Chronic myeloid leukaemia (CML)

About chronic myeloid leukaemia (CML)

What is CML?

Chronic myeloid leukaemia (CML) is a blood cancer that begins in the bone marrow, where blood cells are made.

In CML, the bone marrow makes too many white blood cells, particularly granulocytes. This is caused by a genetic abnormality called the Philadelphia chromosome. This forms when parts of chromosome 9 and 22 swap places, creating a new gene called BCR-ABL1. This gene makes an enzyme called tyrosine kinase, which normally helps control cell growth.

In CML, this enzyme is always active, causing the bone marrow to make too many abnormal white blood cells. This means there is very little space for normal healthy blood cells. A shortage of red blood cells, platelets and healthy white blood cells can lead to anaemia, bleeding/bruising, and frequent infections.

CML usually develops gradually and progresses slowly over weeks or months. It has three phases:

• Chronic phase
• Accelerated phase
• Blast phase

Who gets CML?

• CML affects around 410 Australians every year
• The average age at diagnosis is 59 years old
• 55% of people diagnosed with CML are 60 years or older

Causes of CML

In most cases, there is no specific cause for the genetic mutation that causes CML. There are some risk factors that increase you risk of developing CML. Such as:

• Age – more common in people over 60 years old
• Gender – more common in males
• Exposure to high dose radiation

Symptoms of CML

Because CML develops slowly, many people don’t have any symptoms (particularly in the early stages), and the disease is picked up on a routine blood test.

Common symptoms of CML include:

Diagnosis of CML

CML is diagnosed through several tests. You may have some or all these tests before an accurate diagnosis can be made.

• Medical history and physical exam
• Blood tests – full blood count (FBC), kidney and liver function, electrolytes
• Genetic tests
• Bone marrow biopsy

Medical history and physical exam 

Your haematologist will check:  

• How you’ve been feeling 
• Your symptoms and how long you’ve been experiencing them 
• Your health history

You will have a physical exam to check for any swelling or pain. Tell your haematologist if you’ve noticed any changes in your body.

Blood tests 

Blood tests are taken:

• At diagnosis (baseline bloods) and throughout treatment.
• To see if CML is affecting your blood cells, electrolytes, or other organs such as the liver or kidneys.  

Once you start treatment. These results are compared with your baseline blood test results to see how you are responding to treatment.

Genetic tests

• Genetic tests look for faults in the cancer cells
• In CML, they are looking for the Philidelphia chromosome and other genetic mutations
• These tests are done from blood and bone marrow samples. You don’t need to do an extra test
• The tests are called: FISH (fluorescence in situ hybridisation) and PCR (polymerase chain reaction)

Bone marrow biopsy 

A bone marrow biopsy confirms the diagnosis of CML and how many blood cells are affected. It is a procedure that involves taking a sample of bone marrow from the hip bone. It is sent to the laboratory for examination under the microscope. The bone marrow biopsy may be done in the haematologist’s rooms, clinic or day procedure center and is usually performed under local anaesthetic. You may also be given a form of pain prevention that you breathe in or some sedation.  

Phases of CML

CML is classified into 3 phases according to the World Health Organization (WHO)

Chronic phase

• The most common phase at diagnosis
• Features a high white blood cell count with only a small number of blast cells (less then 5%)
• If untreated, chronic phase CML will eventually progress to accelerated and/or blast phase
• People usually don’t have many symptoms

Accelerated phase

• Increase in your blast cell count in the blood and bone marrow
• About 5% of patients with chronic phase CML will progress to accelerated phase
• If untreated, accelerated phase CML will eventually transform to blast phase CML
• People will experience some symptoms

Blast phase

• The most aggressive phase
• Significant increase in blast cell count
• CML has spread to tissues and organs
• Blast phase CML can look like acute myeloid leukaemia (AML) or acute lymphoblastic leukaemia (ALL)
• People will experience more symptoms

Prognosis of CML

A prognosis is an estimate your haematologist will make of the likely course and outcome of your disease. You can discuss your prognosis with your haematologist. It is not possible to accurately predict how you will respond to treatment. CML is not curable. However, the disease can be controlled, and most people return to their usual activities.

