Future Directions In Therapy For Advancedphase

The success of imatinib will clearly result in fewer patients with CML progressing to the advanced phases. Is blastic phase CML a disease of the past? Further observational time will let us know what percent of patients with CML will be cured with imatinib. Although leukemia cells resistant to imatinib have been detected in patients with CML, this has mostly occurred in advanced-phase patients who received imatinib for the first time, having received prior treatment with other agents.47 The incidence of imatinib resistance so far in newly diagnosed chronic-phase patients is still quite low. However, if imatinib resistance is observed, these patients will be at risk for progression to blast-phase disease, and thus future development of therapies in CML will clearly be aimed at preventing the emergence of imatinib-resistant subclones with therapies that may enhance the activity of imatinib48 and/or the use of newer inhibitors with effectiveness in mutated forms of bcr/abl. Initial clinical investigation of these new agents are planned for advanced-phase patients progressing on treatment with imatinib.

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12 Thomas DA: Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood 103(12):4396-4407, 2004.

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14. Avery S: Lymphoid transformation in a CML patient in complete cytogenetic remission following treatment with imatinib. Leuk Res 28(suppl 1):S75-S77,

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