I would probably repeat all relevant examinations, then switch to nilotinib. Ponatinb can indeed also be considered. SCT is third option, as you suggest

John Goldman













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I believe that in any resistant, and particularly unusual, case, it is very important to know more. More tests require more money, but never as much as a wrong treatment decision. And forgetting money, a wrong treatment decision is not good for the patient. Therefore I confirm that a bone marrow examination, cytology, histopathology, and karyotype, would help. And I confirm that in the meantime I would test again imatinib, full dose.

Regards, Michele Baccarani

A ratio of 432% at baseline is unheard of. I look at it as pretty interesting. I presume that the cABL amplification has been optimum. In my practice I had baselines above 100%, 140%, 125% , even 165% in that range. I explain it by the presence of two bcr-abl1 transcripts per cell. Its like 2 Ph chromosomes in conventional karyotypinf / FISH signals.
Am I right in thinking so !!!! Any other opinions on this.
Regards.
Dr. Deepak K Mishra,
Tata Medical Centre, Kolkata, India.

I agree with Tim about waiting a little longer, but not much longer. If by 3-4 months there is no molecular response, I think the writing is on the wall. Nilotinib post dasatinib in this scenario, is not likely to work and if it does, the response is short-lived at least according to the MDA data. Ponatinib is an option for a quick look to see if there is a response, but in the meantime the option for a RITC allograft should be explored if possible.

Agree with Tim's comments, basically, that it is a bit too early to change the treatment. I’m curious about the methods of the lab where PCR was performed.
A ratio of 432% baseline is uncommon, as it is a ratio of 226% in a patient in CHR. Apart from controlling the molecular response more frequently, every month, why not looking at the karyotype? If you do not want, or cannot, take marrow cells, do FISH on peripheral blood. With a BCR-ABL ratio of more than 100, I’d expect about 100% of nuclei BCR-ABL positive. A word on mutational analysis. Mutations are rare baseline, but this a case of a patient in accelerated phase (basophils more than 20%) who may be worth of a mutational analysis.

Best regards, Michele Baccarani

I would prefer to correlate PCR with FISH results until CCyR is achieved.

Trey
CML Patient Advocate
USA