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Acute lymphoblastic leukaemia

Overview

Leukaemia is a cancer of the bone marrow and white blood cells. There are two types of leukaemia:

  • Acute, where the leukaemia progresses rapidly and aggressively and needs immediate treatment.
  • Chronic, where the leukaemia progresses slowly, over the course of many years. Whether you require immediate treatment for chronic leukaemia will depend on the type of leukaemia that you have.

This article focuses on acute leukaemia.

Bone marrow

All the blood cells in your body are produced in your bone marrow. Bone marrow is a spongy material inside the bones. It is important because it produces special cells known as 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.

Normally, your bone marrow will produce stem cells and these then mature into 'adult' blood cells. With acute leukaemia, the affected bone marrow begins to release a large number of immature white blood cells known as blast cells.

These immature white blood cells begin to disrupt the normal balance of cells in the blood. This means the body does not have enough red blood cells or platelet cells. This can cause symptoms of anaemia, such as tiredness, and lead to excessive bleeding.

Because the white blood cells aren't properly formed they're less effective at fighting bacteria and viruses, making the body more vulnerable to infection.

If you have acute leukaemia and the condition is not treated, you will not be able to survive because your blood supply will not function properly.

White blood cells

There are two types of white blood cell:

  • Lymphocytes, which are mostly used to fight viral infections.
  • Myeloid cells, which have a number of different functions, including fighting bacterial infections, defending the body against parasites and preventing the spread of tissue damage.


Types of acute leukaemia

There are two main types of acute leukaemia:

  • Acute myeloid leukaemia (AML),  which is a cancer of the myeloid cells.
  • Acute lymphoblastic leukaemia (ALL), which is a cancer of the lymphocytes.

How common is acute leukaemia?

Acute myeloid leukaemia (AML) is more common in older people, with most cases occurring in people who are 50 or over. For reasons that are not understood, acute leukaemia is more common in boys and men than in girls and women.

Treating acute leukaemia

Despite being more aggressive than chronic leukaemia, acute leukaemia is easier to treat. Treatment involves chemotherapy and several other medications. More severe cases may require a bone marrow or stem cell transplant.

Prognosis

The outlook for children with ALL is usually good. Almost all children will achieve a remission from symptoms and 80% of them will be completely cured. The outlook for adults with ALL is less promising: only 40% of cases will be completely cured.

The outlook for people with AML varies because there are a number of sub-types of AML, some of which are more challenging to treat than others. Some types of AML have a 75% cure rate, and others only have a 20% cure rate. Younger people with the condition tend to have a better outcome than older people

Causes

Genetic mutation

Acute leukaemia begins with an alteration to the structure of DNA that is 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, or blast cells, then increases rapidly, leading to a corresponding decrease in red blood and platelets. This reduction in the other healthy blood cells is an underlying cause for many of the symptoms of acute leukaemia.

What triggers the development of acute leukaemia and causes the initial mutation in stem cells is unknown. 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 leukaemia cases are caused by related genetic disorders. For example, rates of leukaemia are higher in children with Down's syndrome.

Exposure to radiation, either before, or after birth, is a known risk factor. However, this would require a significant level of radiation, such as that 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 X-rays, are rarely used on pregnant women.

Infection theory

There are two related theories that suggest that acute childhood leukaemia may be triggered by a response to infection.

The first theory states that children who are not exposed to infection at an early age may develop an immature immune system. In a very few of these children, when the immune system does finally meet an infection, it somehow malfunctions and causes a mutation in the stem cells to occur.

The infection theory was developed after it was found that children who attend playgroups at an early age are less likely to develop acute leukaemia compared with children who do not attend playgroups from any early age.

Children who mix with others from an early age are exposed to common childhood infections, which activate their immune system, strengthening it and making it more resilient to subsequent infections.

The second theory states that leukaemia may be the result of a rapid mixing of different populations - for example people coming from different parts of the country to live in a new town. This may expose children to infections that their immune system has not learnt to recognise or deal with and, in a small number of children, it may trigger a similar malfunction and cause a mutation in the stem cells.

Possible environmental factors

Experts have also carried out extensive research in order to see if the following environmental factors could be a trigger for leukaemia:

  • living near to a nuclear power station,
  • living near to a power line, and
  • living near to a building, or facility, that releases electro-magnetic radiation, such as a mobile phone mast.

