Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder resulting from the neoplastic transformation of the primitive hematopoietic stem cell. The disease is monoclonal in origin, affecting myeloid, monocytic, erythroid, megakaryocytic, B-cell, and, sometimes, T-cell lineages. Bone marrow stromal cells are not involved.
CML accounts for 15% of all leukemias in adults. Approximately 8,220 new cases of CML will be diagnosed in 2016, with an estimated 1,070 deaths. The age-adjusted incidence is 1.6 per 100,000 population. With imatinib therapy, the annual mortality has been reduced significantly (to less than 2% to 3% per year, with further mortality reductions after the first 2 to 3 years). This has resulted in an increase in prevalence from approximately 70,000 patients in the US in 2010 to a projected 144,000 in 2030.
The male-to-female ratio is 1.1:1 to 1.4:1.
According to Surveillance, Epidemiology, and End Results (SEER) program and Medical Research Council (MRC) data, the median age of patients with CML is 66 years. However, most patients who are admitted to medical therapy studies are 50 to 60 years old (median: approximately 53 years). Patients in bone marrow transplantation (BMT) studies are usually younger (median age: approximately 40 years).
The cause of CML is unclear. Some associations with genetic and environmental factors have been reported, but in most cases no causative factors can be identified.
There is little evidence linking genetic factors to CML. Offspring of parents with CML do not have a higher incidence of CML than does the general population.
Nuclear and radiation exposures, including therapeutic radiation, have been associated with the development of CML. Exposure to chemicals has not been consistently associated with greater risk.
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.
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.
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.
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.
Historically, patients 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.