Acute myeloid leukaemia is where the bone marrow makes large numbers of abnormal immature white blood cells which are derived from a myeloid stem cell.
What is acute myeloid leukaemia?
Acute myeloid leukaemia (AML) is a condition where the bone marrow makes large numbers of abnormal immature white blood cells which are derived from a myeloid stem cell. The abnormal immature cells are called blasts.
There are various subtypes of AML, depending on exactly what cell type becomes cancerous and at what stage in the maturing process. There are eight main subtypes which are called M0, M1, M2, etc, up to M7. These are sometimes called more descriptive names such as acute myelomonocytic leukaemia (this is M4 where the blast cell is one which would normally have developed into a monocyte) and AML with minimal evidence of myeloid differentiation (this is M0 where the blast cell is a very immature cell), etc.
Typically, AML develops quite quickly (acutely) and rapidly becomes worse (over a few weeks or so) unless treated.
Who develops acute myeloid leukaemia?
AML is an uncommon disease and affects about 2,000 adults and about 50 children in the UK each year. Most cases occur in people aged over 50. It is slightly more common in men than in women.
AML is rare in people under the age of 20.
What causes acute myeloid leukaemia?
A leukaemia is thought to start first from one abnormal cell. What seems to happen is that certain vital genes, which control how cells divide, multiply and die, are damaged or are altered. This makes the cell abnormal. If the abnormal cell survives it may multiply out of control and develop into a leukaemia.
In most cases of AML, the reason why an immature white blood cell becomes abnormal is not known. There are certain risk factors which increase the chance that leukaemia will develop, but these only account for a small number of cases. Risk factors known for AML include:
- High-dose radiation (for example, previous radiotherapy for another condition).
- Exposure to the chemical benzene (this is in cigarettes).
- Some genetic conditions which can increase the risk of having AML in the future. The most common is Down's syndrome.
AML is not an inherited condition and does not run in families.
What are the main initial symptoms and problems?
As large numbers of abnormal blast cells are made, much of the bone marrow fills with these abnormal cells. Because of this it is difficult for normal cells in the bone marrow to survive and make enough normal blood cells. Also, the abnormal cells spill out into the bloodstream. Therefore, the main problems which can develop include:
- Anaemia. This occurs as the number of red blood cells goes down. This can cause tiredness, breathlessness and other symptoms. You may also look pale.
- Blood clotting problems. This is due to low levels of platelets. This can cause easy bruising, bleeding from the gums and other bleeding-related problems.
- Serious infections. The abnormal blast cells do not protect against infection. Also, there is a reduced number of normal white blood cells which usually combat infection. Therefore, serious infections are more likely to develop. The symptoms can vary greatly, depending on the type and site of infection.
The abnormal blasts may also accumulate in other sites. You may therefore develop swollen glands, an enlarged spleen or liver and, occasionally, other rare symptoms. Other common symptoms include pain in the bones or joints, persistent high temperature (fever) and weight loss. Left untreated, AML usually causes death within a few months.
How is acute myeloid leukaemia diagnosed and assessed?
A blood test
A blood test can often suggest the diagnosis of AML. The test will typically show a low number of red blood cells, normal white blood cells and platelets. Some blast cells which have spilled into the bloodstream from the marrow are also usually seen. Sometimes large numbers of blast cells occur in the bloodstream. Further tests are usually done to confirm the diagnosis.
A bone marrow sample
For this test a small amount of bone marrow is removed by inserting a needle into the pelvic bone (or sometimes the breastbone (sternum)). Local anaesthetic is used to numb the area. Sometimes a small core of marrow will also be taken (a trephine biopsy). The samples are put under the microscope to look for abnormal cells and also tested in other ways. This can confirm the diagnosis. See separate leaflet called Bone Marrow Biopsy and Aspiration for more details.
Cell and chromosome analysis
Detailed tests are done on abnormal blast cells obtained from the bone marrow sample or blood test. The chromosomes within the cells are checked for certain changes. Chromosomes are the parts in the cell which contain DNA - the genetic make-up of the cell. Various subtypes of AML can be diagnosed by detecting changes which occur to parts of one or more chromosomes. (These chromosome changes only occur in the leukaemia cells, not the normal body cells.) It is important to know the exact subtype of AML, as the treatments and outlook (prognosis) can vary depending on the type.
Various other tests
A lumbar puncture is done if symptoms suggest that the abnormal cells have spread to the brain or spinal cord. This test collects a small amount of fluid from around the spinal cord - cerebrospinal fluid (CSF). It is done by inserting a needle between the vertebrae in the lower (lumbar) region of the back. The fluid is examined for leukaemia cells. A chest X-ray, blood tests, and other tests are done to assess your general well-being.
What is the treatment for acute myeloid leukaemia?
The aim of treatment is to kill all the abnormal cells. This then allows the bone marrow to function normally again and produce normal blood cells. The main treatment is chemotherapy. A stem cell transplant (SCT) is used in some cases.
The exact treatment regime used in each case (the medicines used, doses, length of treatment, etc) takes into account various factors. This is based on research trials which aim to determine the best treatment for the various subtypes of AML. Research trials continue to try to find even better treatments. The factors which are taken into account include:
- The exact subtype of AML.