There is no evidence 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 it is also used in the rubber industry, but there are strict controls that should protect people from prolonged exposure.

However, 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 received chemotherapy and radiotherapy for 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. Also, people who spend prolonged periods of time in aeroplanes may also be more at risk of developing acute leukaemia because the higher 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.

Diagnosis

Blood tests

 

In the initial stages of diagnosing acute leukaemia, your GP will check for physical signs of the condition, such as swollen glands, and arrange for you to have your blood tested.

A high number of abnormal white blood cells in the test sample could indicate the presence of acute leukaemia.

If your blood test does reveal abnormal results, you will be referred to a haematologist (a doctor who specialises in treating blood conditions) for further testing.

 

Bone marrow biopsy

 

In order 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 local anaesthetic.

The haematologist will numb an area of skin at the back of your hip bone, before using a needle to remove the bone marrow sample. 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 the presence of cancerous cells. If cancerous cells are present, the biopsy will also be able to determine which type of acute leukaemia is present.

 

Further tests

 

There are a number of additional tests that can be used to help reveal more information about the progress and extent of the leukaemia, which can also provide an important insight into how the leukaemia should be treated. These tests are outlined below.

 

Cytogenetic testing

 

Cytogenetic testing involves identifying the genetic makeup of the cancerous cells. There are a number of specific genetic variations that can occur during leukaemia, and knowing what these variations are can have an important impact on treatment. For example, people who have a subtype of acute myeloid leukaemia (AML), known as acute promyelocytic leukaemia, are known to respond well to a medicine called all trans-retinoic acid (ATRA).

 

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 determine how far the leukaemia has spread.

 

CT Scans

 

If you have acute leukaemia, a computerised tomography (CT) scan may be used to check that your organs, such as your heart and lungs, are healthy.

 

Lumbar puncture

 

If is felt that there is a risk that acute leukaemia has spread to your nervous system, a lumbar puncture may be carried out. This 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 then tested to see if the leukaemia has reached your nervous system.

Treatment

Due to the aggressive and rapid nature of acute leukaemia, treatment will usually begin a few days after a diagnosis has been made.

Deciding on a treatment plan

Once leukaemia has been detected, you will need to discuss possible treatment plans. It is likely that the discussion will take place with several doctors, and other health professionals, who each specialise in different aspects of treating leukaemia. These health professionals make up what is known as a multi-disciplinary team (MDT).

A MDT will often include:

  • a haemato-oncologist (a specialist in the non-surgical treatment of leukaemia using techniques such as chemotherapy),
  • a haemato-pathologist (a specialist in the study of cancerous blood cells),
  • a pharmacist,
  • a social worker,
  • a transplant specialist,
  • a microbiologist (a specialist in infectious diseases)
  • a psychologist,
  • a specialist cancer nurse (who will serve as the first point of contact between yourself and the members of the MDT), and
  • a counsellor.

The initial treatment for acute leukaemia usually takes place in a specialist centre, or hospital. If you live in a large urban area, such as London, it is likely that appropriate facilities will be nearby. If you live in a smaller town, or in the countryside, you may have to be treated in a specialist centre in another part of the country.

If your child has leukaemia, and needs to be treated at specialist centre that is not near your home, arrangements can be made that will allow you to stay with your child for some, or all, of their treatment.

The recommended treatment plan will depend on your general health and your age because many of the treatments can cause serious side effects and complications that can put a tremendous strain on the body. Children, teenagers, and adults who are in good health are usually able to withstand an aggressive treatment regime aimed at curing the leukaemia.

Older people with acute leukaemia, or those in poor health, are unlikely to survive such an aggressive approach to treatment. It may therefore be possible to achieve a remission in symptoms, but it may not be possible to cure the leukaemia.

There are several factors that you will need to take into account when deciding on your treatment. They include:

  • your age,
  • the likely progression of your leukaemia,
  • the extent of your leukaemia, and
  • the possible side-effects of treatment.

You will not be rushed into you into making a decision about your treatment plan and, before deciding, you should feel free to talk to as many people as you want, including friends, family, and your partner.

Many people find that writing a list of questions at home to ask the MDT is helpful. Your MDT will be able to recommend what they feel are the best treatment options but, ultimately, the decision will be yours.

