Acute myeloid leukaemia
Acute myeloid leukaemia
Leukaemia is cancer of the white blood cells. Acute leukaemia means the condition progresses rapidly and aggressively, requiring immediate treatment.
Acute leukaemia is classified according to the type of white blood cells that are affected. 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 (AML), which is an aggressive cancer of the myeloid cells. The following types of leukaemia are covered separately:
acute lymphoblastic leukaemia
chronic myeloid leukaemia
chronic lymphocytic leukaemia
Signs and symptoms of acute myeloid leukaemia
The symptoms of AML usually develop over a few weeks, and become increasingly more severe. Symptoms can include:
unusual and frequent bleeding, such as bleeding gums ornosebleeds
In more advanced cases, AML can make you extremely vulnerable to life-threatening infections or serious internal bleeding.
Seeking medical advice
You should see your GP if you or your child have possible symptoms of AML. Although it is highly unlikely that leukaemia is the cause, these symptoms should be investigated.
If your GP thinks you may have leukaemia, they will arrange for blood tests to check your white blood cells. If this test suggests there is a problem, you will be urgently referred to a haematologist (a specialist in treating blood conditions) for further tests and any necessary treatment.
What causes acute myeloid leukaemia?
AML occurs when specialised cells called stem cells, which are found in the bone marrow (a spongy material inside the bones), produce excessive numbers of immature white blood cells. These immature cells are known as blast cells.
Blast cells don't have the infection-fighting properties of healthy white blood cells, and their excessive production can lead to a decrease in the number of red blood cells (which carry oxygen in the blood) and platelets (cells that help the blood to clot).
It is not clear exactly why this happens, although a number of factors that can increase your risk of developing AML have been identified. These include:
exposure to very high levels of radiation, including previous treatment with radiotherapy
exposure to benzene – a chemical used in manufacturing that is also found in cigarette smoke
having an underlying blood disorder or genetic condition (such asDown's syndrome)
Who is affected
AML is an uncommon type of cancer. Around 2,600 people are diagnosed with the condition each year in the UK.
AML can develop at any age, but it's more common in people over the age of 60.
How acute myeloid leukaemia is treated
AML is an aggressive type of cancer that can develop rapidly, so treatment usually needs to begin soon after a diagnosis is confirmed.
The main treatment for AML is chemotherapy, which is used to kill as many leukaemia cells in your body as possible and reduce the risk of the condition coming back (relapsing).
In some cases, intensive chemotherapy and radiotherapy may be needed, in combination with a bone marrow or stem cell transplant, to achieve a cure.
The outlook for AML largely depends on the specific type of AML you have, your age and general health.
There are many subtypes of AML, which are classified according to a number of features – such as the specific genetic changes in the leukaemia cells. Some types of AML are more challenging to treat than others.
Even if treatment is initially successful, there remains a significant risk that the condition will return at some point during the next few years. If this happens, treatment may need to be repeated.
A number of recent medical trials have suggested that almost half of those aged under 60 diagnosed with AML will live for at least five years, and in some types of AML, such as acute promyeloid leukaemia (APML), around 85% will live for at least five years.
In general, the outlook for children with AML tends to be better than that of adults diagnosed with the condition.
Symptoms of acute myeloid leukaemia
The symptoms of acute myeloid leukaemia (AML) usually develop over a few weeks, becoming more severe as the number of immature white blood cells (blast cells) in your blood increases.
Symptoms of AML can include:
a high temperature (fever)
unusual and frequent bleeding, such as bleeding gums or nosebleeds
easily bruised skin
flat red or purple spots on the skin (petechiae)
bone and joint pain
a feeling of fullness or discomfort in your tummy (abdomen), caused by swelling of the liver or spleen
In rare cases of AML, the affected cells can spread into the central nervous system. This can cause symptoms such as headaches, fits (seizures), vomiting, blurred vision and dizziness.
When to seek medical advice
You should see your GP if you or your child have the symptoms listed above.
