I agree almost completely with your proposal and I would continue the current TKI, monitoring every 3 months for molecular response and every 12 months for cytogenetic response (marrow cell metaphases, because there was a trisomy 8, although trisomy 8 can be seen also by FISH). It is unusual that a patient with stable CCyR does not achieve an MMR, with imatinib, and particularly with second generation TKIs. I understand that he’s compliant, but……..nobody knows! And there may be problems of drug absorption and metabolism. I suggest to contact your Novartis contact to plan a measurement of blood drug concentration. I suggest also to take care of the “cardiovascular” conditions, using the Edinburgh questionnaire for claudicatio, with a periodic evaluation of the ABI, and with an ultrasound evaluation of epiaortic vessels, and of some metabolic indicators like blood glucose, cholesterol and HDL. Best wishes, Michele

. I was referred a male patient. He is 55 now, diagnosed in Sep 2011 with low risk CML ( Sokal and Hasford ). Karyotype showed 9:22 in all and in 2/20 cells an additional trisomy 8 . Started on imatinib and achieved HR and CCR was achieved after 11 months but he never achieved MMR. Despite 6 months of dasatinib and then 4 months of nilotinib still has not achieved MMR but still in hematological remission. The QPCR is stable but transcripts are greater than 1 %. Mutation analysis is negative and he is compliant. Repeat marrow this month is normal with a normal karyotype. Peripheral blood FISH remains negative. His 2 sibs are not HLA matches. Should I look for an unrelated donor ? Is there a role for Bosutinib or Ponatinib ? Patient is obese and a smoker. My general feeling is that I probably would not have switched him from imatinib to begin with, but definitely do not see a role for another switch, either because of expected efficacy and potential for toxicity. I would see if there is an unrelated donor out there in case he loses response, but otherwise would hold tight and monitor carefully. Any other thoughts.