem cells. Most experts believe that the likely triggers of childhood acute leukaemia differ from those of adult acute leukaemia.
Possible triggers of childhood leukaemia
It is thought that around 5% of childhood acute lymphoblastic leukaemia cases are caused by related genetic disorders. For example, rates of leukaemia tend to be higher in children with Down’s syndrome.
Exposure to radiation, either before birth or afterwards, is a known risk factor. However, it would require a significant level of radiation, such as the amount released during the nuclear reactor accident at Chernobyl. Due to the potential risk of radiation to unborn babies, medical techniques and equipment that use radiation, such as, are rarely used on pregnant women.
Most cases of childhood leukaemia occur in children with no history of genetic disorders or exposure to radiation.
The two-hit theory
Most experts support what is sometimes referred to as the "two-hit" theory of childhood leukaemia.
The "two-hit" theory argues that a small number of children are born with a pre-existing vulnerability to developing acute leukaemia, such as a genetic mutation.
However, the theory suggests that they will remain healthy unless they are exposed to a second environmental trigger (hit) and it is this that is required for the condition to develop. Many researchers believe that the second trigger is linked to an infection during childhood.
The possible role of infection
One theory argues that children who have a pre-existing vulnerability to developing acute leukaemia, and who are not exposed to infection at an early age, may develop an immature immune system. When their immune system finally meets an infection, it somehow malfunctions and causes a mutation in the stem cells to occur.
The evidence to support this theory is that children who attend playgroups at an early age are less likely to develop acute leukaemia compared with those who do not attend playgroups when they are very young.
Children who mix with others from an early age are exposed to common childhood infections that activate and strengthen their immune systems, making them more resilient to any subsequent infections.
An alternative theory is that leukaemia may be the result of an increase in the mixing of different populations. For example, when people move from different parts of the country and go to live in a new town.
This may expose children with the pre-existing vulnerability to developing acute leukaemia to infections that their immune system has not learnt to recognise or deal with. This may trigger a similar malfunction and cause a mutation in the stem cells.
The evidence for this is that clusters of leukaemia cases have been recorded near large-scale building projects where families from across the UK are congregated in one place.
However, these theories are not suggesting that leukaemia is infectious, but that it is caused by a rare reaction to infection.
Possible environmental factors
Experts have also carried out extensive research in order to determine whether the following environmental factors could be a trigger for leukaemia:
- living near a nuclear power station
- living near a power line
- living near a building or facility that releases electro-magnetic radiation, such as a mobile phone mast
At the moment there is no evidence to confirm that any of these environmental factors increases the risk of developing leukaemia.
Possible triggers for adult acute leukaemia
Exposure to the chemical benzene is a known risk factor for adult acute leukaemia. Benzene is found in petrol and is also used in the rubber industry. However, there are strict controls to protect people from prolonged exposure.
Benzene is also found in cigarettes, which could explain why smokers are three times more likely to develop acute leukaemia than non-smokers. People who have hadand to treat earlier, unrelated cancers also have an increased risk of developing acute leukaemia.
As with childhood acute leukaemia, exposure to high levels of radiation is also a risk factor. People who spend long periods of time in aeroplanes may also be more at risk because the high altitude provides less protection against the sun’s radiation. However, the risk is only thought to be significant if you have spent at least 5,000 hours flying.
Diagnosing acute lymphoblastic leukaemia
When first diagnosing acute leukaemia, your doctor will check for physical signs of the condition, such as swollen glands, and will arrange for you to have blood tests.
A high number of abnormal white blood cells in the test sample could indicate the presence of acute leukaemia. If your blood test indicates abnormal results, you will be referred to a haematologist (a specialist in treating blood conditions).
Bone marrow biopsy
To confirm a diagnosis of acute leukaemia, the haematologist will take a small sample of your bone marrow to examine under a microscope. This procedure is known as a bone marrow biopsy. A bone marrow biopsy is usually carried out under a.
The haematologist will numb an area of skin at the back of your hip bone before using a needle to remove a sample of bone marrow. The procedure is usually painless, although you may experience some bruising and discomfort for a few days afterwards. The procedure takes around 15 minutes to complete and you should not have to stay in hospital overnight.
The bone marrow sample will be checked for any cancerous cells. If cancerous cells are present, the biopsy will also be able to determine which type of acute leukaemia is present.
There are various additional tests that can be used to help reveal more information about the progress and extent of the leukaemia. They can also provide an insight into how the leukaemia should be treated. These tests are described below.
