Chronic Myeloid Leukemia: Symptoms, Causes & Treatment

Chronic myeloid leukemia (CML) is a type of blood cancer that affects myeloid cells. These cells normally develop into red blood cells, platelets, and certain types of white blood cells.

CML is caused by an acquired genetic change in bone marrow cells that leads to the abnormal growth and division of blood cells. It may cause symptoms such as fatigue, unexplained weight loss, bleeding, and bone pain.

Treatment for chronic myeloid leukemia is managed by an oncologist or hematologist and depends on the phase of the disease. Most people are treated with a tyrosine kinase inhibitor, although chemotherapy, radiation therapy, immunotherapy, or a stem cell transplant may be recommended in certain situations.

Main symptoms

The main symptoms of chronic myeloid leukemia include:

• Easy or frequent bleeding

• Fatigue and a general feeling of being unwell

• Fever

• Unexplained weight loss

• Bone pain

• Pain below the ribs on the left side of the abdomen

• Pale skin

• Night sweats

Symptoms of chronic myeloid leukemia usually develop during more advanced stages of the disease.

Anyone with signs or symptoms that may indicate CML should see a healthcare provider for an evaluation. If leukemia is suspected, the person may be referred to a hematologist-oncologist for further testing and diagnosis.

Confirming a diagnosis

Chronic myeloid leukemia is diagnosed by an oncologist or hematologist based on the person’s symptoms, medical history, and physical examination. During the examination, the doctor may feel the lymph nodes, spleen, and abdomen to check for swelling or other abnormalities.

To confirm the diagnosis, the doctor may order a complete blood count (CBC) to measure the levels of white blood cells, red blood cells, and platelets. According to the National Cancer Institute (NCI), genetic testing to identify the Philadelphia chromosome or the BCR::ABL1 gene fusion is an essential part of confirming a diagnosis of chronic myeloid leukemia.

Other tests may include a bone marrow biopsy, bone marrow aspiration, cytogenetic analysis, polymerase chain reaction (PCR) testing, or fluorescence in situ hybridization (FISH). FISH testing is used to look for specific changes in genes and chromosomes within cells.

Phases of chronic myeloid leukemia

Chronic myeloid leukemia is generally divided into the following phases:

1. Chronic phase

Most people are diagnosed during the chronic phase. During this phase, the number of white blood cells is increased, but the person may have no symptoms or only mild symptoms.

Without treatment, chronic-phase CML may progress to a more advanced phase.

2. Accelerated phase

A person may be considered to have accelerated-phase CML when one or more of the following changes are present:

• A persistently high white blood cell count

• Basophils making up 20% or more of the blood

• Very low or very high platelet counts

• New genetic changes in CML cells

People with accelerated-phase CML may experience fever, fatigue, loss of appetite, and weight loss. Without treatment, the disease may progress to the blast phase.

3. Blast phase

The blast phase, also known as blast crisis, is the most advanced phase of CML. During this phase, there is a very high number of immature white blood cells, and platelet levels may also be abnormal.

At this stage, CML behaves similarly to an acute leukemia, such as acute myeloid leukemia. Common symptoms include fever, bone pain, loss of appetite, bleeding, and weight loss.

Possible causes

Chronic myeloid leukemia is not usually inherited. It is caused by an acquired genetic change that develops in the blood-forming cells of the bone marrow.

This change creates a chromosome that is shorter than normal, known as the Philadelphia chromosome. The Philadelphia chromosome is found in the leukemia cells of most people with CML.

The chromosome change produces the BCR::ABL1 fusion gene. This gene makes an abnormal tyrosine kinase protein that promotes the uncontrolled growth and division of blood cells, resulting in cancer.

Factors that may increase the risk of developing chronic myeloid leukemia include older age, male sex, and exposure to high levels of ionizing radiation.

Treatment options

Treatment for chronic myeloid leukemia should be managed by an oncologist or hematologist. The recommended treatment depends on the phase of the disease, the person’s age, overall health, genetic test results, and response to previous treatment.

CML treatment may include tyrosine kinase inhibitors, chemotherapy, immunotherapy, radiation therapy, or a stem cell transplant.

1. Medications

The oral medications most commonly used to treat CML are tyrosine kinase inhibitors, such as imatinib, dasatinib, nilotinib, bosutinib, and ponatinib.

These medications block the activity of the abnormal BCR::ABL1 tyrosine kinase protein. According to the National Comprehensive Cancer Network (NCCN), tyrosine kinase inhibitors are the preferred first-line treatment for most people with newly diagnosed chronic-phase chronic myeloid leukemia.

The specific medication and dose depend on the phase of the disease, previous treatments, genetic test results, and the person’s response to treatment.

2. Chemotherapy

Chemotherapy kills cancer cells or prevents them from growing. It may be given as oral tablets or as an injection into a vein, muscle, or under the skin.

Chemotherapy may be used during the blast phase of chronic myeloid leukemia to help control the disease and return it to the chronic phase. High-dose chemotherapy may also be used to prepare the body for a stem cell transplant.

3. Stem cell transplant

A stem cell transplant replaces diseased blood-forming cells with healthy stem cells. The cells may be collected from the bone marrow, bloodstream, or umbilical cord blood of a compatible donor.

The healthy stem cells are then infused into the bloodstream of the person with chronic myeloid leukemia. These cells travel to the bone marrow and begin producing healthy blood cells.

A stem cell transplant may be considered during any phase of CML. The doctor will determine whether it is appropriate based on the person’s age, overall health, response to other treatments, and the availability of a compatible donor.

4. Bone marrow transplant

A bone marrow transplant is a type of stem cell transplant. Healthy blood-forming stem cells are collected from a donor’s bone marrow and infused into the bloodstream of the person with CML.

The transplanted cells can then settle in the bone marrow and begin producing healthy blood cells.

This treatment is generally considered for people whose disease does not respond adequately to other treatments or continues to progress.

5. Splenectomy

A splenectomy is surgery to remove the spleen. It may be considered when the spleen becomes significantly enlarged and presses against nearby organs.

However, splenectomy is rarely used to treat CML. It is generally considered only when other treatments do not adequately reduce the size of the spleen or relieve related symptoms.

6. Immunotherapy

Immunotherapy helps the immune system recognize and fight cancer cells.

Interferon alfa may be used as immunotherapy for CML in selected cases. However, it is used much less often today because tyrosine kinase inhibitors are generally more effective and better tolerated.

7. Radiation therapy

Radiation therapy uses concentrated radiation to destroy cancer cells or prevent them from growing.

It is rarely used as a primary treatment for chronic myeloid leukemia. However, it may be recommended to reduce the size of an enlarged spleen, relieve bone pain, or help prepare the body for a stem cell transplant.

Is chronic myeloid leukemia curable?

A stem cell transplant is currently the only treatment with the potential to cure chronic myeloid leukemia. However, it is not appropriate for every person and can cause serious complications.

For many people, tyrosine kinase inhibitors can control CML for many years. These medications may reduce the number of leukemia cells to very low or undetectable levels and allow the person to maintain a good quality of life.