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INCREASED PCR FISH

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My PCR FISH results have climbed to from Undetected last May to 55% in November. I was diagnosed in December, 2020, and have been taking 300MG Gleevec. All blood values have been normal and I'm feeling fine.

Comments, suggestions?

Thank you

PCR and FISH are different tests. If you were "undetected", then I am assuming your result is from PCR and it is now 55%. A FISH test would be in order to verify that you have lost response to Gleevec. Often this is due to a dormant bcr-abl clone which has emerged and for which Gleevec is ineffective.

Assuming your result is real, you will likely need to switch drugs to a TKI which attacks CML differently. Dasatinib is often prescribed when Gleevec has failed. You need to have this done now. 55% is a big jump in such a short time.

Thank you for replying. I am scheduled for a BMB next week because my doctor suspects a mutation. I'll know what the results are a couple of weeks later.
I'm curious, though. If Gleevec has stopped working would not my white blood count be elevated?

A mutation is possible, but I think unlikely. Your Gleevec dose is quite low (at 300 mg) and enabled a pool of resistant cells (the clone) to smolder and emerge once the dominant clone was killed. It is very likely that this new clone will be very sensitive to a new TKI that targets bcr-abl differently (dasatinib, bosutinib). The same thing happened to me when I first started Gleevec and I responded at first and then it failed. I was switched to dasatinib and achieved remission.

Do you know your blast cell count? If it is rising, then you have a problem and need to act more quickly. If blast cell count is less than a few percent or better at zero, you have time.

No surprise your white blood cell count is not elevated. This is the magic of our blood system. Most people don't have symptoms of CML until bcr-abl is at 100% You still have a functional bone marrow (with normal cells at work) which is checking the leukemic cells. Your spleen is likely storing the excess growth. It takes years for CML to finally breakthrough and overwhelm the natural checks and balances and runaway white cell growth takes over. Right now, at 55%, other than with a FISH test or PCR, a CBC (blood count) won't reveal anything abnormal.

Hello,

Thank you for your reply. It answered many of the questions I have about the failure (probably) of my TKI. I've been on 300MG almost since I was diagnosed in December, 2020. The initial dosage of 400 sent my WBC count dangerously low.

What side effects have you experienced with Dasatinib? I was very fortunate taking Gleevec in that I only gained weight and experienced a lot of fatigue. I don't took forward to "breaking in" a new medication especially if it will interfere with other meds I'm taking.

I did not know about the mechanism of CML breaking through and becoming predominate in the blood. Could that explain why I developed the disease a dozen years after forty five post-prostatectomy adjuvant radiation treatments? And, so now, Gleevec is no longer able to contain the proliferation of the leukemia cells thus the elevated BCR-ABL.

I'm quite frustrated by all this. My main concern is that the rising trend of the BCR-ABL wasn't addressed until I brought it up at my doctor's appointment a couple of weeks ago. That seems to go hand-in-hand with my initial diagnosis. In June, 2020, a routine CBC had my WBC at 20,000. The doctor, who I was seeing at the time for anemia said my blood values were normal. I struggled for five months with fatigue

My consultant told me that the weight gain following the early use of the TKI is caused by the body recovering from CML symptoms. I was assured at the time that it was a good thing. Before CML, I was pleased with my weight loss of 3kg: I had not considered that it was caused by illness.