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Why no PCR tests with these numbers?

I changed oncologists last Summer. August PCR was 55%. He increased Gleevec. October was 29%, he was encouraged. November went to 32% along with significant myelosupression so he took me off Gleevec and ordered mutation testing. It ends up I have a mutation Phe311Leu. He put me on Dasatinib 1/05/19, but my CBC went so low (2/06/19) he took me off that too!  I’m on nothing now at all!   He isn’t familiar with Phe311Leu so he needs to research. Another CBC on 2/14/19 showed better WBC, RBC and platelets, but not good enough yet to start back on TKI he said. I will not see him again till 3/05/19. He has not done a PCR since 11/28/19.  He argues that my CBC tests do not indicate the PCR is needed, just that my bone marrow “needs to come back”. 

i express grave concern with the numbers. He assured me this is “chronic” disease and life long to manage.  But I’m afraid I’m actually Accelerated Phase.  I have asked him to consult with a CML specialist, but (his nurse) says that’s not necessary, he knows what he’s doing.  

 

HI Sarah,

I followed a similar path to you with imatinib not working for me and then switch to Dasatinib and severe myelosuppression followed. I did not have a mutation test, but my doctor felt I had a "variation" that is common in CML (lots of bcr-abl clones) and that he wanted to give dasatinib time to work through a pulsing mechanism.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2503652/

Take a look at table 2 and you will see your mutation listed on the left. Note how dasatnib has a very good impact on it vs imatinib and nilotinib. The odds of dasatinib working for you are high. But first you have to get over the myelosuppression issues and also to make sure you are not in accelerated phase.

What are your blast cell counts? if below 5% or so, you are chronic phase and have time to experiment to get the dose correct and your myelosuppression stabilized. In fact, you have months where you can do this.  If your blast counts are high - that's a different concern.

What my doctor did and I augmented his protocol was to "pulse" my therapy, lowering dose each time. I was never started on 100 mg dasatinib. If you are at that dose it needs to be cut in half the next time you re-start. It is o.k. to go off drug then back on drug while your myelosuppression is being addressed. It is VITAL that you are checked weekly for CBC. Once your neutrophils, platelets or whichever blood cell is suppressed (most likely neutrophils), you have to wait for those counts to recover to near normal. Then you restart dasatinib on the lower dose. One week later, get tested again for blood counts. You don't need a PCR each time. You need a stable blood system. Once you can stay on drug and blood counts are stable and probably rising, that's when you get a new baseline PCR (or FISH if your PCR > 1%). Chances are it will be lower anyway.

I take 20 mg dasatinib and I am PCRU. I want to repeat this. I achieved "undetected" status while only taking 20 mg dasatinib. I was shocked that less was better in my case. My doctor (who is one of four top researchers in the world for CML) explained that dasatinib is a kind of threshold drug. It's very powerful and has a half-life in the blood of only 5 hours. When it works it works. More is not better. More is worse. Key is to find your threshold. Some people need a lot more drug - most don't. In fact, more leads to blood suppression, pleural effusions and immune suppression which can actually counteract the impact. It's not a linear response. The less dasatinib I took, the faster my PCR dropped (along with other reasons). I have no side effects I can feel. I still live with some myelosuppression (red blood cells), my so-called new normal.

Be prudent and pro-active. You will get there. But you need to be sure and get weekly blood tests so you can re-start dasatinib as soon as possible.

This is very helpful info, Scuba, I’m not panicking at least. My last PCR was 11/28/18 at .32 International Standard.  I guess the “Blast” percent is something else (not PCR?). 

Im confused about this. My onc said I’m in chronic, not accelerated, which seemed wrong since other CMLers are saying over 10% PCR is accelerated. 

It does make more sense as you described, that he stopped Dasatinib. It was 100mg and way too hard on bone marrow.  He asked if it came in 50s or 100s tablets; I think he’s considering backing me to 50s.  

Scuba, do you know if it’s okay to split the 100s in half?  

BTW thanks for fast response. I’ve been so nervous and I do feel better. It’s hard to know who to trust. So much confusing info. 

PCR is a measure of bcr-abl activity by CML cells. The more cml cells, the more PCR generally

Blasts are actual cells. There are normal blast cells and leukemic ones. The key is that blast cells normally differentiate into other types of blood cells. In CML they tend to not differentiate and over time accumulate. Accelerated phase has nothing to do with PCR level. One can be over 100% PCR and still be in chronic phase .... which is low blasts. People can live with CML for years without much issue and not know it. It is only when CML transforms into a more dangerous level involving blast cells. This is blast crisis. Blast crisis is what kills in CML.

There is evidence that keeping your vitamin D level up (blood) induces blast cells, even leukemic ones, to differentiate. This can help buy you time as you sort out the myelosuppression issues.