Acute myeloid leukaemia

Leukaemia is cancer of the white blood cells. Acute leukaemia means it progresses rapidly and aggressively, and usually requires immediate treatment.

Acute leukaemia is classified according to the type of white blood cells affected. The two main types of white blood cells are:

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 

Signs and symptoms of AML

• The symptoms of AML usually develop over a few weeks and become increasingly more severe. Symptoms can include:
• pale skin
• tiredness
• breathlessness
• frequent infections
• unusual and frequent bleeding, such as bleeding gums or nosebleeds

In more advanced cases, AML can make you extremely vulnerable to life-threatening infections or serious internal bleeding.

Read more about the complications of AML.

Seeking medical advice

You should see your GP if you or your child have possible symptoms of AML. Although it's highly unlikely that leukaemia is the cause, these symptoms should be investigated.

If your GP thinks you may have leukaemia, they'll arrange blood tests to check your blood cell production. If the tests suggest there's a problem, you'll be urgently referred to a haematologist (a specialist in treating blood conditions) for further tests and any necessary treatment.

Read more about diagnosing AML.

What causes AML?

AML occurs when specialised cells called stem cells, which are found in the bone marrow (a spongy material inside the bones), produce too many 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 producing too many 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's not clear exactly why this happens and, in most cases, there's no identifiable cause. However, a number of factors that can increase your risk of developing AML have been identified. These include:

• previous chemotherapy or radiotherapy
• exposure to very high levels of radiation (including previous  radiotherapy treatment)
• exposure to benzene – a chemical used in manufacturing that's also found in cigarette smoke
• having an underlying blood disorder or genetic disorder, such as Down's syndrome

Read more about the causes of AML.

Who's affected

AML is a rare type of cancer, with around 2,600 people diagnosed with it each year in the UK.

The risk of developing AML increases with age. It's most common in people over 65.

How AML 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.

Chemotherapy is the main treatment for AML. It's 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.

Read more about treating AML.

Outlook

The outlook for AML largely depends on the specific type of AML you have, as well as your age and general health.

There are many subtypes of AML, which are classified according to various 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's still 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 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

Causes

Acute myeloid leukaemia (AML) is caused by a DNA mutation in the stem cells in your bone marrow that produce red blood cells, platelets and infection-fighting white blood cells.

The mutation causes the stem cells to produce many more white blood cells than are needed.

The white blood cells produced are still immature, so they don't 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 decrease, and it's this fall that causes many of the symptoms of leukaemia.

Increased risk

It's 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.

Radiation exposure

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.

In the UK, most people are unlikely to be exposed to levels of radiation high enough to cause AML. However, some people who have had radiotherapy as part of their treatment for previous cancer (see below) can be the exception.

Benzene and smoking

Exposure to the chemical benzene is a known risk factor for AML in adults. Benzene is found in petrol, and it's 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.

Leukaemia that develops as a result of previous cancer treatment is called "secondary leukaemia" or "treatment-related leukaemia".

Blood disorders

People with certain blood disorders – such as myelodysplasia, myelofibrosis or polycythaemia vera (PCV) – have an increased risk of developing AML.

Genetic disorders

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's no clear evidence to suggest that these can increase your risk of developing AML.

Diagnosis

Treatment

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's usually treated by a multidisciplinary team (MDT) – a group of different specialists working together (see below).

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 blood and bone marrow 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 isn't always successful and sometimes needs to be repeated before consolidation can begin.

If you have a relapse after treatment, both re-induction and consolidation may need to be carried out. This may be the same as your first treatment, although it's likely to involve different medications or a stem cell transplant (see below).

If you're thought to have a high risk of experiencing complications of AML treatment – for example, if you're 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. 

Induction

The initial treatment you have for AML will largely depend on whether you're fit enough to have intensive chemotherapy, or whether treatment at a lower dosage is recommended.

Intensive chemotherapy

If you can have intensive induction chemotherapy, you'll usually be given a combination of chemotherapy medication at a high dose to kill the cancerous cells in your blood and bone marrow.

This stage of treatment will be carried out in hospital or in a specialist centre, as you'll need very close medical and nursing supervision.

You'll have regular blood transfusions because your blood won't contain enough healthy blood cells.

You'll also be vulnerable to infection, so it's important that you're 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's 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's placed into your spine, in a similar way to a lumbar puncture.

Side effects of intensive chemotherapy for AML are common. They can include: 

• nausea
• vomiting
• diarrhoea
• loss of appetite
• sore mouth and mouth ulcers (mucositis)
• tiredness
• skin rashes
• hair loss
• infertility – which may be temporary or permanent (see complications of AML for more information)

Most side effects should resolve once treatment has finished. Tell a member of your care team if side effects become particularly troublesome, as there are medicines that can help you cope better with certain side effects.

Read more about the side effects of chemotherapy.

Non-intensive chemotherapy

If your doctors don’t think you're fit enough to withstand the effects of intensive chemotherapy, they may recommend non-intensive treatment. This involves using an alternative type of chemotherapy to the standard intensive therapy, which is designed more to control leukaemia rather than cure it.

The main aim of this treatment is to control the level of cancerous cells in your body and limit any symptoms you have, 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 AML known as acute promyelocytic leukaemia, you'll 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, and dry mouth, skin and eyes.

Consolidation

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 won't have to stay in hospital overnight. However, you may need 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

Many other treatments are used for AML, as 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 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 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 doesn't work, 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 possibly radiotherapy to destroy the cells in their bone marrow. The donated stem cells are 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'll 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 receiving the donation. The best candidate to provide a donation is usually a brother or sister with the same tissue type.

Transplantations are most successful when they're carried out on children and young people, or older people who are otherwise in good health, and when there's a suitable donor, such as a brother or sister.

Read about bone marrow donation.

Azacitidine

Azacitidine is a possible alternative treatment for adults with AML who can't have a stem cell transplant.

It's recommended by the National Institute for Health and Care Excellence (NICE) for use in certain circumstances – for example, depending on the characteristics of the person's blood and bone marrow.

Azacitidine is a chemotherapy medication that's given by injection under the skin. It interferes with the growth of cancer cells and destroys them, and also helps bone marrow to produce normal blood cells.

NICE has more information about azacitidine for the treatment of AML.

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, AML.

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 medication that isn't licensed for use in the UK and isn't normally available. However, there's no guarantee that the techniques being studied in the clinical trial will work better 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.

Macmillan has more information about unlicensed treatments for AML.

Complications