In CML (Information to be rechecked in the literature)
-Cytogenetic recovery becomes even more important as it guides
1. quality of response at 3,6,12 months and should be 10, 1 and 0.1% of the quantitative PCR
and failure to do so impact of patient survival
(MR less than 10% at 3 months, linked to 96% survival at 4 years whereas more than MMR>10% at 6 months is linked to 69% survival at 4years!)
2. direct impacting the survival
*Failure to meet that end point, particularly at 3 and 6 months, should prompt Cytogenetic Mutations reevaluation and based on Mutation found pick the right TKI
*T3151---definitely Ponatinib or go to transplant (Allogeneic)
*Y253 and others---Dasatinib
*V299 and others---Nilotinib
*At 6 months, if Molecular response not met,
-check for adherence to treatment by the patient, and check for Mutations (ABL kinase domain point Mutation pattern assessment)
That now Major molecular response (MMR) could be expressed as , or MR 4.5
*Recognition that Frontline treatment is changing to 2nd generation TKI (Dasatinib, Nilotinib) but there is recognition that cardiovascular events are more frequent with these agents ( and Pulmonary Hypertension-particularly with Bosutinib?)
*There is a recording of 4 year survival data (Dasison) MR4.
*Reduction in Ponatinib dosage from 45 to 30mg could reduce lvel of Arterial Thrombosis, and hypertension rates ?without questionable effect on response rate.
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