Although it is highly unlikely that AML is the cause, any condition that causes these symptoms needs to be promptly investigated and treated.
Causes of acute myeloid leukaemia
Acute myeloid leukaemia (AML) is caused by a DNA mutation in the stem cells that produce red blood cells, platelets and infection-fighting white blood cells.
This mutation causes the stem cells to produce many 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 fully developed white blood cells. These immature cells are known as "blast cells".
As the number of immature cells increases, the amount of healthy red blood cells and platelets fall, and it's this fall that causes many of the symptoms of chronic leukaemia.
It is not known what triggers the genetic mutation in AML, although a number of different factors that can increase your risk of developing the condition have been identified.
The main risk factors for AML are outlined below.
Being exposed to a significant level of radiation can increase your chances of developing AML, although this usually requires exposure at very high levels. For example, rates of AML are higher in people who survived the atomic bomb explosions in Japan in 1945.
Most people in the UK are very unlikely to be exposed to levels of radiation high enough to cause AML, except for some people who have had radiotherapy as part of their treatment for a previous cancer (see below).
Benzene and smoking
Exposure to the chemical benzene is a known risk factor for AML in adults. This chemical is found in petrol, and is also used in the rubber industry, although there are strict controls to protect people from prolonged exposure.
Benzene is also found in cigarette smoke, which could explain why people who smoke have an increased risk of developing AML.
Previous cancer treatment
Treatment with radiotherapy and certain chemotherapy medications for an earlier, unrelated cancer can increase your risk of developing AML many years later.
When leukaemia develops because of previous cancer treatment, it is called secondary leukaemia or treatment-related leukaemia.
People with certain blood disorders, such as myelodysplasia, myelofibrosis or polycythaemia vera (PCV), have an increased risk of developing AML.
People with certain genetic disorders, including Down’s syndrome and Fanconi’s anaemia, have an increased risk of developing leukaemia.
Other suggested triggers
A number of other environmental factors that could trigger AML have also been suggested, including childhood vaccinations and living near a nuclear power station or a high-voltage power line. However, there is no clear evidence to suggest that these can increase your risk of developing AML.
Diagnosing acute myeloid leukaemia
In the initial stages of diagnosing acute myeloid leukaemia (AML), your GP will check for physical signs of the condition and arrange for you to have blood tests.
A high number of abnormal white blood cells, or a very low blood count in the test sample, could indicate the presence of leukaemia. If this is the case, you will be urgently referred to a haematologist (a specialist in treating blood conditions).
A haematologist may carry out further blood tests, in addition to some of the tests outlined below.
Bone marrow biopsy
To confirm a diagnosis of AML, 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, which 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 thin needle to remove a sample of liquid bone marrow. In some cases, a larger needle may also be used to remove a small amount of bone and bone marrow together.
The procedure is usually very well tolerated, but may cause some bruising and discomfort for a few days afterwards in a minority of people. 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 can also determine the type of leukaemia you have.
There are additional tests that can be used to help reveal more information about the progress and extent of your AML. They can also provide an insight into how the condition should be treated. These tests are described below.
Genetic tests can also be carried out on blood and bone marrow samples to identify the genetic makeup of the cancerous cells. There are many specific genetic variations that can occur in AML, and knowing the exact type of AML you have can help doctors decide the most appropriate treatment.
For example, people who have a type of AML known as acute promyelocytic leukaemia (APML) are known to respond well to a medicine called All Trans-Retinoic Acid (ATRA).
If you have AML, a computerised tomography (CT) scan, X-ray or echocardiogram (an ultrasound scan of the heart) may be used to check that your organs, such as your heart and lungs, are healthy.
These tests are carried out because it is important for doctors to assess your general health before they can decide on the most appropriate treatment for you.
In the rare situations where it is believed there is a risk that AML has spread to your nervous system, a lumbar puncture may be carried out. In this procedure, a needle is used to extract a sample of cerebrospinal fluid (which surrounds and protects your spine) from your back, so it can be checked for cancerous cells.
