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Acute myeloid leukaemia

Leukaemia is cancer of the white blood cells. Symptoms include pale skin, tiredness, breathlessness and repeated infections over a short space of time.

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 – mostly used to fight viral infections
  • myeloid cells – which perform a number of different functions, such as fighting bacterial infections, defending the body against parasites and preventing the spread of tissue damage 

These pages focus on acute myeloid leukaemia, which is cancer of the myeloid cells. The following other types of leukaemia are covered elsewhere:

Warning signs of acute leukaemia

Symptoms of acute myeloid 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
  • tiredness
  • breathlessness
  • having repeated infections over a short space of time
  • unusual and frequent bleeding

Read more about the symptoms of acute myeloid leukaemia.

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 that 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.

Acute leukaemia that is left untreated can prove fatal, as the blood supply will malfunction.

How common is acute myeloid leukaemia?

Acute leukaemia is an uncommon type of cancer. In the UK, around 7,600 people are diagnosed each year with leukaemia. Of those, about 2,300 people have acute myeloid leukaemia.

Acute myeloid leukaemia is more common in people aged 65 or over. For reasons that are not fully understood, it is more common in males than females.

The cause or causes of acute myeloid 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

Read more about the causes of acute myeloid leukaemia.

Outlook

The outlook for people with acute myeloid leukaemia varies depending on the type they have. Some types are more challenging to treat than others. Younger people with the condition tend to have a better outcome than older people.

Chemotherapy is usually given to treat acute myeloid leukaemia. A bone marrow transplant may also be needed to achieve a cure. Read more about the treatment of acute myeloid leukaemia.

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).



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Acute myeloid leukaemia

Most of the symptoms of acute leukaemia are caused by the lack of healthy blood cells in your blood supply. Symptoms usually begin slowly before rapidly

Symptoms of acute myeloid 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 myeloid 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
  • 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 myeloid 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:

  • headaches
  • seizures (fits)
  • vomiting
  • blurred vision
  • dizziness

When to seek medical advice

If you or you 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 GP as soon as possible because any condition that causes these symptoms needs to be promptly investigated and treated.

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Acute myeloid leukaemia

Acute leukaemia begins with an alteration to the structure of deoxyribonucleic acid (DNA) that is found in the stem cells that are responsible for producing

Acute myeloid 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 myeloid 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 X-rays, 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.

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 is that 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.

This theory is 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 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 had chemotherapy and radiotherapy 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.

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Acute myeloid leukaemia

In the initial stages of diagnosing acute leukaemia, your GP will check for physical signs of the condition, such as swollen glands. They will also arrange

In the initial stages of diagnosing acute myeloid leukaemia, your GP 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 local anaesthetic

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.

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. They can also provide an insight into how the leukaemia should be treated. These tests are described 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 type of acute myeloid leukaemia known as acute promyelocytic leukaemia are known to respond well to a medicine called all trans retinoic acid.

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.

CT scans

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

Lumbar puncture

If it is felt that there is a risk that acute leukaemia has spread to your nervous system, a lumbar puncture may be carried out.

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.

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Acute myeloid leukaemia

As acute leukaemia is an aggressive condition that develops rapidly, treatment will usually begin a few days after a diagnosis has been made. Due to the often

As acute myeloid 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 myeloid 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 myeloid leukaemia is carried out in two 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 treat 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.

Induction

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.

Chemotherapy

You will be given a combination of chemotherapy medication 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 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 lumbar puncture.

Side effects that occur following chemotherapy are common. They can include:

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

The side effects should resolve once treatment has finished. Your hair will usually take between three to six months to grow back.

All trans retinoic acid (ATRA)

If you have the sub-type of acute myeloid leukaemia known as acute promyelocytic leukaemia, you will usually also be given a medicine called all trans retinoic acid (ATRA). ATRA works by changing the immature blast cells into mature healthy blood cells, and can reduce symptoms very quickly.

Side effects of ATRA include:

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

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.

Consolidation

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.

Other treatments

There are a number of other treatments that are used in some circumstances. These are described below. 

Radiotherapy

Radiotherapy involves 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 treat advanced cases of acute myeloid leukaemia that have spread to the nervous system and/or brain
  • to prepare the body for a bone marrow transplant (see below)

Side effects of both types of radiotherapy include:

  • hair loss
  • nausea
  • fatigue

The side effects should pass once your course of radiotherapy has been completed. Read more about radiotherapy.

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 amount 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.

Read about Bone marrow transplantation for more information.

Newer unlicensed treatments

If you take part in a clinical trial (see box on this page), you may be offered a drug that is not licensed for use in the UK for acute myeloid leukaemia and is not normally available. Macmillan has information about unlicensed treatments for acute myeloid leukaemia.

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Acute myeloid leukaemia

Having a weakened immune system is a common complication of acute leukaemia. The medical term for having a weakened immune system is immunocompromised. Even

Having a weakened immune system is a common complication of acute leukaemia. The medical term for having a weakened immune system is 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 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.

You should 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 treatment unit because prompt treatment may be required to prevent serious complications. Complications arising from infection are the leading cause of death in people with acute myeloid leukaemia.

Symptoms of infection include:

  • high temperature (fever) of 38C (100.4F) or above
  • headache
  • aching muscles
  • diarrhoea
  • tiredness

Also ensure that all of your vaccinations are up-to-date. Your GP 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

Bleeding

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.

People with advanced acute myeloid leukaemia are more vulnerable to excessive bleeding inside their body, and bleeding is the second most common cause of death in people with the condition.

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
  • vomiting
  • change in mental state, such as confusion

The three 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. Dial 999 to request an ambulance if you suspect that you or your child is experiencing a haemorrhage.

Infertility

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 treatment 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.

Read more about infertility.  

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