Cytogenetic testing involves identifying the genetic make-up of the cancerous cells. There are specific genetic variations that can occur during leukaemia, and knowing what these variations are can have an important impact on treatment.
Lymph node biopsy
If you have been diagnosed with acute leukaemia, further biopsies may be carried out on any enlarged lymph nodes that you have. These will be able to establish how far the leukaemia has spread.
If you have acute leukaemia, a computerised tomography scan () may be used to check that your organs, such as your heart and lungs, are healthy.
If it is felt that there is a risk that acute leukaemia has spread to your nervous system, amay be carried out.
A lumbar puncture is a test where a needle is used to extract a sample of cerebrospinal fluid (fluid that surrounds and protects your spine) from your back. The fluid is tested to determine whether leukaemia has reached your nervous system.
Acute lymphoblastic leukaemia treatment
As acute leukaemia is an aggressive condition that develops rapidly, treatment will usually begin a few days after a diagnosis has been made.
Because of the often complex nature of acute leukaemia, the condition is usually treated by a team of different specialists working together. This type of team is known as a multidisciplinary team (see box, left).
Stages of treatment
Treatment for acute lymphoblastic leukaemia is carried out in stages:
- Induction – the aim of the initial stage of treatment is to kill the leukaemia cells in your bone marrow, restore your blood to proper working order and resolve any symptoms that you may have.
- Consolidation – this stage aims to kill any remaining leukaemia cells that may be present in your central nervous system.
- Maintenance – the final stage involves taking regular doses of chemotherapy tablets to prevent the leukaemia returning.
Maintenance only seems to be effective in treating acute lymphoblastic leukaemia; it is not usually used in the treatment of acute myeloid leukaemia.
The induction stage of treatment is carried out in hospital or in a specialist centre. This is because you will probably need to have regular blood transfusions as it is likely that your blood will not contain enough healthy blood cells.
You will also be vulnerable to infection, so it is important that you are in a sterile environment where your health can be carefully monitored and any infection that you have can be promptly treated. You may also be prescribed antibiotics to help prevent further infection.
You will be given a combination ofmedication to kill the leukaemia cells in your bone marrow. As you will need to have many medicines as part of your treatment, a tube will be inserted into a large vein near your heart. This is known as a central line. Having a central line means that you will not need to have many painful injections.
Some chemotherapy medication may also be directly administered into your cerebrospinal fluid to kill any leukaemia cells that may have spread to your nervous system. This is given using a needle that is placed into your spine, in a similar way to a.
Side effects that occur following chemotherapy are common. They can include:
- loss of appetite
- mouth ulcers
- skin rashes
- hair loss
The side effects should resolve once treatment has finished. Your hair will usually take between three to six months to grow back.
If you have the type known as Philadelphia chromosome positive acute lymphoblastic leukaemia, you will also be given a medicine called imatinib. Imatinib works by blocking the signals in the cancerous cells that cause them to grow and reproduce. This kills the cancerous cells.
Imatinib is taken orally (as a tablet). The side effects of imatinib are usually mild and should improve over time. They include:
- swelling in the face and lower legs
- muscle cramps
Depending on how well you respond to treatment, the induction phase can last from two weeks to several months. In some cases, you or your child may be able to leave hospital and receive treatment on an outpatient basis if your symptoms improve.
Leukaemia can return if just one cancerous cell remains in your body. Therefore the aim of consolidation treatment is to ensure that any remaining leukaemia cells are killed.
Treatment involves receiving regular injections of chemotherapy medication. This is usually done on an outpatient basis, which means that you will not have to stay in hospital overnight. However, you may require some short stays in hospital if your symptoms suddenly get worse or if you develop an infection.
The consolidation phase of treatment lasts several months.
The maintenance phase is designed to act as further insurance against the possibility of the leukaemia returning. It involves taking regular doses of chemotherapy tablets while undergoing regular check-ups to monitor how effective your treatment is proving.
The maintenance phase can often last for two years.
As well as chemotherapy and imatinib, other treatments are used in some circumstances. These are described below.
Dasatinib is a new type of medication used to treat Philadelphia chromosome-positive acute lymphoblastic leukaemia, when all other treatments have proved unsuccessful.
Dasatinib is a tyrosine kinase inhibitor. This means it blocks a protein called tyrosine kinase that helps stimulate the growth of cancer cells.
Dasatinib cannot cure acute leukaemia but it can slow its growth, helping to relieve symptoms and prolong lifespan.
