Signs and Symptoms

CML usually runs a biphasic or triphasic course. This process includes an initial chronic phase and a terminal blastic phase, which is preceded by an accelerated phase in 60% to 80% of patients.

Chronic Phase

If untreated or treated with drugs that do not significantly affect the Philadelphia-chromosome cells in the marrow, chronic-phase CML is associated with a median survival of 4 to 5 years. During the chronic phase, CML is asymptomatic in 25% to 60% of all cases; in such instances, the disease is usually discovered on a routine blood examination.

In symptomatic patients, the most common presenting signs and symptoms are fatigue, left upper quadrant pain or mass, weight loss, and palpable splenomegaly in 30% to 70% of patients. The liver is enlarged in 10% to 20% of cases. Occasionally, patients with very high white blood cell (WBC) counts especially in the advanced phases of the disease may have manifestations of hyperviscosity, including priapism, tinnitus, stupor, visual changes from retinal hemorrhage, and cerebrovascular accidents.

Patients in chronic-phase CML do not have an increased risk for infection.

Accelerated Phase

This is an ill-defined transitional phase. The criteria used to define accelerated phase in all the studies with interferon and tyrosine kinase inhibitors include the presence of any one of the following factors: blasts > 15%, blasts plus promyelocytes> 30%, basophils > 20%, platelets < 100 × 109/L unrelated to therapy or cytogenetic clonal evolution. Other classifications include more subjective criteria (Table 1) and have not been clinically validated. The classification used may affect the expected outcome for a group of patients defined as being in the accelerated phase. With imatinib therapy, the estimated 4-year survival rate exceeds 50%. The accelerated phase is more frequently symptomatic, and it includes the development of fever, night sweats, weight loss, and progressive splenomegaly.

Blastic Phase

Historically, patients The blastic phase morphologically resembles acute leukemia. Its diagnosis requires the presence of at least 30% blasts in the bone marrow or peripheral blood. The World Health Organization (WHO) has proposed the diagnosis of blast phase if there are at least 20% blasts, but this classification has not been validated, and recent evidence suggests that patients with 20% to 29% blasts have a significantly better prognosis than do those having at least 30% blasts. In some patients, the blastic phase is characterized by extramedullary deposits of leukemic cells, most frequently in the central nervous system (CNS), lymph nodes, skin, or bones.

In the blastic phase usually die within 3 to 6 months. Approximately 70% of blastic phase patients have a myeloid phenotype, 25% have a lymphoid phenotype, and 5% have an undifferentiated phenotype. Prognosis is slightly better for a lymphoid blastic phase than for myeloid or undifferentiated cases (median survival: 9 vs 3 months).

Patients in the blastic phase are more likely to experience symptoms, including weight loss, fever, night sweats, and bone pain. Symptoms of anemia, infectious complications, and bleeding are common. Subcutaneous nodules or hemorrhagic tender skin lesions, lymphadenopathy, and signs of CNS leukemia may also occur.