If cancerous cells are found in your nervous system, you may need to have injections of chemotherapy medication directly into your cerebrospinal fluid as part of your treatment.
Treating acute myeloid leukaemia
Acute myeloid leukaemia (AML) is an aggressive condition that develops rapidly, so treatment will usually begin a few days after a diagnosis has been confirmed.
As AML is a complex condition, it is usually treated by a multidisciplinary team (MDT) – a group of different specialists working together.
Your treatment plan
Treatment for AML is often carried out in two stages:
Induction – the aim of this initial stage of treatment is to kill as many leukaemia cells in your bone marrow and blood as possible, restore your blood to proper working order and treat any symptoms you may have.
Consolidation – this stage aims to prevent the cancer returning (relapsing), by killing any remaining leukaemia cells that may be present in your body.
The induction stage of treatment is not always successful and sometimes needs to be repeated before consolidation can begin.
If you have a relapse after treatment, both reinduction and consolidation may need to be carried out. This may be the same as your first treatment, but if the relapse is a number of years later, it is likely to involve different medications or a stem cell transplant (see below).
If you are thought to have a high risk of experiencing complications of AML treatment – for example, if you are over 75 years of age or have another underlying health condition – less intensive chemotherapy treatment may be carried out. This is less likely to successfully kill all of the cancerous cells in your body, but it can help control your condition.
The initial treatment you have for AML will largely depend on whether you are fit enough to have intensive chemotherapy, or whether treatment at a lower dosage is recommended.
If you can have intensive induction chemotherapy, this will usually involve being given a combination of chemotherapy medication at a high dose, to kill the cancerous cells in your bone marrow and blood.
This stage of treatment will be carried out in hospital or in a specialist centre, as you will require very close medical and nursing supervision.
You will have regular blood transfusions, as your blood is unlikely to contain enough healthy blood cells.
You will also be vulnerable to infection, so it is important you are in a clean and stable environment where your health can be carefully monitored and any infection you have can be promptly treated. You may also be prescribed antibiotics to help prevent further infection.
Depending on how well you respond to treatment, the induction phase can last from four weeks to a couple of months. You may be able to leave hospital and receive treatment on an outpatient basis if your symptoms improve.
For intensive treatment, the chemotherapy medications will be injected into a thin tube that is inserted either into a blood vessel near your heart (central line) or into your arm (a peripherally inserted central catheter or PICC).
In very rare cases, 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 done using a needle that is placed into your spine, in a similar way to a lumbar puncture.
Side effects of intensive chemotherapy for AML are common. They can include:
loss of appetite
sore mouth and mouth ulcers (mucositis)
infertility – which may be temporary or permanent (seecomplications of AML for more information)
Most side effects should resolve once treatment has finished. You should tell your care team if side effects become particularly troublesome, as there are medicines that can help you cope better with certain side effects.
If your doctors don’t think you are fit enough to withstand the effects of intensive chemotherapy, they may recommend having non-intensive treatment. This involves giving the same combination of medications used in intensive chemotherapy, but at lower doses.
The main aim of this treatment is to control the level of cancerous cells in your body and limit any symptoms you are experiencing, while reducing your risk of experiencing significant side effects of treatment.
The medications used during non-intensive chemotherapy may be given through a drip into a vein, by mouth or by injection under the skin, and can often be given on an outpatient basis.
All Trans-Retinoic Acid (ATRA)
If you have the sub-type of acute myeloid leukaemia known as acute promyelocytic leukaemia, you will usually be given capsules of a medicine called ATRA, in addition to chemotherapy.
ATRA works by changing the immature white blood cells (blast cells) into mature healthy cells, and can reduce symptoms very quickly.
Side effects of ATRA can include headaches, nausea, bone pain, anddry mouth, skin and eyes.
If induction is successful, the next stage of treatment will be consolidation.
This often involves receiving regular injections of chemotherapy medication that are usually given 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.
There are many other treatments that are used, which are described below.
