Chronic Myeloid Leukemia (CML) is a cancer affecting the blood and bone marrow, characterized by the overproduction of certain white blood cells. In contrast, Acute Myeloid Leukemia (AML) is a more aggressive blood and bone marrow cancer. While distinct, CML can transform into AML.
The Phases of CML Progression
Chronic Myeloid Leukemia typically progresses through three distinct phases: chronic, accelerated, and blast crisis. Most individuals are diagnosed in the chronic phase, where symptoms might be minimal or absent, and blast cells constitute less than 10% of the cells in the blood and bone marrow. During this period, the disease is often managed effectively with targeted therapies.
The accelerated phase indicates a worsening of the disease, with blast cells making up 10% to 19% of the cells in the blood or bone marrow. Individuals may start experiencing new or worsening symptoms like fatigue, fever, or weight loss, and the spleen might enlarge. This phase also sees the potential for additional genetic changes within the leukemia cells.
The blast crisis, or blastic phase, is the most aggressive stage. This phase is defined by 20% or more blast cells in the blood or bone marrow. In most cases, this blast crisis manifests as Acute Myeloid Leukemia.
Underlying Reasons for Transformation
The origin of Chronic Myeloid Leukemia lies in a specific genetic abnormality known as the Philadelphia chromosome. This involves a rearrangement between chromosomes 9 and 22, creating a new gene called BCR-ABL. The protein produced by this gene drives the uncontrolled growth of CML cells.
The progression from the chronic phase to the more aggressive accelerated and blast phases, including transformation to AML, involves the accumulation of further genetic changes. Beyond the initial Philadelphia chromosome, additional mutations and chromosomal abnormalities can arise within the leukemia cells. These new genetic alterations provide the cells with characteristics that promote more rapid and uncontrolled proliferation, leading to the acute leukemia-like behavior seen in blast crisis.
Identifying a Transformative Shift
Recognizing a shift from CML to an AML-like state involves observing specific clinical and laboratory changes. A primary indicator is a significant increase in the percentage of immature white blood cells, known as blast cells, in the blood or bone marrow, reaching 20% or more.
Individuals may also experience new or worsening symptoms. These can include unexplained fever, persistent infections, or increased bleeding and bruising due to impaired normal blood cell production. An enlarged spleen, bone pain, and profound fatigue are also signs of disease progression.
Changes in Treatment and Outlook
Once CML transforms into an AML-like blast crisis, the approach to treatment changes significantly. The disease now behaves similarly to acute leukemia, necessitating immediate and more intensive therapeutic interventions. The treatment strategy often shifts from the targeted therapies typically used for chronic phase CML to regimens more commonly employed for AML.
These intensive treatments can include aggressive chemotherapy protocols aimed at reducing the high number of blast cells. In some cases, a stem cell transplant may be considered as a further therapeutic option. The outlook for individuals whose CML has transformed into AML is generally more challenging compared to those remaining in the chronic phase.