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Acute myeloid leukaemia

Page last reviewed: 13/07/2011

Leukaemia is cancer of the white blood cells. Symptoms of leukaemia include:

  • pale skin
  • tiredness
  • breathlessness
  • having repeated infections over a short space of time

Acute leukaemia means that the condition progresses rapidly and aggressively and requires immediate treatment.

These pages focus on acute myeloid leukaemia

Bone marrow

All of the blood cells in the body are produced by bone marrow. Bone marrow is a spongy material that is found inside the bones. It is important because it produces special cells that are 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.

Types of acute leukaemia

Acute leukaemia is classified according to the type of white blood cells that are affected by cancer. There are two main types of white blood cell:

  • lymphocytes - which are 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 

There are two main types of acute leukaemia that are related to the two main types of white blood cells. They are:

  • acute lymphoblastic leukaemia - which is cancer of the lymphocytes
  • acute myeloid leukaemia - which is cancer of the myeloid cells

These pages focus on acute myeloid leukaemia (AML). For information on acute lymphoblastic leukaemia, go to the Health A-Z topic on acute lymphoblastic leukaemia

How common is acute myeloid leukaemia?

Acute leukaemia is an uncommon type of cancer. AML is more common in older people, with most cases occurring in people who are 50 or over. For reasons that are not fully understood, acute leukaemia is more common in boys and men than it is in girls and women.

The cause or causes of acute leukaemia are uncertain, but known risk factors include:

  • exposure to high levels of radiation
  • exposure to benzene, which is a chemical that is used in manufacturing and is also found in cigarettes

Outlook

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

Treatments for acute leukaemia usually involve a combination of chemotherapy and radiotherapy. In some cases, a bone marrow transplant may also be used to achieve a cure.

If a cure is not possible, there is a risk that the lack of healthy blood cells can make people 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)

Bone marrow


Bone marrow is the soft, spongy tissue in the centre of bones that produces blood cells.

Blood


Blood supplies oxygen to the body and removes carbon dioxide. It is pumped around the body by the heart.

Acute


Acute means occurring suddenly or over a short period.

Chronic


Chronic usually means a condition that continues for a long time or keeps coming back.

Stem cells


Stem cells are cells that are at an early stage of development, so they still have the ability to turn into any type of cell in the body.

Oxygen

Oxygen is an odourless, colourless gas that makes up about 20% of the air we breathe.

Bacteria

Bacteria are tiny, single-celled organisms that live in the body. Some can cause illness and disease and others are good for you.

Tissue

Body tissue is made up of groups of cells that perform a specific job, such as protecting the body against infection, producing movement or storing fat.

Chemotherapy

Chemotherapy is the treatment of illness or disease with a chemical substance. It is used, for example in the treatment of cancer.

 

Remission

Remission is when the symptoms of a condition are reduced (partial remission) or go away completely (complete remission).

 

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Page last reviewed: 13/07/2011

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 escalating 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
  • 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 lost

In some cases of acute 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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Page last reviewed: 13/07/2011

Genetic mutation

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 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 leukaemia cases are caused by related genetic disorders. For example, rates of leukaemia tend to be higher in children with Down's syndrome (a genetic condition that affects normal physical development and causes mild to moderate learning difficulties).

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.

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 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 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 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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Page last reviewed: 13/07/2011

Blood tests

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 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 indicates abnormal results, you will be referred to a haematologist (a specialist in treating blood conditions).

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 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 subtype of acute myeloid leukaemia (AML), also 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 (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 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.

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

Your treatment plan

Due to 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 (MDT). 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 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.

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 that you will not need to have 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. 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 (AML) 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.

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. 

Dasatinib

Dasatinib is a new type of medication that is used to treat a sub-type of acute myeloid leukaemia, known as Philadelphia chromosome positive AML, when all other treatments have proved unsuccessful.

Dasatinib is a tyrosine kinase inhibitor. This means that 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. Dasatinib is taken orally (in tablet form).

Common side effects of dasatinib include:

  • diarrhoea
  • headache
  • rash or red, dry, itchy skin
  • a build-up of fluids in the body, such as around your legs or face
  • fatigue
  • breathlessness
  • nausea
  • bone and muscle pain

Dasatinib can lead to a sudden drop in the number of blood cells. This means that you will become vulnerable to developing an infection and it is likely that you will bruise and bleed more easily.

See Acute leukaemia - Complications for more information and advice about vulnerability to infection and bleeding.

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 AML 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. 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.

See the Health A-Z topics about Cataracts and Cataract surgery for more information.

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.

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Page last reviewed: 13/07/2011

Immunocompromised

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 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.

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 GP or care team 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 (AML).

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 be  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 AML 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 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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Content provided by NHS Choices www.nhs.uk and adapted for Ireland by the Health A-Z.

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