There are a number of possible therapeutic strategies for managing the patient who starts treatment with IM at 400 mg/day for CML in CP but then manifests primary or secondary resistance, but currently there is no general consensus. For example, a patient who in the pre-imatinib era would have been considered a candidate for allogeneic stem cell transplant could be offered a transplant after the patient has failed imatinib. Conversely, the patient could be offered treatment with one of the second generation tyrosine kinase inhibitors, namely dasatinib or nilotinib. Patients whose relapse is associated with a substantial sub-clone bearing a T315I mutation will prove resistant to these agents, but may respond to one of the third generation agents that target components of the Bcr-Abl protein other than the ATP-binding domain. Treatment with other agents known to be effective in CML, such as interferon-«, hydroxyurea, or busulfan, is a third option, but clinical results are not likely to be any better than was reported with use of these agents at the end of the last century. Resistant patients who still have low levels of residual disease could be considered for one of the new immunotherapeutic strategies mentioned earlier.
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