Chronic Myeloid Leukemia (CML) Treatment

Chronic myeloid leukemia is a type of cancer that affects the blood and bone marrow. It occurs when there is an overproduction of abnormal white blood cells, which can crowd out healthy blood cells and interfere with the body’s ability to function properly.

CML typically progresses slowly and is characterised by the presence of the Philadelphia chromosome, a genetic mutation that contributes to the disease's development. Symptoms may include fatigue, weakness, unexplained weight loss, and an enlarged spleen or liver. Diagnosis is usually made through blood tests and bone marrow analysis.

Treatment options for CML often involve targeted therapies that specifically address the genetic mutations associated with the condition, helping to manage symptoms and control the progression of the disease.

The primary cause of chronic myeloid leukaemia is a specific genetic mutation that affects the chromosomes 9 and 22 in blood cells. This mutation leads to the formation of the Philadelphia chromosome, creating a fusion gene known as BCR-ABL.

The BCR-ABL fusion gene produces a protein that promotes the uncontrolled growth of white blood cells, resulting in the overproduction of these abnormal cells. This proliferation can overwhelm the bone marrow, leading to a reduction in healthy blood cells and the symptoms associated with CML.

Exposure to certain risk factors may increase the likelihood of developing blood cancer like chronic myeloid leukaemia. Several factors may increase the risk of developing the disease that include:

• Age: CML is more commonly diagnosed in older adults, particularly those aged 50 to 70.
• Radiation Exposure: Individuals exposed to high levels of radiation, such as those who have undergone radiation therapy for other cancers, may have a higher risk of developing CML.

• Related to Low Haemoglobin (Anaemia): Fatigue, malaise, general weakness
• Symptoms Due to Enlarged Spleen: Pain/dragging sensation in left upper quadrant of abdomen; early satiety
• Due to Low Platelets or Platelet Dysfunction: Bleeding
• Due to Raised Platelets: There could be thrombosis, priapism (males)
• Due to Raised Basophils: Epigastric Discomfort (gastric ulcers)
• In Severe Cases: Fever, bone pains, glandular enlargements all over the body, bleeding

Some patients remain without symptoms and are diagnosed coincidentally when a complete blood count is done as part of a routine health check-up or as part of investigations advised for some other indication.

Diagnosing chronic myeloid leukaemia involves several steps to confirm the presence of the disease and understand its extent. Here’s how the process typically works:

Medical History and Physical Exam

A healthcare provider will begin by discussing any symptoms the patient may be experiencing, such as fatigue or unexplained weight loss. A thorough medical history is taken to identify any previous health issues or family history of blood disorders. During the physical examination, the provider will check for signs such as an enlarged spleen or liver, which can indicate abnormalities in blood cell production.

Blood Tests

Blood samples are collected to evaluate the overall blood cell counts. Specifically, tests will look for an increased number of white blood cells, which is a common indicator of leukaemia. Additionally, the tests may assess levels of red blood cells and platelets, providing a comprehensive overview of the patient’s blood health. Abnormalities in these counts can help guide further testing.

Bone Marrow Evaluation

Bone marrow aspiration is mandatory and involves taking a small sample of bone marrow, usually from the hip bone, using a thin needle. This test is essential for confirming a diagnosis of chronic myeloid leukaemia, as it reveals the cellular changes associated with the disease and helps assess its severity.

Genetic Testing

Laboratory tests are conducted to confirm the presence of the Philadelphia chromosome or the BCR-ABL fusion gene. This genetic testing is crucial, as it provides definitive evidence of chronic myeloid leukaemia. Understanding the specific genetic changes can also help inform treatment options, as targeted therapies are often designed to address these abnormalities. Karyotypic analysis (cytogenetics) is also an essential part of diagnostic work-up.

Imaging Tests

In some cases, imaging tests such as ultrasound or CT scans may be performed. These tests can help visualise any enlargement of the spleen or liver, which can occur in individuals with CML. Imaging provides additional information that may assist in understanding the extent of the disease and any associated complications.

Chronic myeloid leukaemia is typically classified into three distinct phases. Most of the patients are diagnosed in the chronic phase of the disease (CML-CP). The chronic phase is the initial stage of chronic myeloid leukaemia, where the disease is usually detected. During this phase, the number of abnormal white blood cells increases, but symptoms may be mild or absent. Many patients can lead relatively normal lives during this stage. Standard treatments are often effective, and regular monitoring is crucial to track any changes in the condition. Accelerated and blast phases are the phases of disease in progression. With proper treatment, the percentage of CML patients progressing to these phases has reduced from more than 20% to less than 1% to 1.5% per year.

