Chronic Myeloid Leukemia (CML) is a type of cancer that affects the blood-forming cells within the bone marrow. This condition is characterized by the presence of an abnormal chromosome, known as the Philadelphia chromosome, which results from a genetic rearrangement between chromosomes 9 and 22. This rearrangement creates a specific fusion gene, BCR-ABL, which produces a protein that causes immature white blood cells to grow uncontrollably. CML progresses through distinct phases, and understanding these stages is important for managing the disease’s course.
The Phases of Chronic Myeloid Leukemia
Chronic Myeloid Leukemia progresses through three main phases, each with distinct characteristics. The initial and most frequently diagnosed phase is the chronic phase. During this phase, patients may experience mild symptoms, such as fatigue and slight weight loss, or they may be entirely asymptomatic, with the condition often discovered during routine blood tests. In this phase, blast cells, which are immature white blood cells, constitute less than 10% of the cells in the blood or bone marrow.
The disease can then transition into the accelerated phase, where it becomes more aggressive. This phase is indicated by an increase in blast cells, ranging from 10% to 19% in the blood or bone marrow. Other signs of acceleration include a persistent increase in white blood cell counts or spleen size unresponsive to treatment, or new chromosomal abnormalities in CML cells. Patients in this phase experience increased fatigue, fever, and weight loss, and the disease may respond less favorably to standard therapies.
The most advanced and aggressive stage is the blast phase, sometimes referred to as blast crisis. This phase resembles acute leukemia, with 20% or more blast cells in the blood or bone marrow. Large clusters of blasts may be found in the bone marrow, or blasts may spread to tissues outside the bone marrow. Individuals in this phase have severe symptoms, including fatigue, fever, bone pain, and an enlarged spleen, and without intensive intervention, the disease progresses rapidly.
How CML Stages Are Diagnosed and Monitored
Diagnosing CML and determining its phase involves a series of specific laboratory tests. A complete blood count (CBC) is among the first tests performed, as it can reveal a high number of white blood cells, which is characteristic of CML. This initial blood test leads to further investigation.
To assess the bone marrow directly, a bone marrow biopsy and aspiration are conducted. During these procedures, samples of both liquid marrow and a small piece of bone are collected. These samples are then examined under a microscope to identify abnormal cells and determine the percentage of blast cells present, which helps in classifying the disease phase.
Cytogenetic analysis is employed to detect the Philadelphia chromosome. Techniques such as Fluorescence In Situ Hybridization (FISH) identify this specific chromosomal abnormality. This test is important for confirming the diagnosis of CML.
Molecular testing, particularly Polymerase Chain Reaction (PCR), is also performed to detect and quantify the BCR-ABL gene. PCR is highly sensitive, detecting even minute amounts of the BCR-ABL gene, making it valuable for initial diagnosis and ongoing monitoring of treatment response. These tests are used to track the disease’s progression and response to therapy, helping healthcare providers adjust treatment strategies.
Treatment Strategies Based on CML Stage
Treatment approaches for Chronic Myeloid Leukemia are tailored to the specific phase of the disease. For patients in the chronic phase, tyrosine kinase inhibitors (TKIs) serve as the primary treatment. Medications such as imatinib, nilotinib, and dasatinib target the abnormal BCR-ABL protein, blocking uncontrolled CML cell growth. The goal in this phase is to achieve deep molecular remission, enabling many patients to live long, productive lives.
When CML progresses to the accelerated phase, treatment becomes more intensive. This involves increasing the dosage of the current TKI or switching to a different, more potent TKI. If TKI therapy alone is insufficient, additional treatments such as chemotherapy or a stem cell transplant may be considered. The aim is to return the patient to a chronic phase before considering more aggressive options.
The blast phase represents the most advanced stage and requires immediate, aggressive intervention, resembling acute leukemia treatment. This involves intensive chemotherapy, combined with TKIs, to reduce the high number of blast cells. Allogeneic stem cell transplantation, which involves replacing diseased bone marrow with healthy cells from a donor, is considered the most effective curative option for eligible individuals in this phase.
Throughout all phases of CML, supportive care measures are important to manage symptoms and treatment side effects. This can include medications to prevent or treat infections, blood transfusions for low red blood cell or platelet counts, and therapies to alleviate fatigue, pain, or nausea. Psychological and social support, along with lifestyle adjustments like healthy eating and physical activity, also contribute to overall well-being.