Chronic myeloid leukaemia (CML), also known as chronic myelogenous leukaemia, is a rare type of leukaemia (cancer of blood/blood forming tissue) that causes an overproduction of myeloid cells in the blood. Myeloid cells are responsible for the production of red blood cells, platelets, and all white blood cells except for lymphocytes (one of the main immune cells in the body).
Blood is the bodily fluid of the circulatory system that provides nutrients and oxygen to our tissues, and helps to remove waste from our bodies. There are three primary types of blood cells produced in the inner, spongy portion of the bone (bone marrow) from stem cells (immature blood cells that develop into either red blood cells (RBCs), white blood cells (WBCs), or platelets). RBCs, or erythrocytes, are responsible for providing oxygen to the tissues in our body, as well as transporting carbon dioxide to the lungs to be exhaled. WBCs are responsible for fighting infection and disease in the body. Platelets are blood cells that play a major role in blood clotting (or coagulation), which is an important process that helps reduce blood loss after injury.
CML causes excess blood cells to be produced, which reduces the capacity of the bone marrow to produce healthy RBCs, WBCs, and platelets. Unlike acute myeloid leukaemia (AML), this disease tends to develop slowly over time.
CML is slightly more common in males, and tends to be diagnosed after the age 40 years old. However, anyone can develop this disease.
Treatment
When cancers are detected, they are staged and graded based on size, metastasis (whether the cancer has spread to other parts of the body) and how the cancer cells look under the microscope. Staging and grading helps your doctors determine the best treatment for you.
CML is classified into three groups, which are known as phases instead of stages and grades.
Phases of CML
The three phases of CML are based on how much excess WBCs are found, as well as the accompanying symptoms you are experiencing:
Phase One – Chronic Phase
The first phase of CML is the chronic phase. Most people with CML are diagnosed in this stage, and have few (if any) symptoms. This phase is characterised by an elevated WBC count, and a low quantity of blast (immature) cells found in the blood and/or bone marrow. People in the chronic phase of CML can go several years before being diagnosed, and can have a good prognosis.
If left untreated, the disease can progress to accelerated and/or blast phase of disease.
Phase Two – Accelerated Phase
The second phase of CML is the accelerated phase, which occurs in rare instances. During this phase, CML progresses from a relatively stable disease to a more aggressive one. The accelerated phase is characterised by an increase of blastic cells found in blood and bone marrow, and a higher WBC count than that of the chronic phase. In some cases, patients in this phase may also develop an enlarged spleen. This phase is generally more aggressive, and may not have as good of a prognosis as chronic phase CML.
If left untreated, the disease can progress into the blast phase of disease.
Phase Three – Blast Phase
The third phase of CML is the blast phase, also known as blast crisis, and develops in very rare instances. During this phase, CML progresses rapidly and resembles AML in disease behaviour. The blast phase is characterised by a significant increase of blast cells found in the blood and bone marrow, a very high WBC count, and the development of more severe symptoms. This phase is aggressive, and may not have as good of a prognosis as chronic or accelerated phase CML.
Treatment Options
Once the tumour has been categorised into a phase, your doctor may also recommend genetic testing, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. They will then discuss the most appropriate treatment option for you.
Treatment is dependent on several factors, including age, stage/phase of disease and overall health.
Treatment options for CML may include:
- Targeted therapy, generally including tyrosine kinase inhibitors (TKIs) such as:
- Imatinib.
- Dasatinib.
- Nilotinib.
- Ponatinib.
- Chemotherapy.
- Immunotherapy.
- Stem cell transplants.
- Supportive treatments, potentially including:
- Allopurinol tablets (used to drain excess uric acid caused by elevated WBCs).
- Leukapheresis (a procedure used to quickly reduce dangerous levels of WBCs to a safer level).
- Clinical trials.
- Palliative care.
For more information on the treatment options, please refer to the Rare Cancers Australia treatment options page.
Risk factors
While the cause of CML remains unknown, the following factors may increase the likelihood of developing the disease:
- Genetic mutations – particularly of chromosomes 9 and 22, which can lead to the development of the Philadelphia (Ph) chromosome (causes the production of the enzyme tyrosine kinase, which is thought to be found in many CML patients).
- Exposure to high levels of radiation.
- Exposure to certain industrial chemicals, such as benzene, over a long period of time.
- Previous chemotherapy treatment.
Not everyone with these risk factors will develop the disease, and some people who have the disease may have none of these risk factors. See your general practitioner (GP) if you are concerned.
Early symptoms
People who have chronic phase CML often present with very few (if any) symptoms of disease. As the disease progresses, potentially to the accelerated or blast phase, some of the following symptoms may appear:
- Anaemia, which carries its own set of symptoms:
- Fatigue.
- Dizziness.
- Paleness.
- Shortness of breath.
- Weakness.
- Frequent of persistent infections.
- Easy bruising and/or bleeding.
- Abdominal pain or discomfort, potentially caused by an enlarged spleen.
- Excessive sweating without an apparent cause.
- Unexplained weight loss/loss of appetite.
- Fever.
- Swollen lymph nodes, most commonly in the neck, underarms and/or groin.
Not everyone with the symptoms above will have cancer, but see your GP if you are concerned.
Diagnosis/diagnosing
If your doctor suspects you have a CML, they will order a range of diagnostic tests to confirm the diagnosis, and refer you to a specialist for treatment.
Physical examination
Your doctor will collect your overall medical history, as well as your current symptoms. Following this, they may examine your body to check for any abnormalities.
Blood tests
Blood tests are used to assess overall health and detect any abnormalities. Some of these tests may include:
- General blood test to assess overall health.
- Full blood count, which measures the levels of red blood cells, white blood cells and platelets.
- Blood chemistry and/or blood hormone studies, which analyse the levels of certain hormones and other substances in the blood.
- Blood smears to check changes in the number, type, shape, and size of blood cells for too much iron in RBCs.
Imaging tests
The doctor will take images of your body using magnetic resonance imaging (MRI), a computed tomography scan (CT scan), x-rays, ultrasounds, bone scans and/or positron emission tomography (PET scan), depending on where it is suspected the cancer is. The doctor may also look at other parts of the body and look for signs of metastasis.
Bone Marrow Aspiration & Biopsy
This process involves inserting the needle into the hipbone (or the breastbone in some cases) to remove samples of solid and liquid bone marrow. These samples will then be analysed for abnormalities.
Once the location(s) of the cancer has been identified, the doctor will perform a biopsy to remove a section of tissue using a needle. The tissue sample will then be analysed for cancer cells, as well as the presence of the Philadelphia chromosome. This can be done by a fine needle aspiration (FNA), a core needle biopsy (CNB), or a trephine biopsy (removal of a small portion of bone for analysis).
Prognosis (Certain factors affect the prognosis and treatment options)
While it is not possible to predict the exact course of the disease, your doctor may be able to give you a general idea based on the rate and depth of tumour growth, susceptibility to treatment, age, overall fitness, and medical history. Generally, early-stage CML has a better prognosis and survival rates. However, if the cancer is advanced and has spread, or is found in adulthood, the prognosis may not be as good and there may be a higher risk of cancer recurrence. It is very important to discuss your individual circumstances with your doctor to better understand your prognosis.
References
Some references are to overseas websites. There may be references to drugs and clinical trials that are not available here in Australia.