The treatment for chronic myeloid leukaemia focuses on controlling the disease, reducing symptoms, and preventing its progression. Treatment plans are based on the stage of the disease and how well a patient responds to initial therapies. A leading chronic myeloid leukaemia hospital in India can provide comprehensive care to control the disease, reduce symptoms, and enhance the quality of life for patients. Here are the main treatment options:

Targeted Therapy: Frontline Tyrosine kinase inhibitors (TKIs)

These drugs specifically block (target) the activity of the abnormal proteins caused by the Philadelphia chromosome mutation (BCR-ABL gene). The most widely used targeted therapy drugs are tyrosine kinase inhibitors (TKIs). Most patients with chronic myeloid leukaemia can manage their condition long-term with targeted therapy. Approved for frontline treatment are imatinib, nilotinib, dasatinib and bosutinib. In younger patients with high-risk disease and in whom the aim of therapy is to induce a treatment-free remission status, second-generation TKIs may be favored.

Second line treatment: 2nd and 3rd generation TKIs

For CML post failure on frontline therapy, second-line options include second and third generation TKIs.

Salvage therapy: Stem Cell Transplant /non transplant strategies in transplant ineligible patients

Allogeneic stem cell transplantation (also known as bone marrow transplant) remains an important therapeutic option for patients with CML-CP and failure (due to resistance) of at least two TKIs, and for all patients in advanced phase disease. This treatment involves replacing the patient’s diseased bone marrow with healthy donor stem cells. A transplant can potentially cure chronic myeloid leukaemia, but it carries significant risks and requires a compatible donor. making it less common than other treatment options. Older patients who have a cytogenetic relapse post failure on all TKIs can maintain long-term survival if they continue a daily most effective/least toxic TKI, with or without the addition of non-TKI anti-CML agents.

Interferon Therapy

Interferon is a type of immune system therapy that helps the body fight cancer cells. Although less commonly used today due to the success of targeted therapies, interferon therapy may still be considered for patients who cannot tolerate TKIs or in certain special cases.

Chronic myeloid leukaemia can lead to a variety of complications, particularly if the disease progresses or is not adequately managed. Common complications associated with this condition include:

• Enlarged Spleen (Splenomegaly): Chronic myeloid leukaemia can cause the spleen to swell, leading to abdominal discomfort, a feeling of fullness after eating, and difficulty breathing.
• Anemia: Reduced red blood cell production leads to symptoms like fatigue, weakness, and pale skin, sometimes requiring blood transfusions.
• Bone Pain: Leukemia cells can accumulate in the bone marrow, causing persistent bone pain or tenderness, especially in advanced stages.
• Frequent Infections: A weakened immune system makes chronic myeloid leukaemia patients more vulnerable to frequent infections that may require hospitalisation.
• Excessive Bleeding or Bruising: Lower platelet counts result in easy bruising, prolonged bleeding, and, in severe cases, internal bleeding.
• Blast Crisis: In the blast phase, the disease progresses with severe anaemia or low platelet count requiring frequent blood transfusions or life-threatening infections.
• Resistance to Treatment: Over time, chronic myeloid leukaemia patients may become resistant to treatments, necessitating alternative therapies (newer generation TKIs/ allogenic stem cell transplant) and close monitoring.

Consulting with experienced chronic myeloid leukaemia doctors in India can help manage these complications effectively.

Currently, there is no known way to prevent chronic myeloid leukaemia. The disease is primarily caused by a genetic mutation that occurs spontaneously and is not influenced by lifestyle or environmental factors.

1. Can chronic myeloid leukaemia affect fertility?

Yes, chronic myeloid leukaemia and its treatments can affect fertility. Women in reproductive age group on TKI, must be counselled about discontinuing TKI while planning for a child; however this must be done after consulting the haematologists and when the disease is under control.

2. Is chronic myeloid leukaemia hereditary?

No, chronic myeloid leukaemia is not considered hereditary. It is caused by a genetic mutation called the Philadelphia chromosome, but this mutation occurs spontaneously during a person's lifetime and is not passed from parent to child.

3. What is the life expectancy for someone with chronic myeloid leukaemia?

Life expectancy for chronic myeloid leukaemia patients has improved significantly with advancements in treatment, particularly with the use of tyrosine kinase inhibitors (TKIs). Many patients can live near-normal life spans if the disease is managed well. However, this can vary depending on individual response to treatment and the stage at diagnosis.

4. Are there any lifestyle changes recommended after a chronic myeloid leukaemia diagnosis?

After a chronic myeloid leukaemia diagnosis, it’s generally recommended to maintain a healthy lifestyle. This includes eating a balanced diet, getting regular exercise, managing stress, and avoiding smoking or excessive alcohol. These steps can help improve overall well-being and support the immune system during treatment.

5. Can chronic myeloid leukaemia go into remission?

Yes, with effective treatment, chronic myeloid leukaemia can go into remission, meaning the disease is controlled and symptoms disappear.

6. How does chronic myeloid leukaemia affect daily life and activities?

Chronic myeloid leukaemia can impact daily life, especially during the initial stages of diagnosis and treatment. Patients may experience fatigue, reduced energy levels, or side effects from medication. However, with effective management, many people can continue to engage in regular activities and maintain a good quality of life.

Reviewed By Dr Karuna Jha, Consultant - Bone Marrow Transplant, Haemato-Oncology And Haematology on 19 Dec 2024.