Chronic Myeloid Leukaemia

Chronic myeloid leukaemia is a type of blood cancer that develops slowly in the bone marrow, where blood cells are made. Thanks to modern treatments, many people with this condition can now live normal lifespans, as therapy has transformed it from a potentially life-threatening illness into a manageable chronic condition.

Table of contents

• What is chronic myeloid leukaemia?
• What causes this condition?
• Signs and symptoms
• Risk factors
• How is it diagnosed?
• Phases of the disease
• Treatment options
• Outlook and survival
• Living with chronic myeloid leukaemia

Chronic myelogenous leukemia, Chronic granulocytic leukemia, CML

• Bone marrow
• Blood
• Spleen

What is chronic myeloid leukaemia?

Chronic myeloid leukaemia (CML) is a type of blood cancer that starts in the blood-forming myeloid cells or stem cells in your bone marrow. Bone marrow is the spongy tissue inside bones where blood cells are made^[1].

The term “chronic” means this cancer tends to progress more slowly than severe forms of leukaemia. The term “myeloid” refers to the type of cells affected by this cancer^[1]. CML affects both the peripheral blood and the bone marrow^[7].

This condition typically affects older adults and rarely occurs in children, though it can occur at any age^[1]. About 1 in 565 people in the United States will develop the condition. Chronic myeloid leukaemia represents about 15 percent of all types of leukaemia^[2].

CML is one of a group of diseases called myeloproliferative neoplasms, which are disorders where the bone marrow makes too many of certain types of blood cells^[5].

What causes this condition?

People with CML have an acquired genetic change in myeloid stem cells growing in their bone marrow. Acquired mutations are not present at birth and are not something you can inherit. They happen during your lifetime^[2].

Most people with chronic myeloid leukaemia have a gene change called the Philadelphia chromosome. In CML, part of the DNA from one chromosome moves to another chromosome. This change results in the bone marrow making a protein called tyrosine kinase that causes too many stem cells to become white blood cells^[5].

The mutation creates a new fused gene called BCR-ABL. This new gene triggers a chain of events that leads to chronic myeloid leukaemia. The BCR-ABL gene gives new instructions to myeloid stem cells, causing them to make an abnormal version of tyrosine kinase enzymes. These enzymes help manage cell growth and act like “on” and “off” switches. However, the abnormal tyrosine kinase enzymes do not have an “off” switch, so myeloid stem cells in your bone marrow divide and multiply uncontrollably^[2].

Over time, abnormal myeloid stem cells in your bone marrow start making unusually large amounts of immature white blood cells called blasts. Eventually, the blasts accumulate in your bone marrow, making it hard for your bone marrow to make normal red blood cells, white blood cells and platelets. You may have fewer red blood cells but more platelets and abnormal white blood cells^[2].

The Philadelphia chromosome is not passed from parent to child. It happens during your lifetime, and the cause is unknown^[5].

Signs and symptoms

Chronic myeloid leukaemia often does not cause symptoms. It might be detected during a routine blood test. Many people learn they have CML after routine blood test results show unusual blood cell counts^[1][2].

You can have CML without having noticeable symptoms. When symptoms do occur, they are usually mild and get worse over time^[2]. Common symptoms may include:

• Feeling very tired or weak (fatigue)
• Weight loss without trying
• Drenching night sweats
• Fever
• Pain or fullness below the ribs on the left side
• Feeling full after eating a small amount of food
• Loss of appetite
• Bone pain
• Bleeding easily
• Shortness of breath
• Blurry vision caused by bleeding in the back of the eye
• Abdominal swelling or discomfort in the upper left part of your belly, where you can find your spleen

Although CML may present without symptoms, splenomegaly (an enlarged spleen) is the most common finding during physical examination at the time of diagnosis. The spleen may be enormous or only minimally enlarged^[12].

Risk factors

The only known risk factor for CML is exposure to high levels of radiation, and this applies to very few people^[2]. There is an increased incidence of CML among atomic bomb survivors^[7].

We do not know what causes most cases of chronic myeloid leukaemia. The predisposing risk factors are largely unknown^[3][7].

How is it diagnosed?

You usually start by seeing your GP if you have symptoms that could be due to CML. Your doctor may arrange to see you if you have had an abnormal blood test result. They will then decide whether to refer you for further tests or to see a specialist^[3].

Tests and procedures used to diagnose chronic myeloid leukaemia include:

Physical exam: Your healthcare provider examines you and checks vital signs such as pulse and blood pressure. Your provider also feels your lymph nodes, spleen and abdomen for swelling^[16].

Blood tests: A sample of blood is drawn using a needle. The sample is sent to a lab for a complete blood count, also called a CBC. A CBC checks the number of different types of cells in the blood. Chronic myeloid leukaemia often causes a very high number of white blood cells. Blood tests also can measure organ function to show if anything is not working properly^[16].

Bone marrow tests: Bone marrow biopsy and bone marrow aspiration are used to collect bone marrow samples for testing. Bone marrow has a solid and a liquid part. In a bone marrow biopsy, a needle is used to collect a small amount of the solid tissue. In a bone marrow aspiration, a needle is used to draw a sample of the fluid. The samples are typically taken from the hip bone and sent to a lab for testing^[16].

