Chronic Myeloid Leukemia (CML) is a cancer of the blood and bone marrow causing an overproduction of white blood cells. A prognosis for CML, which is a forecast of the disease’s likely course, has improved significantly in recent decades. The development of targeted therapies has transformed a once rapidly progressing illness into a manageable condition for most patients.
The Three Phases of CML
The prognosis for CML is determined by its phase at diagnosis, which is a primary factor in the treatment plan. Doctors classify the disease into three phases—chronic, accelerated, and blast—based on the percentage of immature white blood cells (blast cells) in the blood and bone marrow. Each phase represents a different stage of disease progression and carries a different outlook.
Most individuals, around 85-90%, are diagnosed in the chronic phase. This is the earliest stage, where blast cells make up less than 10% of cells in the bone marrow and the leukemia develops slowly. Symptoms are often mild or absent, and the chronic phase responds most effectively to modern treatments.
If untreated, CML can advance to the accelerated phase, where blast cells increase to between 10% and 19% in the bone marrow. The blast phase, or blast crisis, is the most advanced stage. In this phase, blast cells comprise 20% or more of the bone marrow, and the disease behaves like an acute leukemia with a more serious prognosis.
Prognostic Scoring Systems
Beyond the disease phase, doctors use prognostic scoring systems to refine a patient’s outlook and inform treatment decisions. These tools use a combination of factors to calculate a risk score. Three established systems are the Sokal score, the Hasford (or Euro) score, and the EUTOS score.
These scoring systems consider specific biological and clinical markers. Factors include the patient’s age, spleen size, and various blood cell counts. Specifically, they analyze the number of platelets, eosinophils, and basophils, as well as the percentage of blast cells.
The systems generate a score that categorizes CML into a low, intermediate, or high-risk group. For example, the Sokal score uses age, spleen size, platelet count, and blast percentage to assign risk. A lower risk score suggests a more favorable prognosis and can influence the initial choice of therapy.
How Treatment Transforms the Outlook
While prognostic scores are useful, modern treatments have fundamentally altered the outlook for most patients. The introduction of Tyrosine Kinase Inhibitors (TKIs) shifted the goal of CML management from controlling symptoms to achieving long-term remission. This has greatly improved the prognosis for most newly diagnosed patients.
TKIs work by targeting the underlying cause of CML: a genetic abnormality called the Philadelphia chromosome. This chromosome creates the BCR-ABL gene, which produces a protein that signals the bone marrow to make excess white blood cells. TKIs, like the first-generation drug imatinib, block this protein.
This inhibition stops the uncontrolled growth of leukemia cells and allows normal blood cell production to resume. For most individuals diagnosed in the chronic phase, TKI therapy has transformed CML into a manageable chronic condition. While initial risk scores still guide therapy choices, the overall prognosis for patients who respond well to TKIs is very positive.
Monitoring Response to Treatment
A CML prognosis is not static; it is updated based on how well the cancer responds to treatment. Doctors regularly perform tests to measure the effectiveness of TKI therapy. Achieving certain response milestones within specific timeframes is a strong indicator of a favorable long-term outcome.
The first level of response is hematologic. A complete hematologic response (CHR) is achieved when blood cell counts return to normal and no immature cells are visible in the blood. This is the first milestone, with most patients achieving it within three months of starting TKI therapy.
A deeper level of response is cytogenetic, which looks for the Philadelphia chromosome in bone marrow cells. A complete cytogenetic response (CCyR) means no cells with this chromosome are detected in a bone marrow sample.
The most sensitive monitoring is for molecular response, measured by a PCR blood test that detects the BCR-ABL gene. Achieving a major molecular response (MMR) or deep molecular response (DMR) means the gene is at very low or undetectable levels. Attaining a deep and stable molecular response is the goal of CML treatment and is associated with the best long-term prognosis.
Long-Term Outlook and Life Expectancy
For most patients diagnosed in the chronic phase who respond well to TKI therapy, the long-term outlook is positive. Life expectancy for these individuals is now considered normal or near-normal. The disease is managed as a chronic condition, requiring a daily oral medication to keep the leukemia in remission.
This positive outlook has led to a new goal for some: Treatment-Free Remission (TFR), which is the ability to stop TKI medication and remain in remission. TFR is only considered for patients who have been on TKI therapy for several years and have maintained a deep, stable molecular response for at least two years. This process must be done under careful medical supervision.
Studies show that approximately 40-50% of eligible patients who attempt TFR can remain off therapy long-term. For those who see a return of the BCR-ABL gene, restarting TKI therapy is almost always successful at putting the CML back into remission.