Treatments for CML

The type of treatment you receive for your CML depends on the phase of the leukaemia. Most people are treated with targeted therapy in the form of an oral tablet. This type of targeted therapy is a cancer growth inhibitor. You may need chemo or a stem cell transplant in combination with targeted therapy, if the leukaemia progresses or doesn’t respond to initial treatment. A clinical trial may also be an option for you. You can explore more information about clinical trials here.

Targeted therapy for CML

Cancer growth inhibitors are a type of targeted therapy that is used to treat cancer:

• They target cell markers or pathways that control how cancer cells grow, divide, and spread
• Specific to a genetic abnormality within the cancer cell. The drug targets that abnormality, also called a cell marker, to stop the cancer cell from growing
• Only affects the cells that have that cell marker

Tyrosine kinase inhibitors (TKI) are targeted therapy used as the primary treatment for CML. Tyrosine kinase is an abnormal protein that is produced by the Philidelphia chromosome. This protein tells leukaemia cells to grow and multiply quickly. TKIs aim to block this protein and stop the leukaemia cells from growing and multiplying.

TKIs:

• Block the tyrosine kinases (proteins) that the cells use to signal each other to grow. This stops the cancer cells growing
• There are several different TKIs that all work slightly differently
• Are all oral tablets
• Must be taken as prescribed; doses should not be missed. Most often taken for life
• Usually work within 3-6 months
• May be switched if the first type doesn’t work well enough or has major side effects

Examples of TKIs used to treat CML are: asciminib, desatinib, imatinib, nilotinib, and ponatinib.

There are some foods and drugs that you should avoid if you’re taking a TKI. They can interact with the drug or how your body absorbs it. You should not eat grapefruit, Seville oranges, pomegranate, star fruit, or licorice. You should not take excessive paracetamol or the herb St John’s Wort.

Side effects of targeted therapies

Side effects from targeted therapies tend to be different from chemo side effects. Side effects of cancer growth inhibitors may include:

• Diarrhoea
• Nausea
• Constipation
• Fatigue
• Shortness of breath
• Feet and hand swelling
• Body aches and pains
• Headache
• Stomach pain
• Rash
• Low blood counts
• Infection
• An irregular heart rhythm called atrial fibrillation
• High blood pressure
• Bleeding
• Hair thinning

More information on targeted therapies can be found on our website: Immunotherapies and targeted therapies.

Follow-up care

You will need regular checkups with your treatment team once you have commenced treatment for your CML. This is to check on how the CML is tracking and any long-lasting side effects from the treatment. If you notice any symptoms of your CML returning after you commence treatment, you should tell your treatment team as soon as possible. You may need tests if you have symptoms to check the leukaemia isn’t progressing. It is possible you may require a change of treatment to keep the leukaemia under control.

Living with CML

How CML affects your everyday life will depend on many factors. It could be that you are returning or managing work, trying to exercise or managing your nutrition. There are some helpful resources and information to guide you – Living well with blood cancer. The Online Blood Cancer Support Service has learn modules on long term side effects, transition to the new normal, cancer related fatigue and more.

Chronic disease management plan

A Chronic Disease Management (CDM) plan is a service provided under Medicare to help you manage long-term health conditions like CML. It’s created with your GP to assist with appropriate support. Regular GP visits under the plan allow for close monitoring of symptoms, medication side effects, or changes in health. The GP can help manage other conditions that may arise or be affected by CML or its treatment (like infections, fatigue, or bone health).

Additionally, a CDM plan means CML patients can access up to 5 Medicare-rebated allied health visits per year. This might include:

• Psychologists – to support mental health and coping with a cancer diagnosis
• Dietitians – to help manage side effects of treatment
• Physiotherapists or exercise physiologists – for fatigue or physical strength

Caring for someone with CML

We have a range of information and resources that may help when you are caring for someone with chronic myeloid leukaemia (CML).

---

References

• Chronic Myeloid Leukemia (CML): Symptoms, Treatment & Prognosis
• Staging & Prognosis for Chronic Myeloid Leukaemia (CML) | Cancer Council NSW
• Signs and Symptoms of CML | American Cancer Society
• Tests for CML | American Cancer Society
• Chronic Myeloid Leukemia Treatment – NCI
• Chronic myeloid leukaemia | eviQ