By Jason Wasserman MD PhD FRCPC
September 3, 2024
Chronic myeloid leukemia (CML) is a type of cancer that affects the blood and bone marrow. In this disease, the bone marrow, the soft tissue inside your bones where blood cells are made, produces too many white blood cells called myeloid cells. These cells normally help fight infections, but in chronic myeloid leukemia, they grow uncontrollably and do not function properly. Over time, these abnormal cells can crowd out normal blood cells, leading to various health problems.
What are the symptoms of chronic myeloid leukemia?
Many people with chronic myeloid leukemia do not have noticeable symptoms at first. When symptoms do appear, they can include:
- Fatigue: Feeling unusually tired or weak.
- Weight loss: Losing weight without trying.
- Fever: A higher-than-normal body temperature.
- Night sweats: Excessive sweating during the night.
- Abdominal discomfort: Feeling full or having pain in the upper left side of the abdomen, which is where the spleen is located.
These symptoms occur because abnormal white blood cells can build up in the body, enlarging organs like the spleen and preventing normal blood cells from doing their jobs.
What causes chronic myeloid leukemia?
A genetic change in the bone marrow cells causes chronic myeloid leukemia. This change involves two genes, BCR and ABL, which fuse to form an abnormal gene called BCR-ABL. The BCR-ABL gene makes a protein that causes the myeloid cells to grow and divide uncontrollably. This genetic change is not inherited from your parents; it happens during your lifetime and is not passed on to your children.
How is this diagnosis made?
The diagnosis of chronic myeloid leukemia is usually made through blood tests and bone marrow tests. A complete blood count (CBC) often shows an abnormally high number of white blood cells. A bone marrow biopsy may be performed to examine the cells in the bone marrow under a microscope. Additionally, a test called polymerase chain reaction (PCR) can detect the BCR-ABL gene in the blood or bone marrow cells, confirming the diagnosis.
What are the stages of chronic myeloid leukemia?
Chronic myeloid leukemia progresses through different stages, each reflecting the severity and progression of the disease:
- Chronic phase: This is the earliest and most common phase of chronic myeloid leukemia. The disease progresses slowly in this phase, and patients may have mild or no symptoms. The bone marrow shows an increase in mature myeloid cells, which are still somewhat functional. This phase can last for several years with proper treatment.
- Accelerated phase: In the accelerated phase, the disease progresses more rapidly. The number of abnormal cells increases, and these cells start to lose their ability to mature correctly. Patients may begin experiencing more symptoms, such as fatigue, weight loss, or an enlarged spleen. Under the microscope, the bone marrow shows an increased number of immature cells, but not yet as many as in the blast phase. The presence of 10% to 19% blasts in the bone marrow or blood is a key feature of the accelerated phase.
- Blast phase: The blast phase is the most advanced stage of chronic myeloid leukemia, where the disease behaves more like acute leukemia. In this phase, the bone marrow produces a large number of immature white blood cells called blasts. These blasts do not function properly and can crowd out normal blood cells, leading to severe symptoms and complications. More than 20% of blasts in the bone marrow or blood typically indicate that chronic myeloid leukemia has progressed to the blast phase.
These stages help doctors determine the best treatment plan and explain the prognosis. The goal of treatment is often to keep the disease in the chronic phase for as long as possible.
What does chronic myeloid leukemia look like on a peripheral blood smear?
A peripheral blood smear is a test in which a blood sample is spread thinly on a glass slide, stained, and then examined under a microscope. This test allows pathologists to see the different types of cells in the blood and assess their appearance, which is crucial for diagnosing and monitoring chronic myeloid leukemia.
Chronic phase:
- Increased white blood cells: The number of white blood cells (leukocytes), particularly myeloid cells, has significantly increased. These cells include neutrophils, eosinophils, and basophils, all mature white blood cells.
- Left shift: This refers to immature white blood cells, such as myelocytes and promyelocytes, which are normally found in the bone marrow but appear in the blood due to the disease. Despite being immature, these cells are more mature than blasts and still have some functional capacity.
- Basophilia and eosinophilia: There is often an increase in basophils and eosinophils, two white blood cell types usually present in lower numbers.
- Platelets: The number of platelets (tiny blood cells that help with clotting) may be normal or increased, and some platelets may appear larger than normal.
These findings reflect the slow but steady accumulation of abnormal myeloid cells in the blood, characteristic of the chronic phase of the disease.
Blast phase:
- Increased blasts: The number of blasts, which are immature white blood cells, has markedly increased. These cells are larger than normal white blood cells, have a high nuclear-to-cytoplasmic ratio (the nucleus takes up most of the cell), and often have prominent nucleoli (small structures inside the nucleus that are usually visible).
- Anemia: A decrease in the number of red blood cells is often seen, which can cause symptoms like fatigue and pallor.
- Thrombocytopenia: The number of platelets may decrease, leading to an increased risk of bleeding.
- Dysplastic cells: The remaining white blood cells and platelets may appear abnormal (dysplastic), reflecting the disordered cell production in the bone marrow.
These features on a peripheral blood smear indicate that the disease has progressed to the blast phase, which is associated with a poorer prognosis and requires more aggressive treatment.
What does chronic myeloid leukemia look like on a bone marrow biopsy?
When a pathologist examines a bone marrow sample under the microscope, they look for specific features that help diagnose chronic myeloid leukemia and determine its phase:
- Chronic phase: In this phase, the bone marrow shows an increase in mature myeloid cells. These cells appear more abundant than normal, but they still resemble normal white blood cells in shape and size.
- Blast phase: In the blast phase, there is a significant increase in immature cells called blasts. These blasts are larger, have a more irregular shape, and take up more space in the bone marrow. The presence of more than 20% blasts in the bone marrow is a sign that chronic myeloid leukemia has progressed to the blast phase.
What additional tests may be performed to confirm the diagnosis of chronic myeloid leukemia?
In addition to the blood tests and bone marrow biopsy, several other tests may be used to confirm the diagnosis and monitor the progression of chronic myeloid leukemia:
- Cytogenetic analysis: This test examines the chromosomes in the cells to look for the Philadelphia chromosome, which is the chromosome that carries the BCR-ABL gene.
- Fluorescence in situ hybridization (FISH): This test detects the Philadelphia chromosome and is more sensitive than standard cytogenetic analysis.
- Polymerase chain reaction (PCR): PCR is used to detect the BCR-ABL gene and monitor the amount of BCR-ABL over time to assess how well the treatment is working.
What does it mean if the tumour shows high-risk features?
In chronic myeloid leukemia, high-risk features are characteristics that suggest the disease may progress more quickly to the blast phase. These features include:
- A high percentage of blasts in the bone marrow or blood (between 10% and 19%).
- Additional genetic abnormalities in the leukemia cells besides the BCR-ABL gene.
- A very large spleen or very high white blood cell count at diagnosis.
High-risk features indicate that the leukemia is more aggressive and may require more intensive treatment. If these features are present, there is a higher chance that the disease will transition from the chronic phase to the blast phase, associated with a poorer prognosis.
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