Chronic myeloid leukaemia (CML)

Published by Bupa's Health Information Team, December 2010.

This factsheet is for people who have chronic myeloid leukaemia, or who would like information about it.

Chronic leukaemia is a cancer of the blood that develops slowly. Chronic myeloid leukaemia (CML) affects a type of blood cell called myeloid cells and is most common in people aged between 40 and 60.

About chronic myeloid leukaemia

The term leukaemia refers to a group of cancers of the blood cells and bone marrow. If you have leukaemia, your white blood cells become abnormal and divide and grow in an uncontrolled way.

Leukaemia is described as acute (growing rapidly) or chronic (growing slowly). Chronic leukaemia is divided into two main types – CML and chronic lymphocytic leukaemia (CLL). This factsheet focuses on CML.

In CML, cells in your blood known as myeloid cells become cancerous. Myeloid cells are responsible for producing many of the other types of cell in your blood – including red cells, platelets and a type of white blood cell known as granulocytes. In CML, your blood cells, particularly the granulocytes, become abnormal and grow out of control. Because it affects the granulocytes, this condition is also sometimes called chronic granulocytic leukaemia.

In the early stages of the disease, your blood cells may still function reasonably normally. However, if you don’t get effective treatment, the disease can transform into a more malignant condition with more severe symptoms.

About 700 people in the UK are diagnosed with CML each year. It's most common in people aged between 40 and 60 but it can occur at any age. It's very rare in children.

Symptoms of chronic myeloid leukaemia

Symptoms of CML in the early stages of the disease can include:

• feeling generally tired and weak
• weight loss
• high temperature and night sweats
• headaches and vision problems
• discomfort in your abdomen (tummy) due to an enlarged spleen
• gout due to an increased level of uric acid in your blood
• a painful erection in men that won't go down
• itching

You may not have any symptoms at first and many of the symptoms are vague and can be confused with common illnesses like flu. In fact, around one in four people with CML don’t have any symptoms at all but their CML is picked up during a routine blood test.

If you have a more advanced form of CML, you may also notice further symptoms such as:

• feeling extremely tired and breathless
• bleeding or bruising more easily than usual
• a tendency to infections due a reduction of functioning granulocytes in the blood
• pain in your abdomen, caused by an enlarged spleen

These symptoms aren't always due to CML, but if you have them, see your GP.

Causes of chronic myeloid leukaemia

Most people develop CML because an abnormality develops in a chromosome in their myeloid cells. This is called the Philadelphia chromosome. Chromosomes are structures that contain genes – these contain the instructions for life and are inherited from your parents. The Philadelphia chromosome carries an abnormal gene called BCR-ABL. You’re not born with the Philadelphia chromosome but develop it by chance at some point during your life. The reasons why you may develop it are not fully understood, but there seem to be several risk factors. These include:

• exposure to radiation
• age
• being male – you’re slightly more likely to develop CML if you’re a man
• long-term exposure to certain chemicals such as pesticides or benzene, which is found in household paint and solvents
• a weakened immune system – if you have HIV or AIDS, or you’re taking medicines that suppress the immune system, such as chemotherapy medicines
• having ulcerative colitis
• being overweight – if you have a body mass index (BMI) of 30 or above, you’re slightly more likely to develop CML

Diagnosis of chronic myeloid leukaemia

Your GP will ask about your symptoms and examine you. He or she may ask you to have a blood test to check the levels of different cells in your blood. If your GP thinks that you may have CML, he or she will refer you to a specialist called a haematologist (a doctor who specialises in conditions of the blood).

The haematologist will carry out some further investigations to confirm whether you are suffering from leukaemia and if so, whether it is CML. These tests may include:

• a physical examination to check whether your spleen is enlarged
• a bone marrow biopsy – your doctor will remove a sample of your bone marrow, which will be examined under a microscope
• analysis of the chromosomes in the leukaemic cells to identify the Philadelphia chromosome (cytogenetics)
• molecular analysis to identify and quantify the BCR-ABL gene
• further blood tests to check your kidney and liver function
• an ultrasound scan to check if you have an enlarged spleen
• tissue typing – if your doctor thinks that you may need a bone marrow transplant at some stage

These tests are important because they help determine which treatment is best for you.

Staging CML

You may hear your doctors referring to stages of cancer. These stages measure how far your leukaemia has progressed so that you’re provided with the most appropriate treatment.

There are three stages of CML.

• The chronic phase – this is when your symptoms are usually mild. About nine in 10 people with CML are in this phase when they are first diagnosed.
• The accelerated phase – this is when your symptoms become more severe, including losing weight, bruising and having abdominal pain or discomfort.
• The blast phase – this is when the condition develops into an aggressive form of acute leukaemia and you may rapidly become very ill.

Treatment of chronic myeloid leukaemia

Your treatment will depend on the stage of CML and on your general health. It may include a combination of different therapies. If your disease is in the chronic phase, your treatment will be aimed at controlling your symptoms for as long as possible. If you have accelerated or blast phase CML, your treatment will be aimed at reducing your symptoms and putting your leukaemia back into a chronic phase.

Medicines

Your doctor will usually prescribe you a medicine called imatinib to take. Imatinib is a type of medicine called a tyrosine kinase inhibitor. It’s taken by mouth and has few side-effects in most people. Imatinib works by blocking the signals that make the cancer cells grow and multiply, and can get rid of the Philadelphia chromosome from your blood and bone marrow. In many people with CML, it keeps the disease under control for many years.

Imatinib can be used to control your symptoms if you have chronic phase CML. You can also take it if you have accelerated or blast stage CML, as long as you haven’t taken it before. You can continue taking imatinib for as long as it’s controlling your symptoms. Your doctor will monitor you carefully, taking blood tests to check you are still in remission.

If imatinib isn’t working for you or if you’re having severe side-effects, your doctor may suggest taking a newer alternative tyrosine kinase inhibitor, such as dasatinib or nilotinib; however these may not be widely available.

Interferon alpha is another medicine that is used occasionally to treat CML. It can be combined with chemotherapy. Side-effects include headache, fever and depression.

Chemotherapy

You may need to have chemotherapy if you haven’t responded to other treatment. Chemotherapy uses medicines to destroy leukaemic cells in your bone marrow. Chemotherapy for CML is usually with tablets of a medicine called hydroxycarbamide. Hydroxycarbamide is able to fully control chronic phase CML and most people have very few side-effects. However, the drug cannot destroy the Philadelphia chromosome and so the disease can still progress to the accelerated or blast phases.

If you have accelerated or blastic phase CML, you may need to have high-dose chemotherapy. This may involve a combination of drugs, given into your vein.

Bone marrow or stem cell transplant

If you haven’t responded well to other treatments, your doctor may suggest that you have a bone marrow (stem cell) transplant (preferably from a brother or sister) into your body. It can effectively cure CML.

You need to be in general good health to have this treatment.

New treatments

New potential treatments that are being investigated for CML include a chemotherapy medicine called omacetaxine and mini-stem cell transplants. Research is also being carried out on vaccines for CML. Many people with leukaemia take part in clinical trials as treatments are constantly changing. Your doctor can give you more information about clinical trials.

For answers to frequently asked questions on this topic, see Common questions.

For sources and links to further information, see Resources.