5 replies to this topic

[Lbellabliss]

Hi everyone,

I'm reaching out in the hopes that someone has had a similar experience or has some insight on my current situation.

I was diagnosed in June 2013 and originally enrolled in the EPIC trial in which I was assigned to ponatinib. In my original biopsy, all 20 metaphases had the Philadelphia chromosome, but some also had an uncle gene in which the mutation had split twice. Essentially 2 chromosomes on every metaphase. When the trial was ended by the FDA, I had a biopsy in October. I had been on the drug for 3 months and the biopsy showed that although the marrow looked healthy and typically developing, the cytogenetics had showed no progress and still all 20 metaphases had the BCR-ABL split. I went on 100 mg of sprycel and was biopsied again in the end of January. And the biopsy showed the same result. We did multiple mutation testings. But I had none. We bumped my dosing up to 140 mg and I've been on that for 6 weeks. I had another biopsy last week and the results were the same! What is interesting is that in all biopsies the uncle gene is gone. 

I'm so discouraged and disheartened by my body's lack of a full response. My dr is amazing and I'm lucky to have him as he's determined to give me the best treatment. At this point he would like to transplant but we are hesitant as I'm only 24 and I don't want to lose my fertility. It is an option however as my sister is a perfect match thankfully.

He is calling some different colleagues, specialists in cml to get their advice. One guy thought that I should try nilotinib.

Any thoughts, experience, or advice is welcomed! Thank you all!

[Melanie]

So sorry you're having such a difficult time getting your metaphases down, even after attacking it with some very powerful TKI's.  It's no wonder you're so discouraged!  What phase are you in?  Do you still have blast cells? Are your blood counts back to normal?  I'm certainly no doctor, but it may be that you are in a more aggressive phase of the disease and that's why it's being so stubborn.

In my experience, I've also had trouble getting to a negative PH+ cytogenetic test. After 3 years, I still have 2 PH+ chromosomes at my last test. At different times my marrow has shown different mutations, but none have lasted over 6 months except the PH+.  I believe my slow response is more from many breaks and lower dosages from not being able to tolerate the drugs and yours is more from the drugs not being able to get the job done.

Depending on what phase you are in, would determine what your options are. It's really good that your Dr is seeking advice from the experts, as surely they will have an opinion on what your best options are going forward. We're really blessed that there are so many options to try before we're forced to consider transplant, even with your sister being a perfect match. 

Please keep us updated and know that we're here to help and support you. I'm sorry this disease grabbed you at such a young age. Best to you!

[Trey]

Personally I would try every TKI drug available before going to transplant. 

Would you describe the "uncle gene" in more detail.  Was it a doubling of the Philadelphia Chromosome (called amplification) or was it something else?  The term "uncle gene" is not a standard term -- what  did the BMB report call it.  Maybe you could post the exact language of the original BMB report. 

[Antilogical]

Maybe they said "oncogene".

[Lbellabliss]

As I would assume, calling it an 'uncle gene' is just slang. I'm not sure exactly what the scientific term is? I can't find a direct definition for the amplification, but it sounds like that is what is called. Instead of having the single fusion of bcr-abl, there are two fusions of it. Well there was in the first biopsy, now it is gone. So the drug is treating the first one? But not the second? I'm currently traveling for work unfortunately, but I can post the exact biopsy reports when I return this weekend. I also am following up with my doctor tomorrow. Although he's treated a lot of CML patients, he's never seen a situation as this. Hopefully one of his colleges has. I'll post any updates tomorrow after speaking with him as well.

And thank you for your kind words mbrown! I was diagnosed technically in chronic phase, although I was borderline accelerated. Which is also one of the reasons I chose to take part in the ponatinib study in the beginning. My blood counts returned to normal around the end of September which is great and have remained stable. My only abnormality lately is that my platelets are low- most likely a side effect from such a high dose of Sprycel. I haven't received my latest PCR, but 6 weeks ago it was 17%.

Thanks for your replies and advice everyone

[jmoorhou]

Have you checked the CML society to find a specialist in your area.  This is the link:  http://www.nationalc.../meet-our-panel....Would it be possible to preserve sperm cells now for later use.  Gleevec is a  tolerable long term solution and seeing a Naturopath helps with B12 shots etc.

There is also Trey's Log at http://treyscml.blogspot.com/  this has to contain the most information gathered about CML in existence.