What is leukaemia?
Leukaemia is a cancer of cells in the bone marrow (the cells which develop into blood cells).
Cancer is a disease of the cells in the body. There are many types of cancer which arise from different types of cell. What all cancers have in common is that the cancer cells are abnormal and do not respond to normal control mechanisms. Large numbers of cancer cells build up because they multiply ‘out of control’, or because they live much longer than normal cells, or both.
With leukaemia, the cancerous cells in the bone marrow spill out into the bloodstream. There are several types of leukaemia. Most types arise from cells which normally develop into white blood cells. (The word leukaemia comes from a Greek word which means ‘white blood’.) If you develop leukaemia it is important to know exactly what type it is. This is because the outlook (prognosis) and treatments vary for the different types. Before discussing the different types of leukaemia it may help to know some basics about normal blood cells and how they are made.
What is normal blood made up of?
- Blood cells, which can be seen under a microscope, make up about 40% of the blood’s volume. Blood cells are divided into three main types:
- Red cells (erythrocytes). These make blood a red colour. One drop of blood contains about five million red cells. Red cells contain a chemical called haemoglobin. This binds to oxygen, and takes oxygen from the lungs to all parts of the body.
- White cells (leukocytes). There are different types of white cells which are called neutrophils (polymorphs), lymphocytes, eosinophils, monocytes and basophils. They are part of the immune system. Their main role is to defend the body against infection.
- Platelets. These are tiny and help the blood to clot if we cut ourselves.
- Plasma is the liquid part of blood and makes up about 60% of the blood’s volume. Plasma is mainly made from water, but contains many different proteins and other chemicals, such as hormones, antibodies, enzymes, glucose, fat particles, salts, etc.
When blood spills from your body (or a blood sample is taken into a plain glass tube) the cells and certain plasma proteins clump together to form a clot. The remaining clear fluid is called serum.
The bone marrow, stem cells and blood cell production
Blood cells are made in the bone marrow by ‘stem’ cells. The bone marrow is the soft ‘spongy’ material in the centre of bones. The large flat bones, such as the pelvis and breast-bone (sternum), contain the most bone marrow. To make blood cells constantly you need a healthy bone marrow. You also need nutrients from your diet, including iron and certain vitamins.
Stem cells are primitive (immature) cells. There are two main types in the bone marrow – myeloid and lymphoid stem cells. These derive from even more primitive common ‘pleuripotent’ stem cells. Stem cells constantly divide and produce new cells. Some new cells remain as stem cells and others go through a series of maturing stages (‘precursor’ or ‘blast’ cells) before forming into mature blood cells. Mature blood cells are released from the bone marrow into the bloodstream.
- Lymphocyte white blood cells develop from lymphoid stem cells. There are three types of mature lymphocytes:
- B lymphocytes make antibodies which attack infecting bacteria, viruses, etc.
- T lymphocytes help the B lymphocytes to make antibodies.
- Natural killer cells which also help to protect against infection.
All the other different blood cells (red blood cells, platelets, neutrophils, basophils, eosinophils and monocytes) develop from myeloid stem cells.
You make millions of blood cells every day. Each type of cell has an expected life-span. For example, red blood cells normally last about 120 days. Some white blood cells last just hours or days – some last longer. Every day millions of blood cells die and are broken down at the end of their life-span. There is normally a fine balance between the number of blood cells that you make, and the number that die and are broken down. Various factors help to maintain this balance. For example, certain hormones in the bloodstream and chemicals in the bone marrow called ‘growth factors’ help to regulate the number of blood cells that are made.
The main types of leukaemia are:
- Acute lymphoblastic leukaemia – ‘ALL’.
- Chronic lymphocytic leukaemia – ‘CLL’.
- Acute myeloid leukaemia – ‘AML’.
- Chronic myeloid leukaemia – ‘CML’.
There are various ‘sub-types’ of each of these. In addition there are some other rare types of leukaemia.
- ‘Acute’ means the disease develops and progresses quite quickly.
- ‘Chronic’ means persistent or ongoing. When talking about leukaemia the word chronic also means that the disease develops and progresses slowly (even without treatment).
- ‘Lymphoblastic’ and ‘lymphocytic’ mean that an abnormal cancerous cell is a cell that originated from a lymphoid stem cell.
- ‘Myeloid’ means that an abnormal cancerous cell is a cell that originated from a myeloid stem cell.
The rest of this leaflet is only about acute myeloid leukaemia.
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 sub-types of AML, depending on exactly what cell type becomes cancerous and at what stage in the maturing process. There are eight main sub-types 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 in to a monocyte), and ‘acute myeloid leukaemia 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 gets 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. AML is rare in people under the age of 20. It is slightly more common in men than in women.
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 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 symptoms and problems when acute myeloid leukaemia develops?
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 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 pelvis bone (or sometimes the breast-bone (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 ‘Biopsy – Bone Marrow’ for more detail.)
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 sub-types of AML can be diagnosed by detecting changes which occur to parts of one or more chromosome. (These chromosome changes only occur in the leukaemia cells, not the normal body cells.) It is important to know the exact sub-type 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 wellbeing.
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 drugs 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 sub-types of AML. Research trials continue to try to find even better treatments. The factors which are taken into account include:
- The exact sub-type 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’, ‘standard’ 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 drugs to kill cancer cells, or to stop them from multiplying. See separate leaflet called ‘Chemotherapy’ for further detail.
As many doses of drugs are likely to be given straight into a vein (intravenous) 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. Drugs 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 type of drugs used may be different. This phase of treatment aims to kill any remaining leukaemia cells which may still be present (although 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 drug 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
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 drugs 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 (relapses) 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 drugs used for chemotherapy are powerful and often cause unwanted side-effects. The drugs work by killing cells which are dividing and so some normal cells are damaged too. Side-effects vary from drug to drug and your doctor will advise. The most common side effects are nausea (feeling sick), loss of hair and an increased risk of infection (as the normal white blood cells are affected by treatment). Anti-sickness drugs 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 (prognosis)?
In general, the outlook 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. 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 help and information
Macmillan Cancer Support
Tel: 0808 800 1234 Web: www.macmillan.org.uk
They provide information and support to anyone affected by cancer or leukaemia.
Leukaemia Research Fund
Primarily involved in research and raises funds to these ends. Their website includes a comprehensive range of information for patients about leukaemia.
Tel: 08088 010 444 Web: www.leukaemiacare.org.uk
Aims to promote the welfare of those suffering from leukaemia and allied blood disorders.
References and Disclaimer | Provide feedback
- Milligan DW, Grimwade D, Cullis JO, et al; Guidelines on the management of acute myeloid leukaemia in adults. Br J Haematol. 2006 Nov;135(4):450-74. Epub 2006 Oct 10.
- Estey E; New drugs in acute myeloid leukemia. Semin Oncol. 2008 Aug;35(4):439-48. [abstract]
- Lubbert M, Muller-Tidow C, Hofmann WK, et al; Advances in the treatment of acute myeloid leukemia: from chromosomal aberrations to biologically targeted therapy. J Cell Biochem. 2008 Aug 15;104(6):2059-70. [abstract]