Blood cells are formed in the bone marrow, which is a spongy tissue found inside the bones. Blood-forming stem cells divide to produce either more stem cells or immature cells that become mature blood cells over time. A blood stem cell may become a myeloid stem cell or a lymphoid stem cell.
Chronic myeloid leukaemia (CML) affects myeloid-cell-producing stem cells. A myeloid stem cell becomes one of three types of mature blood cells:
- Red blood cells that carry oxygen to all tissues of the body.
- Platelets that form blood clots to stop bleeding.
- Granulocytes (white blood cells) that fight infection and disease.
People with CML produce too many granulocytes. The granulocytes aren’t fully developed and are poorly functioning. Over time, the unhealthy cells accumulate and begin to fill up the bone marrow, preventing it from producing healthy blood cells.
Chronic leukaemia progresses slowly but, although it can be treated, it is not usually possible to cure chronic leukaemia with standard treatments.
Kris is a CML patient. You can watch his story above.
Signs and symptoms of CML
Many patients with CML have no symptoms at the time they are diagnosed. Their CML is discovered following a blood test as part of a routine check-up or for another condition.
There are no specific signs or symptoms which would allow a diagnosis of CML to be made. The most common signs and symptoms are caused by the bone marrow being unable to produce enough normal blood cells.
- Anaemia – due to lack of red blood cells
- Weakness, tiredness, shortness of breath, light-headedness, palpitations
- Infections – due to lack of normal white blood cells
- Infections are more frequent, more severe and last longer
- Fever, malaise (general feeling of illness) and sweats
- Purpura (small bruises in skin), nosebleeds, bleeding gums
- Bleeding and bruising – due to lack of platelets
Other signs and symptoms which may occur include:
- Swollen spleen (in about half of all patients) or less commonly, swollen liver.
CML is often a chance finding during when a blood sample has been taken for another condition or as part of a routine check-up. Most patients with CML will have bone marrow samples taken to confirm the diagnosis and to help to determine exactly what type of leukaemia a patient has.
An important test in CML looks for a specific abnormality in the chromosomes of the CML cells. This is not an inherited genetic abnormality because it is not found in non-leukaemia cells. This is called the Philadelphia chromosome and is formed when chromosome 9 and chromosome 22 swap over part of their DNA. The swap-over forms an abnormal “fusion” gene called BCR-ABL. The BCR-ABL gene is responsible for the abnormal behaviour of CML cells. BCR-ABL is also the target for the newest forms of treatment. Only about 1 in 20 patients with CML does not have the BCR-ABL gene – this is called atypical CML. The amount of the protein produced by the BCR-ABL gene can be measured in the blood and is a very good way to monitor the response to treatment.
Usually, a chest x-ray will be taken and also scans, to look for swollen lymph nodes, or other affected sites. Blood samples will be taken to test for any problems with the liver, kidneys or other organs. Some blood tests and scans will be repeated to check for the response to treatment and any complications. Other tests are usually only done at diagnosis.
Other tests which may be done include:
- X-rays, ultrasound or scans (CT or MRI) – To monitor impact on organs of the body.
Blood tests and bone marrow samples may be repeated during treatment to monitor response.
Staging of CML
There is no staging in CML, unlike in many forms of cancer. This is because CML is spread throughout the body at the time of diagnosis. There are three recognised phases of CML called chronic phase, accelerated phase and blast crisis. Before there were effective treatments almost all patients progressed from chronic to accelerated or blast phase. Modern treatments are very effective at preventing this progression.
There are systems for risk-scoring of CML. These are mainly used in clinical trials and in deciding what treatment to recommend.
Treatment of CML
If you are being treated for any type of leukaemia, you may be asked to consider taking part in a clinical trial. Clinical trials are scientific studies to find the best treatment; you can find more information on our website here.
Almost all patients with CML start treatment immediately after diagnosis. The main exceptions would be very elderly or frail patients who may be too unfit to tolerate treatment.
CML is not considered curable with standard treatments; with the possible exception of stem cell transplants in a small number of younger and/or fitter patients. Even though it is not curable, a new class of drugs called tyrosine kinases (TKIs) have transformed treatment of CML. Most patients with CML can now expect long survival with a good quality of life. There are three TKIs currently used in the UK, imatinib (Glivec®), nilotinib (Tasigna®) and dasatinib (Sprycel®).
The main ways in which CML is treated are:
- Chemotherapy – Cell-killing drugs
- Targeted therapy – Treatments which target a specific weakness of the leukaemia cell – in the case of CML this is the protein produced by the BCR-ABL gene
- Radiation therapy – Usually only used as part of a stem cell transplant
- Stem cell transplant – A small minority of young patients with a very well matched donor may be given a stem cell transplant (bone marrow transplant). This is done using healthy stem cells from a donor
Targeted therapy using TKIs is now the most widely used treatment for CML. This treatment has transformed the outlook for CML patients. Before TKIs were introduced the average survival after diagnosis was about seven years. Now it is expected that many, probably most, CML patients will have a normal or near-normal life-expectancy.
Chemotherapy is the use of cell-killing drugs. These kill the cancer cells and/or stop them from dividing. Chemotherapy is usually given in blocks or ‘cycles’ of treatment. One cycle of treatment will consist of a series of doses of chemotherapy followed by a break for the healthy cells to recover.
Chemotherapy is normally given as a combination of drugs. There are various drugs and combinations which can be used for patients whose CML does not respond to TKIs. Patients will be given a chance to discuss treatment options and detailed information on their treatment plan before it starts. The side effects of treatment vary between different types of treatment and different patients.
Before the introduction of TKIs a stem cell transplant was the preferred treatment for any patient who was fit enough and had a well matched donor. This treatment is now reserved for young fit patients who have a fully matched sibling (brother or sister) who can donate healthy stem cells.
Patients will be given detailed information about any likely side-effects before treatment starts.
Questions to ask your doctor about CML
We understand going through a blood cancer through journey can be difficult. It may help to talk to a close friend or relative about how you are feeling. Here are some questions that may be useful to ask your doctor.
- How would I know if I had CML?
- What tests will I need to have?
- What will the tests show?
- How long will the results take?
- How rare is CML?
- What sort of treatment will I need?
- How long will my treatment last?
- What will the side effects be?
- Is there anything I should or shouldn’t eat?
- Will I be able to go back to work?
- Where can I get help with claiming benefits and grants?
- Where can I get help dealing with my feelings?
We have free patient information available for CML patients.
You can download the booklets on our information pages here.
Alternatively, you can have the information delivered free of charge by requesting it through our resources page.
Support for CML patients
A Facebook group exists called CML UK, for CML patients and carers to chat on an informal basis, ask questions and support each other.
The group has been set up by Nigel Deekes, a CML patients and patient advocate, who found there to be very little support online for CML patients.
The group is a closed group, so content can only be seen by members.
If you would like to join, visit the page and request to join.
There is also a general leukaemia support group on Facebook which is ran by Leukaemia Care. To request to join, click here.
Offline support groups
There area number of CML specific support groups in the UK. Find out more on our support groups page.
CML advocates network
The Chronic Myeloid Leukaemia (CML) Advocates Network is a worldwide network of more than 80 non-profit organisations supporting patients with chronic myeloid leukaemia. It was set up to enable the sharing of best practice and up-to-date information amongst patient advocates across the world.
Other CML charities
CML Support are the UK’s only charity with an exclusive focus on people diagnosed with Ph+ Chronic Myeloid Leukaemia. You can find out more on their website cmlsupport.org.uk
Published date: August 2016
Review date: August 2018