Prevention of Resistance in Chronic Myeloid Leukemia: the role of combination therapy

Chronic myeloid leukemia (CML) is a rare disease with a worldwide incidence of approximately 1-2 cases per 100,000 individuals. Chronic myeloid leukemia occurs slightly more frequently in men than in women. The median age at diagnosis is approximately 60 years, and although the incidence increases with age, it also occurs in paediatric patients. Three distinctive phases can be recognized. First, an initial chronic phase that has an average duration of 4 to 6 years without appropriate treatment. During that phase there is a gross expansion of the myeloid compartment, but the cells still retain the capacity to differentiate and function normally. Symptoms in this phase are generally mild; approximately half of the patients have no complaints, and the disease is often discovered by routine blood examination. In general, response to therapy nowadays is very favourable. The next phase is the accelerated phase that has an average duration of approximately 6 months to 1.5 years. The accelerated phase is characterized by the appearance of a certain amount of more immature cells in the blood, complete loss of response to therapy, and the occurrence of constitutional symptoms. The final stage is a transformation to an acute leukemia, the so-called blast crisis, which can be either myeloid or lymphoid in phenotype, in which immature cells (blasts) dominate and survival is measured in weeks to months. Patients with blast crisis have many complaints, and response to treatment is generally very poor.

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