Stages of treatment

Treatment for acute leukaemia is carried out in phases. These are described below.

  • Induction - the initial stage of treatment aims 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 - this final stage involves taking regular doses of chemotherapy tablets in order to prevent the leukaemia returning.

Maintenance is not usually used in the treatment of acute myeloid leukaemia (AML) because it only seems to be effective in the treatment of acute lymphoblastic leukaemia (ALL).

Induction

The induction stage of treatment will need to be carried out in hospital, or in a specialist centre. This is because you will probably require regular blood transfusions as it is likely that your blood will not have 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 can be promptly treated. You may also be given antibiotics to further prevent any infection.

You will be given a combination of chemotherapy medication in order to kill the leukaemia cells in your bone marrow. As you will need to receive 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 have to undergo many painful injections.

Some chemotherapy medication may also be directly administered into your cerebrospinal fluid in order to kill any leukaemia cells that may have spread to your nervous system. These are administered by way of a needle that is placed into your spine, in a similar way to a lumbar puncture.

Side-effects from chemotherapy are common. They can include:

  • nausea,
  • vomiting,
  • diarrhoea,
  • loss of appetite,
  • mouth ulcers,
  • tiredness,
  • skin rashes,
  • infertility, and
  • hair loss.

The side-effects should resolve once treatment has finished. Your hair will normally take between 3-6 months to grow back.

If you have the sub-type of AML known as acute promyelocytic leukaemia, you will also be given a medicine called all-trans retinoic acid, or ATRA. ATRA works by changing the immature blast cells into mature healthy blood cells.

Side-effects of ATRA include:

  • headaches,
  • dry mouth and skin,
  • nausea,
  • bone pain, and
  • dry eyes.

If you have the sub-type of ALL, known as Philadelphia chromosome positive ALL, 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 with time. They include:

  • nausea,
  • vomiting,
  • swelling in the face and lower legs,
  • muscle cramps,
  • rash, and
  • diarrhoea.

The induction phase of treatment can last from two weeks to several months, depending on how well you respond to treatment. In some cases, you, or your child, may be able to leave hospital and receive treatment on an out-patient basis if symptoms improve.

Consolidation

Leukaemia can return if only one cancerous cell remains in your body. So the aim of consolidation treatment is to ensure that any remaining leukaemia cells are killed.

Treatment involves receiving regular injections of chemotherapy medications. This is normally done on an out-patient 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 worsen, or if you develop an infection.

The consolidation phase usually lasts several months.

Maintenance

The maintenance phase is designed to act as further insurance against the possibility of the leukaemia returning. It involves taking regular doses of oral chemotherapy medications (tablets) while undergoing regular check-ups to monitor how effective your treatment is proving.

The maintenance phase usually lasts for two years. It is not usually used in the treatment of AML because the evidence shows that taking regular oral chemotherapy medication has little effect in preventing a relapse of AML.

Bone marrow and stem cell transplantation

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 has to undergo aggressive high-dose chemotherapy and radiotherapy in order to destroy any cancerous cells in their body. This can put 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 you, or your child. Usually, the best candidate to provide a donation is 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.

Symptoms

Most of the symptoms of acute leukaemia are caused by the lack of healthy blood cells in your blood supply. Symptoms normally begin slowly and then rapidly escalate in severity as the number of blast cells in your blood increases.

Symptoms of acute leukaemia include:

  • pale skin,
  • tiredness,
  • breathlessness,
  • having repeated infections over a short space of time,
  • unusual and frequent bleeding, such as bleeding gums, or nose bleeds,
  • fever and sweats,
  • bone and joint pain,
  • easily bruised skin,
  • swollen lymph nodes (glands),
  • swollen liver,
  • swollen spleen, and
  • weight loss.

If you, or you child, has some, or all, of these symptoms, it is still highly unlikely that acute leukaemia is the cause.

However you should see your GP as soon as possible because any condition that causes these types of symptoms needs prompt investigation and treatment.

In some cases of acute leukaemia, the affected cells can spread from your blood stream into your central nervous system. This can cause a series of neurological (related to the nervous system) symptoms including:

  • headaches,
  • seizures (fits),
  • vomiting,
  • blurred vision, and
  • dizziness.