Chronic Myeloid Leukemia (CML) is a cancer of the blood and bone marrow characterized by the overproduction of a specific type of white blood cell. This condition features a genetic anomaly known as the Philadelphia chromosome, resulting from a rearrangement between chromosomes 9 and 22. This change creates an abnormal gene, BCR-ABL1, which drives the overproduction of leukemia cells. If not managed effectively, CML progresses from the initial chronic phase to the accelerated phase and then to the more aggressive blast phase.
Defining the Accelerated Phase
The accelerated phase of CML marks a significant progression of the disease, indicating the leukemia is becoming more aggressive. This phase is defined by specific laboratory criteria from organizations like the World Health Organization (WHO), which are based on measurable changes in the blood and bone marrow. A diagnostic marker is the percentage of immature white blood cells, called blasts, rising to 10-19% of the cells in the blood or bone marrow.
Another defining feature is an elevated level of basophils, a different type of white blood cell, constituting 20% or more of the peripheral blood count. Persistently very high or very low platelet counts not caused by treatment can also signal this phase. For example, a platelet count below 100 x 1,000/mm³ unrelated to therapy is one such indicator.
The development of new chromosomal abnormalities in addition to the Philadelphia chromosome, known as clonal evolution, also defines this phase. The appearance of changes like an extra Philadelphia chromosome, trisomy 8, or isochromosome 17q points to genetic instability and disease advancement. These changes confirm the disease is evolving and becoming more complex to manage.
Symptoms and Physical Changes
As CML transitions into the accelerated phase, a person may notice more pronounced physical symptoms. These changes are a direct result of the increasing number of leukemia cells, which grow faster during this stage. Symptoms are often a worsening of milder issues from the chronic phase or the appearance of new ones.
Common experiences include a marked increase in fatigue and weakness. This occurs as cancerous cells crowd out healthy, oxygen-carrying red blood cells in the bone marrow, leading to anemia. Unexplained weight loss and a lack of appetite are also frequently reported, driven by the body’s higher metabolic rate. Some individuals may also develop a persistent low-grade fever or drenching night sweats.
A distinct physical sign is an enlarged spleen, a condition known as splenomegaly. The spleen becomes swollen as it filters excess leukemia cells from the blood, which can cause a sensation of fullness or discomfort in the abdomen. This may lead to early satiety even after eating small amounts. Bone pain can also emerge as the bone marrow becomes packed with leukemia cells.
Treatment Approaches
The primary goal of treatment in the accelerated phase is to return the disease to the more stable chronic phase, requiring more aggressive strategies. Modern CML treatment uses a class of drugs called Tyrosine Kinase Inhibitors (TKIs), which target the BCR-ABL1 protein. If a person’s CML progresses to the accelerated phase while on a TKI, the first step is often to switch to a different, more potent TKI.
For patients diagnosed in the accelerated phase without prior treatment, therapy may start with a second-generation TKI like dasatinib, nilotinib, or bosutinib. Before starting a new TKI, doctors perform a mutation analysis on the BCR-ABL1 gene. This test identifies genetic changes that cause resistance, helping select a more effective drug.
If TKIs are not effective enough or the disease is particularly aggressive, more intensive chemotherapy may be considered to control symptoms or before a stem cell transplant. An allogeneic stem cell transplant, which involves receiving healthy stem cells from a matched donor, is an intensive option. This procedure is considered in the accelerated phase because it offers a potential long-term cure by replacing the cancerous bone marrow, but it carries significant risks and is offered after TKIs have been used to improve blood counts.
Prognosis and Disease Management
The prognosis for individuals with accelerated phase CML is more serious than for those in the chronic phase, but modern treatments have led to significant improvements in outcomes. The immediate objective is to eliminate the signs of the accelerated phase and return the disease to a manageable chronic state. Achieving this goal is a positive indicator for long-term prognosis.
Continuous monitoring is fundamental to managing accelerated phase CML. This involves regular follow-ups with the healthcare team to track treatment response and manage side effects. Blood tests are performed frequently to measure blood cell counts and monitor the levels of the BCR-ABL1 gene using a polymerase chain reaction (PCR) test. This provides a precise measurement of the leukemia’s response to therapy.
The development of TKIs has transformed the outlook for CML, allowing many to live with it as a manageable condition. While the accelerated phase presents greater challenges, the availability of multiple TKIs and the option of a stem cell transplant provide effective tools for physicians. The long-term journey involves a partnership between the patient and their medical team to maintain control over the disease.