v4n2 - Phases of Disease

Not all patients with CML are similar. Doctors have used a variety of scoring systems to assess the stage and risk of a newly diagnosed CML patients.

CML is somewhat unique among cancers in that it is staged in phases: chronic, accelerated and blast crisis (acute). The Sokal score is the most widely used scoring system and uses a combination of the patient’s age, the size of the spleen, platelet count and the percentage of immature white cells (called blasts) in the peripheral blood to come up with an overall score.

This score is useful in predicting outcome of patients on Gleevec. As many as 91 percent of patients with low-risk Sokal score achieve a complete disappearance of the Philadelphia chromosome-containing cells (complete cytogenetic remission) on Gleevec, compared with only 69 percent of patients with the highest-risk Sokal score.

The phase of CML is based on the percentage of immature blast cells, or myeloid cells, compared with other blood cells in the bone marrow. Patients usually start in the earliest phase of CML (chronic phase) and over time can develop into accelerated phase as well as blast crisis phase. This progression from chronic phase to the more advanced phases is thought to be due to acquisition of newer genetic abnormalities by the CML cell.

In the chronic phase, myeloid blast cells make up less than 5 percent of the blood cells in circulating blood or bone marrow. Approximately 90 percent of people diagnosed with CML are in chronic phase because the disease is usually caught early. Most patients with chronic phase CML may be unaware that they have any problems and may be diagnosed during a routine blood test. An increase in platelets and white blood cells in the bloodstream may be a sign of chronic phase CML.

When the myeloid blast cells reach between 6 percent and 30 percent in the blood or bone marrow, CML enters the accelerated phase. Patients will usually have an enlarged spleen, and fatigue and weight loss become more noticeable.

During the blast crisis phase, the leukemia becomes more aggressive. In the bone marrow and the bloodstream, the myeloid cells make up more than 30 percent of blood cells. Because the myeloid cells crowd out red blood cells and functioning white blood cells, anemia and recurring infections become common. The cancer is hard to treat at this stage and survival is usually three to six months.

Newer ways to predict outcome in CML patients are being developed. Many patients on Gleevec undergo bone marrow biopsies on a regular basis (every six months or so). This allows for detecting the development of new genetic abnormalities in the CML cell that could potentially predict progression from chronic to accelerated phase. If that does happen, patients can potentially switch to one of the investigational drugs for CML or have a bone marrow transplant.