| Abstract: |
There has been considerable progress in recent years in the management of malignant disease in general, but in no other area has the progress been quite as remarkable as in the management of chronic myeloid leukemia (CML). The disease move from a status where chemotherapy changed the natural history little if at all to a time when selected patients could be treated and often “cured” by allogeneic stem cell transplantation (allo-SCT).Most recently we have witnessed the introduction of molecularly targeted therapy in the form of imatinib mesylate (IM), which offers the prospect of very substantial prolongation of life for the majority of patients, so much so that it has displaced transplant as primary therapy for newly diagnosed patients. The introduction of IM has changed very fundamentally the approaches to initial management of CML, but has also redirected the search for new agents that may be active in treating and eventually eradicating other forms of malignant disease.The story that has evolved over the last ten or more years has taught us some valuable lessons. First, where the “initiating genetic lesion” in a given neoplasm is reasonably well defined, molecular targeting can be impressively effective.Indeed, the incidence of “acquired” resistance to IM seems to diminish with time. Secondly, CML after its initial stage appears to accrue additional genetic Changes both in the BCR-ABL gene and in other genes in the Ph-positive clone, some of which may be innocuous and others of which may underlie increased resistance to a given agent. This must mean that treatment should be initiated at the earliest opportunity, a conclusion
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