- Your age, sex and general health.
- The number of blasts in the blood at diagnosis.
- How well the condition responds to the initial phase of treatment (see below).
- Whether the leukaemia is a secondary complication from a previous bone marrow problem.
- Whether the leukaemia has spread to the brain and/or spinal cord.
On the basis of these factors, people with AML are classed as low-risk, standard-risk or high-risk. That is, the risk of the leukaemia coming back (relapsing) after standard treatment. The type and intensity of treatment given can depend on your risk classification. For example, more intensive treatment is usually offered if your risk is high.
Chemotherapy is a treatment which uses anti-cancer medicines to kill cancer cells, or to stop them from multiplying. See separate leaflet called Chemotherapy for more details.
As many doses of medicines are likely to be given straight into a vein (intravenously) over a prolonged period, it is usual for a plastic tube to be put into a large blood vessel. This can be a central line in a vein in your chest or a peripheral line in your arm (sometimes called a central line or PICC line). It can be left in place for months until the course of treatment is finished. This means you do not need repeated injections. Medicines can be injected or dripped through the line from time to time when a dose is due.
Usually, the course of chemotherapy is given in cycles. A cycle is a spell of treatment followed by a rest from treatment. The rest from treatment allows your body to recover from any side-effects and gives a chance for damaged normal cells to recover before the next spell of treatment.
The length of a full course of treatment is often about six months. A full course of treatment can vary depending on your circumstances.
Chemotherapy for AML is usually divided into two phases.
- Induction phase. This is the first few cycles of treatment. This aims to kill the majority of the leukaemia cells. At the end of this phase there are usually no leukaemia cells detectable in a blood sample or in a bone marrow sample. This is called being in remission. Remission does not mean cure. It means that no abnormal cells can be detected by tests.
- Consolidation (intensification) phase. This is the remaining cycle of treatment and the medicines used may be different. This phase of treatment aims to kill any remaining leukaemia cells which may still be present (but not detected by any tests).
New types of chemotherapy are being tested in clinical trials. You may be offered to take part in a clinical trial. Your doctor will give you more information about this.
All-trans retinoic acid
If you have a type of AML called acute promyelocytic leukaemia (APL) then it is likely you will be also given a medicine called all-trans retinoic acid (ATRA). This is a specialised form of vitamin A and is also known as tretinoin. ATRA is given for up to three months with chemotherapy. It makes the leukaemia cells mature (differentiate) and this then rapidly improves leukaemia symptoms.
Stem cell transplant (STC)
An SCT - sometimes called bone marrow transplant - is sometimes used, depending on the type of the AML. For example, it may be used in types classed as high-risk and in some cases where the leukaemia has recurred (relapsed) following treatment with usual chemotherapy. See separate leaflet called Stem Cell Transplant for more details.
Other treatments include:
- Antibiotics or antifungal medicines if infection occurs.
- Blood and platelet transfusions to improve low levels of red blood cells and platelets.
- General supportive measures to overcome side-effects of chemotherapy.
Treatment of relapses
Despite treatment, in some cases the AML returns sometime after treatment ends. Relapses are treated in a similar way to the initial treatment but the treatment regime is often more intensive and may include an SCT.
Side-effects from chemotherapy
Side-effects during treatment
The medicines used for chemotherapy are powerful and often cause unwanted side-effects. The medicines work by killing cells which are dividing and so some normal cells are damaged too. Side-effects vary from medicine to medicine and your doctor will advise. The most common side-effects are feeling sick (nausea), loss of hair and an increased risk of infection (as the normal white blood cells are affected by treatment). Anti-sickness medicines are commonly used to prevent nausea.
In a small number of cases, problems develop months or years after a period of intensive chemotherapy. For example, treatment may affect fertility or the function of certain hormone-producing glands. There is also a small increased risk of developing a different cancer later in life.
Your doctor will advise on the possible risks and side-effects of your treatment regime.
What is the outlook?
In general, the outlook (prognosis) is poor but it has improved in recent years as treatments continue to improve. It is difficult to give exact figures. However, the chance of a good response to treatment varies. It depends on factors such as the exact type of the AML and your age. For example, for people under the age of 60, there is a good chance of a cure where the AML is classed as low-risk.
The outlook is generally not as good for people over the age of 60. This is partly because older people may not be able to tolerate intensive chemotherapy as well as younger people do. Also, because some cases in older people are secondary to a previous bone marrow problem, and these tend to respond less well to treatment.
The treatment of cancer and leukaemia is a developing area of medicine. New treatments continue to be developed and the information on outlook above is very general. The specialist who knows your case can give more accurate information about the outlook for your particular situation.
Further reading and references
Childhood Acute Lymphoblastic Leukemia Treatment; National Cancer Institute
Acute myeloblastic leukaemias in adult patients: ESMO Clinical Practice Guidelines for diagnosis treatment and follow-up; European Society for Medical Oncology (Aug 2013)
Eichhorst B, Robak T, Montserrat E, et al; Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015 Sep26 Suppl 5:v78-84. doi: 10.1093/annonc/mdv303.
Chronic myeloid leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up; European Society for Medical Oncology (2017)
Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up; European Society for Medical Oncology (2015)