Clinical Synopsis

CML occurs with an incidence of 1 to 2 cases per 100,000 population and comprises 15 percent of adult leukemias. Its median age at presentation is 45 to 55 years although some series report a median age of 60 years and older.3 Presently almost half the patients are diagnosed by routine laboratory tests and are asymptomatic at presentation.

CML is typically a triphasic disease. Most patients are diagnosed in the chronic phase. This disease stage is also referred to as indolent or benign and is characterized by excessive proliferation of myeloid progenitor cells in various stages of maturation, their premature release into the peripheral blood, and their tendency to home to extramedullary locations. Despite expansion of the myeloid progenitor stem cell pool, maturation and terminal differentiation of the stem cells are maintained and the disease burden can easily be controlled for months to years by agents such as hydroxyurea and busulfan or other nontoxic therapies. However, after a median interval of 3 to 4 years, CML invariably progresses into an accelerated phase followed after 3 to 12 months by a blastic phase of short duration in which the blast cells have become resistant to most treatments and patients inevitably succumb to their disease. In one-fourth of patients, blast metamorphosis develops without an intervening accelerated course. Whereas definitions of accelerated phase vary, a rapid increase in peripheral blood and/or bone marrow immature myeloid progenitor cells, the presence of extramedullary blastic infiltrates, and the occurrence of additional cytogenetic-molecular markers (clonal evolution) are usually grave signs of disease progression.3,4

The blastic clone expresses lymphoid markers in one-third of the patients and is characterized as myeloblastic or undifferentiated in the remaining two-thirds. Patients whose blasts resemble acute lymphoblastic leukemia (ALL) cells may respond to ALL-type therapy and usually have a better prognosis than patients with acute myeloid or undifferentiated types of leukemia.5

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