Improved knowledge of the  biology underlying CML has revolutionized the  clinical management of the  disease  and introduced new  therapeutic perspectives. lmatinib a direct Bcr-Abl  kinase  inhibitor leads  to durable cytogenetic remissions and improved survival. However, many patients with CML are slow  responders or develop resistance. Although monitoring is recognized as necessary, when and how to do it and the  proper interpretation of the  results remain in many  ways controversial, and adherence to guidelines deficient. The treatment goals and the  significance of deeper molecular response
 
is still being debated. Second-generation TKis including 2 FDA approved agents are available to overcome Bcr-Abllkinase domain mutations. Even so many patients fail subsequent treatment with these agents, as they can develop highly resistant mutations such as T3151. Newer data on the upfront use of newer second generation TKis is changing the paradigm of CML therapy further and creating the need for newer modalities that can address resistance to these agents. We have also become aware of long-term adverse events of TKI creating a growing interest in treatment discontinuation.

ACCME Accreditation Statement:
This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education through the joint providership of the Medical College of Wisconsin and European School of Hematology. The Medical College of Wisconsin is accredited by the ACCME to provide continuing medical education for physicians.

AMA Credit Designation Statement:
The Medical College of Wisconsin designates this live activity for a maximum of 28.75 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Hours of Participation for Allied Health Care Professionals:
The Medical College of Wisconsin designates this activity for up to 28.75 hours of participation for continuing education for allied health care professionals.