Tests to look for the Philadelphia chromosome: Specialized tests are used to analyze blood or bone marrow samples for the presence of the Philadelphia chromosome or the BCR-ABL gene. These tests may include fluorescence in situ hybridization analysis and other molecular techniques^[16].

Phases of the disease

CML has three phases. The phases are based on how much the CML has grown or spread^[8]. These are chronic, accelerated and blast phases. Knowing the phase helps your doctor decide which treatment you need^[3].

Chronic phase: This is the earliest phase. Most people are diagnosed in the chronic phase. In this phase, CML usually develops very slowly and can be effectively treated. The disease can stay in this phase for many years with treatment^[3][6].

Accelerated phase: Patients with accelerated-phase CML show signs of progression without meeting the criteria for blast crisis. This phase indicates that the disease is getting worse^[12].

Blast phase: This is also called blast crisis. In this phase, CML acts more like an acute leukaemia. The number of blast cells has increased significantly. This is the most advanced and serious phase of CML^[6].

It takes a long time for CML to get worse. You can have this condition for years before noticing symptoms. Transition between the chronic, accelerated, and blast phases may occur gradually over one year or more, or it may occur abruptly^[2][12].

Without treatment, chronic myeloid leukaemia can become a life-threatening illness within three to four years^[2].

Treatment options

Targeted cancer drugs called tyrosine kinase inhibitors (TKIs) are the main treatment for CML^[3][11]. These drugs can change the way that cells work and help the body control the growth of cancer^[14].

Examples of TKI drugs for CML include:

• Imatinib
• Bosutinib
• Dasatinib
• Nilotinib

The main aim of treatment is to control your CML and get you into remission. Remission means there is no sign of active leukaemia in your body, and you do not have any symptoms. This remission can last for years^[14].

Chemotherapy and a stem cell transplant are other possible treatments for CML. It is uncommon to have these as targeted cancer drugs work well at controlling most people’s CML^[14].

Chemotherapy uses anti-cancer drugs to destroy cancer cells. You might have chemotherapy if you have more advanced stages of CML or before a stem cell transplant. CML most commonly transforms into acute myeloid leukaemia (AML), so the chemotherapy treatment you have is the same chemotherapy treatment as AML^[14].

Having a stem cell transplant means destroying as many leukaemia cells as possible and replacing these with healthy stem cells. You first have chemotherapy and other treatments. After the chemotherapy, you have the new stem cells into your bloodstream through a drip. These stem cells make their way to the bone marrow where they make the blood cells you need to recover^[14].

Your healthcare team will develop a plan to monitor how CML responds to treatment. This includes measuring molecular response (based on the number of cells that have the BCR-ABL gene) using a PCR test, and hematologic response (based on the numbers of different types of cells in the blood) using a complete blood count (CBC)^[11].

Outlook and survival

Advances in treatment have improved the prognosis of people with chronic myeloid leukaemia. Most people can achieve remission and live for many years after diagnosis^[1].

Many people with CML may have normal life spans, thanks to therapy that has turned the condition from a life-threatening illness into a chronic illness that medication can manage^[2].

Prompt treatment keeps CML from getting worse. With treatment, CML can stay in the chronic phase for many years^[2][6].

Several factors can affect prognosis, including:

• Age
• The phase of CML
• The presence of the Philadelphia chromosome
• Blood cell counts
• Your overall health and level of fitness
• Whether you have other health conditions

People with CML may develop complications such as anemia (when you do not have enough red blood cells) and an enlarged spleen^[2]. People with CML may also have an increased risk of other types of cancer (second cancers). A recent study showed about 30 percent of people with CML developed second cancers^[2].

Living with chronic myeloid leukaemia

Chronic myeloid leukaemia is often a slowly developing condition. Treatment can keep it under control for many years^[3]. However, living with CML means adjusting to life with a chronic condition.

Many people will need to learn to live with taking daily medicines and the side effects. You will need regular blood tests and hospital visits. Many people face uncertainty and worry about how well treatment is working and what will happen next. With time and support, many people manage to adjust to life with CML^[17].

Emotional support: It can be a huge shock learning that you have a type of cancer. You are likely to feel very uncertain and anxious about the future. You may feel a range of powerful emotions such as feeling shocked, upset, numb, frightened, confused, angry, guilty or sad. Remember that it is natural to experience different feelings when you are coming to terms with your diagnosis^[17].

Daily life: Most people will need to learn to manage daily medicines and side effects. Although some people can eventually stop treatment, for many people there is not an end to the treatment or tests. So you cannot plan for a life after cancer. It can be difficult to adjust to this^[17].

Managing fatigue: Fatigue is a feeling of extreme tiredness that can come on suddenly and leave you feeling completely drained. It is a common symptom of CML and can also be a side effect of your treatment. Evidence shows that regular gentle exercise such as walking can help^[19].

Sun safety: Some drugs used to treat CML are photosensitive. This means that taking them can increase your risk of developing skin cancer, as well as making you more likely to suffer from burns or blisters when you are out in the sun^[19].

Getting support: Try to talk to your friends and family about what is happening and how you feel. This can also help them support you. Get in touch with your doctor or specialist nurse if you are worried about any symptoms. They might be able to reassure you or find out the cause of your symptoms^[17].

You will have regular follow-up visits to check for any signs that the cancer has returned and to manage any side effects of treatment. These visits are an important part of your care^[18].