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TKI inhibitors have revolutionised CML therapy and the goals for management have shifted from finding newer therapies to optimising existing treatment approaches. We have tried to optimise CML therapy by identifying poor responders early by molecular monitoring, improve adherence by using self reported adherence and optimise intolerance by actively changing TKIs to overcome side effects. BCR-ABL PCR of < 10% at 3 months and < 1% at 6 months have become an accepted standard after the publication by Marin et al. We tried to combine the two measurements and showed that 3 month milestone predicts poor responders and is sufficient to consider changing therapy and that an additional measurement at 6 months does not add any further value. Most existing methods of determining adherence to medications are financially impossible to replicate on a day to day basis or too labour intensive. We tried to measure adherence by 4 different questionnaire based methods (visual adherence scale, Lu's scale, Haynes method and DAMS scale) and correlate it with clinical responses. We have showed that adherence by all methods correlated with clinical responses and Haynes method which quantifies adherence based on number of doses of medications missed over the last 7 days was the best indicator of adherence amongst all. We further looked at the interactions of daily routine, communication with the physician; access to internet and patients views on taking the medications with adherence to therapy and adherence was shown to be influenced by all of them. Majority of the patients on TKI therapy appeared to be anxious and nearly half of them depressed. Patients with a better QOL had improved adherences. We propose a model based on 4 questions with the most significance on multivariate analysis to be possibly used as a surrogate for adherence methods. It has been shown that intolerance affects adherence and hence outcomes. We have tried to improve intolerance by switching TKI therapy in patients who had attained CCyR and with chronic low grade side effects and showed that the side effects improved and all patients had further improvement in the molecular milestones with deepening responses.