The detection of KD mutations associated with a rise in the BCR-ABL level. The graphs plot the BCR-ABL levels as measured by RQ-PCR76 in 2 late-chronic-phase patients treated in Australia who achieved a CCyR on imatinib 400 mg/daily. The BCR-ABL levels were calculated according to the proposed international scale (IS). The mutation analysis was performed using a direct sequencing technique.77 The mutation results are depicted as open circles when wild-type BCR-ABL was detected; the amount of shading within the circles indicates the relative size of the mutant sub-clone. Diamonds indicate datapoints. (A) After 18 months on imatinib, the patient had undetectable BCR-ABL that was followed by a rise of at least 5-fold. At that time the D276G mutation was detected. The patient remained on 400 mg imatinib and a CCyR was maintained at 27 months. Thereafter the patient progressed rapidly to lymphoid blast crisis. (B) This patient had a rise of 2.1-fold and the E453G mutation was detected prior to the rise. On the basis of the rising BCR-ABL level and the detection of the mutation the dose of imatinib was increased from 400 to 800 mg per day. The BCR-ABL level subsequently decreased and the CCyR was maintained.
