Chronic myeloid leukaemia (CML) is a cancer of blood-forming cells in the bone marrow. Abnormal cells gradually fill the bone marrow and spill into the bloodstream. The disease typically develops very slowly and symptoms such as anaemia, bleeding problems or infections may not occur for years after the disease starts. Treatment aims to reduce the number of abnormal cells.
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 made 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 cells 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 breastbone (sternum), contain the most bone marrow. To make blood cells constantly you need a healthy bone marrow and 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 'pluripotent' 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 lifespan. 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 lifespan. 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 'subtypes' 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 CML. There are other separate leaflets called Leukaemia - a general overview, Acute lymphoblastic leukaemia, Acute myeloid leukaemia and Chronic lymphocytic leukaemia.
What is chronic myeloid leukaemia?
CML is sometimes called chronic myelogenous leukaemia, chronic granulocytic leukaemia, or chronic myelocytic leukaemia.
CML develops due to a problem with a stem cell in the bone marrow, which becomes abnormal. The abnormal stem cell multiplies and the cells that are made from the abnormal stem cells mature and develop into near-normal white cells - mainly neutrophils, basophils and eosinophils (collectively called granulocytes). Large numbers of these cells are made in the bone marrow and spill into the bloodstream.
(In contrast, in acute myeloid leukaemia (AML) the abnormal cells that are made in large quantities are immature abnormal 'blast cells'. This is quite a different disease to CML. (The separate Acute myeloid leukaemia leaflet provides further details.)
Typically, CML develops and progresses slowly - over months or years, even without treatment.
Who gets chronic myeloid leukaemia?
CML is the rarest of the four main types of leukaemia. There are around 750 cases in the UK each year. It occurs mainly in adults and becomes more common with increasing age. The average age at diagnosis is 50 years. It is very rare in children. It is more common in men than in women.
What causes chronic 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 the cell divides, multiplies and dies, are damaged or altered. This makes the cell abnormal. If the abnormal cell survives it may multiply, produce many abnormal cells and develop into a leukaemia. In the case of CML, it is a blood stem cell which is first damaged and affected.
In most cases of CML, the reason why a stem cell becomes abnormal is not known. Research has shown that exposure to electromagnetic fields and living near high-voltage electricity cables do not increase your risk of developing chronic myeloid leukaemia. 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 CML are high-dose radiation (for example, previous radiotherapy for another condition) and exposure to the chemical benzene.
CML is not an inherited condition and does not run in families.
How does chronic myeloid leukaemia develop and what are the symptoms?
Typically, CML runs a course of three phases:
An initial chronic phase
This phase usually lasts a number of years (often five years or more). During this phase the disease progresses very slowly. You may remain stable, with little or no change in the severity of the disease for long periods. Many people in this phase have no symptoms, or only minor symptoms. CML may be first diagnosed by chance in this phase when a blood test is taken for another reason.
The average length of time for this phase is 4-5 years. However, in some people this phase can last for more than 20 years.
In the chronic phase there are 5% or fewer blast cells in the blood and bone marrow.
A transformation phase (also known as the accelerated phase)
In time, the disease process tends to speed up and change. In this phase, the number of abnormal cells in the bone marrow and bloodstream builds up. Many of the abnormal cells are 'blast' (immature) white blood cells. In this phase there are 6-30% blast cells in the blood and bone marrow. As many abnormal cells build up in the bone marrow it is difficult for normal cells in the bone marrow to survive and make enough normal blood cells. Therefore, the main problems and symptoms which tend to develop include:
- Anaemia. This occurs as the number of red blood cells in the bloodstream goes down. This can cause tiredness, breathlessness and other symptoms. You may also look pale.
- Blood clotting problems. This is due to low numbers of platelets in the bloodstream. This can cause easy bruising, bleeding from the gums and other bleeding-related problems.
- Serious infections. The abnormal white blood cells and blast cells do not protect against infection. If there is a reduced number of normal white blood cells which usually combat infection, there is a risk of serious infections developing.
Other symptoms may include: mild pain on the left side of the abdomen caused by a swollen spleen (the spleen may enlarge with abnormal cells), sweats and weight loss.
The transformation phase typically lasts 6-24 months before passing into the third blast phase. Sometimes the chronic phase goes directly into the blast phase with no intermediate transformation phase.
A third 'blast' phase
In this phase the condition rapidly gets worse and behaves like an acute leukaemia. Many immature 'blast' cells develop and fill much of the bone marrow and cause worsening of symptoms described above. Many blast cells spill out into the bloodstream and the blast cell count in blood tests is high. In this phase there are more than 30% blast cells in the blood and bone marrow.
Very rarely, CML develops into a condition called myelofibrosis. This means that the bone marrow can no longer make red cells, white cells or platelets because it is replaced by scar tissue (fibrosis).