Radiotherapy involves using high doses of controlled radiation to kill cancerous cells. There are two main reasons why radiotherapy is usually used to treat AML:
to prepare the body for a bone marrow or stem cell transplant (see below)
to treat advanced cases that have spread to the nervous system and/or brain, although this is uncommon
Side effects of both types of radiotherapy can include hair loss, nausea and fatigue. The side effects should pass once your course of radiotherapy has been completed.
Bone marrow and stem cell transplants
If chemotherapy is not effective, a possible alternative treatment option is a bone marrow or stem cell transplant.
Before transplantation can take place, the person receiving the transplant will need to have intensive high-dose chemotherapy and radiotherapy to destroy the cells in their bone marrow. The donated stem cells are then given through a tube into a blood vessel, in a similar way to chemotherapy medication.
This process can put an enormous amount of strain on the body and cause significant side effects and potential complications, so you will usually need to stay in hospital for a few weeks.
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.
Because of this, transplantations are most successful when they are carried out in children and young people, or older people who are in otherwise good health, and when there is a suitable donor, such as a brother or sister.
Clinical trials and newer unlicensed treatments
In the UK, a number of clinical trials are currently underway that aim to find the best way of treating AML. Clinical trials are studies that use new and experimental techniques to see how well they work in treating, and possibly curing, acute leukaemia.
As part of your treatment, your care team may suggest taking part in a clinical trial to help researchers learn more about the best way to treat your AML, and AML in general. Search for clinical trials for AML.
If you take part in a clinical trial, you may be offered a drug that is not licensed for use in the UK and is not normally available. However, there is no guarantee that the techniques being studied in the clinical trial will be more effective than current treatments.
Your care team can tell you whether there are any clinical trials available in your area, and can explain the benefits and risks involved.
Complications of acute myeloid leukaemia
If you have acute myeloid leukaemia (AML), you may experience a number of complications. These can be caused by the condition itself, although they can also occur as a side effect of treatment.
Some of the main complications associated with AML are outlined below.
Weakened immune system
Having a weakened immune system – being immunocompromised – is a common complication of AML.
Even if your blood is restored to normal working order with treatment, many of the medications that are used to treat AML can temporarily weaken your immune system.
This means you are more vulnerable to developing an infection, and any infection could be more serious than usual. Complications arising from infection are the leading cause of death in people with AML.
Therefore, you may be advised to:
take regular doses of antibiotics to prevent bacterial infections
maintain good personal and dental hygiene
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
check with your GP to ensure that all of your vaccinations are up to date, although you will not be able to have any vaccine containing "live" viruses or bacteria, such as the shingles vaccine and the MMR vaccine (against measles, mumps and rubella)
You should report any possible symptoms of an infection to your treatment unit immediately, as prompt treatment may be required to prevent complications.
Symptoms of an infection can include:
a high temperature (fever)
If you have AML, 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, which is the second most common cause of death in people with the condition.
Serious bleeding can occur:
inside the skull (intracranial haemorrhage) – causing symptoms such as a severe headache, stiff neck, vomiting and confusion
inside the lungs (pulmonary haemorrhage) – causing symptoms such as coughing up blood, breathing difficulties and a bluish skin tone (cyanosis)
inside the stomach (gastrointestinal haemorrhage) – causing symptoms such as vomiting blood and passing stools (faeces) that are very dark or tar-like in colour
All these types of haemorrhage should be regarded as a medical emergency. You should dial 999 immediately and ask for an ambulance if you suspect a haemorrhage is occurring.
Many of the treatments that are used to treat acute leukaemia can cause infertility. This is often temporary, but in some cases can be permanent.
People who are particularly at risk of permanent infertility are those who have received high doses of chemotherapy and radiotherapy in preparation for a bone marrow or stem cell transplant.
Your treatment team can give 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 their sperm samples stored. Similarly, women can have eggs or fertilised embryos stored, which can then be placed back into their womb, following treatment.
However, as AML is an aggressive condition that develops rapidly, there may not always be time to do this before treatment needs to start