Imatinib (STI571) for the Treatment of Chronic Myelogenous Leukemia (CML)
Chronic myelogenous leukemia (CML) is characterized by a reciprocal translocation between long arms of chromosomes 9 and 22 that produces the Philadelphia chromosome. The resulting chimeric BCR-ABL fusion gene is thought to be the molecular cause of the disease. Typical symptom is the marked expansion of myeloid cells that mature normally. The natural history of CML is progression from chronic phase to a rapidly fatal blast crisis within three to five years. Blast crisis is often preceded by an accelerated phase in which increasing doses of initial therapy are required. Treatment options have become more complex in recent years, allogeneic stem cell transplantation is still the only curative option. Recent data show that interferonalpha prolongs life in CML patients, as compared to chemotherapy. New therapies based on the causative molecular abnormality of CML are showing great promise. Imatinib (formerly STI571; Glivec) is an orally administered selective inhibitor of the BCR-ABL tyrosine kinase. Preliminary results from three international phase 11 studies are promising with good hematological and cytogenetical response rates and manageable side effects. Combination with cytostatic drugs may help to overcome the problem of secondary resistance in advanced disease. Longterm observation is required to demonstrate whether imatinib will prolong life in comparison with other methods of treatment.
KeywordsLeukemia Doxorubicine Thrombocytopenia Dermatitis Etoposide
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