Radiotherapyinvolves using high doses of controlled radiation to kill cancerous cells. There are two main reasons why radiotherapy is usually used to treat acute leukaemia:
- to sometimes treat advanced cases of acute lymphoblastic leukaemia that have spread to the nervous system or brain
- to prepare the body for a bone marrow transplant (see below)
Side effects of both types of radiotherapy include:
- hair loss
The side effects should pass once your course of radiotherapy has been completed. However, your skin may be very sensitive to the effects of light for several months after the treatment has finished. If this is the case, avoid sunbathing or exposure to sources of artificial light, such as sunbeds, for several months.
Many younger children treated with radiotherapy will go on to have restricted physical growth during puberty.
A small number of people develop cataracts several years after radiotherapy. Cataracts are cloudy patches in the lens (the transparent structure at the front of the eye) that can make your vision blurred or misty. Cataracts can usually be successfully treated using surgery.
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Bone marrow and stem cell transplants
If you or your child do not respond to chemotherapy, a possible alternative treatment option is bone marrow or stem cell transplantation.
Before transplantation can take place, the person receiving the transplant will need to have aggressive high-dose chemotherapy and radiotherapy to destroy any cancerous cells in their body. This can put an enormous strain on the body and cause significant side effects and potential complications.
Transplantations have better outcomes if the donor has the same tissue type as the person who is receiving the donation. The best candidate to provide a donation is usually a brother or sister with the same tissue type.
Due to these issues, transplantations are usually only successful when they are carried out in children and young people, or older people who are in good health, and when there is a suitable donor, such as a brother or sister.
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Complications of acute lymphoblastic leukaemia
Having a weakened immune system is a common complication of acute leukaemia. The medical term for having a weakened immune system is being "immunocompromised".
Even if your blood is restored to normal working order, many of the medications that are used to treat acute leukaemia have the side effect of weakening your immune system.
This means that you are more vulnerable to developing an infection, and that any infection you have has an increased potential to cause serious complications. You may be advised to take regular doses of antibiotics to prevent infections.
Avoid contact with anyone who is known to have an infection even if it is a type of infection that you were previously immune to, such as chickenpox or measles. This is because your previous immunity to these conditions may be suppressed.
While it is important to go outside on a regular basis, both for exercise and for your psychological wellbeing, avoid visiting crowded places and using public transport during rush hour.
Report any possible symptoms of an infection immediately to your doctor or care team because prompt treatment may be required to prevent serious complications.
Symptoms of infection include:
- high temperature (fever) of 38C (100.4F) or above
- aching muscles
Also ensure that all of your vaccinations are up-to-date. Your doctor will be able to advise you about this.
However, you will not be able to have any vaccine that contains activated particles of viruses of bacteria, such as:
- the mumps, measles and rubella (MMR) vaccine
- the polio vaccine
- the oral typhoid vaccine
- the BCG vaccine (used to vaccinate against tuberculosis)
- the yellow fever vaccine
If you have acute leukaemia, you will bleed and bruise more easily due to the low levels of platelets (clot-forming cells) in your blood. Bleeding may also be excessive when it does occur.
Bleeding can occur:
- inside the skull (intracranial haemorrhage)
- inside the lungs (pulmonary haemorrhage)
- inside the stomach (gastrointestinal haemorrhage)
The symptoms of an intracranial haemorrhage include:
- severe headache
- stiff neck
- change in mental state, such as confusion
The most common symptoms of a pulmonary haemorrhage are:
- coughing up blood from your nose and mouth
- breathing difficulties
- a bluish skin tone (cyanosis)
The two most common symptoms of a gastrointestinal haemorrhage are:
- vomiting blood
- passing stools (faeces) that are very dark or tar-like
All three types of haemorrhages should be regarded as medical emergencies. Call for an ambulance if you suspect that you or your child is experiencing a haemorrhage.
Many of the treatments that are used to treat acute leukaemia can cause infertility. Infertility is often temporary, although in some cases it may be permanent.
People who are particularly at risk of becoming infertile are those who have received high doses of chemotherapy and radiotherapy in preparation for bone marrow or stem cell transplantation.
Your multidisciplinary team will be able to provide you with a good estimation regarding the risk of infertility in your specific circumstances.
It may be possible to guard against any risk of infertility before you begin your treatment. For example, men can have samples of their sperm stored. Similarly, women can have fertilised embryos stored, which can then be placed back into their womb following treatment.
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