How is chronic myeloid leukaemia diagnosed?
A blood test typically shows changes in the number and pattern of white blood cells. This suggests the diagnosis of CML. A bone marrow sample is then usually done to confirm the diagnosis. In the accelerated and blast phase, the number of blast cells seen in the blood sample (the 'blast cell count') also increases.
A bone marrow sample
For this test a needle is inserted into the pelvic bone (or sometimes the breastbone (sternum)). Local anaesthetic is used to numb the area. A small amount of marrow is removed using a syringe. 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 tested in other ways. See separate leaflet called Bone marrow biopsy and aspiration for more detail.
Cell and genetic tests
Detailed tests are done on the abnormal 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.
In most cases of CML the abnormal cells contain a change in chromosome 22. This changed chromosome is shortened and is called the 'Philadelphia chromosome'. An abnormal gene called BCR-ABL is made on the abnormal chromosome 22. This gene is likely to be responsible for the abnormal cancerous behaviour of each abnormal cell. (These chromosome changes only occur in the leukaemia cells, not the normal body cells.) Some rarer subtypes of CML do not have the Philadelphia chromosome.
Various other tests
A chest X-ray, blood tests and other tests may be done to assess your general well-being.
What is the treatment for chronic myeloid leukaemia?
Treatment for the initial chronic phase
The aim of treatment is to control the disease process, to ease any symptoms, and to prevent (or delay) the progression into the further two stages.
You may be advised to have one or more of the the following treatments:
- Imatinib (Glivec®) tablets. This medicine is known as a 'tyrosine kinase inhibitor'. The chemical tyrosine kinase is made by the abnormal gene BCR-ABL on the 'Philadelphia' chromosome described above. This is thought to be responsible for the abnormal growth and behaviour of the abnormal cells. Imatinib works by blocking the effect of tyrosine kinase.
- Interferon alfa. This medicine has been shown to help the immune system to combat leukaemia cells. Interferon alfa is sometimes given, although now imatinib is given much more often.
- Chemotherapy tablets. Chemotherapy is a treatment which uses anti-cancer medicines to kill cancer cells, or to stop them from multiplying. (See separate leaflet called Chemotherapy with cytotoxic medicines for more detail.) Another medicine called arabinoside is also sometimes used to treat CML.
- A stem cell transplant (SCT) - sometimes called a bone marrow transplant - is sometimes an option in younger patients with CML. This may be curative. (See separate leaflet called Stem cell transplant for further detail.)
Treatment for transformation and blast phases
Treatment is usually with more intensive chemotherapy than is given for the chronic phase. This usually means a combination of chemotherapy medicines given directly into a vein (intravenous chemotherapy). Imatinib (Glivec®) tablets may also be used.
Other treatments include antibiotics or antifungal medicines if infection occurs and blood and platelet transfusions to improve low levels of red blood cells and/or platelets.
What is the outlook (prognosis)?
Overall, the outlook is reasonably good. Treatment in most cases is not curative but treatment often keeps the disease under control for a number of years. A successful SCT in people who have this treatment is the only means of a permanent cure.
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. As mentioned above, there are some newer medicines that have been introduced in the last few years that show promise to improve the outlook. 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 (Helpline): 0808 808 0000 Web: www.macmillan.org.uk
Provides information and support to anyone affected by cancer and leukaemia.
Web: http://cancerhelp.cancerresearchuk.org/ provides facts about cancer, including treatment choices.
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.
A website-based support group, published and maintained by CML patients and carers
Tel: 08088 010 444 Web: www.leukaemiacare.org.uk
Aims to promote the welfare of those suffering from leukaemia and allied blood disorders.
Other support groups
See www.patient.co.uk/selfhelp.asp for a list of self-help and support groups for cancer and leukaemia patients.
Further reading & references
- Leukaemia (chronic myeloid) - dasatinib, nilotinib, imatinib; NICE Technology Appraisal Guideline (January 2012)
- Chronic myeloid leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up; European Society for Medical Oncology (2010)
- Leukaemia (chronic myeloid, first line) - dasatinib, nilotinib and standard-dose imatinib; NICE Technology Appraisal Guideline (April 2012)
- Hehlmann R, Hochhaus A, Baccarani M; Chronic myeloid leukaemia. Lancet. 2007 Jul 28;370(9584):342-50.
- Besa E et al, Chronic Myelogenous Leukemia, Medscape, Dec 2011
- Leukaemia (chronic myeloid) - imatinib. NICE Technology appraisal (October 2003)
|Original Author: Dr Tim Kenny||Current Version: Dr Colin Tidy||Peer Reviewer: Dr Helen Huins|
|Last Checked: 19/07/2012||Document ID: 4880 Version: 42||© EMIS|
Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.