Beth, we're following your trek through this time of change for you, having good thoughts for your treatment and well being. Great that your office is so very supportive! If you'd like to meet sometime locally (I live in Redwood City), let me know: yaycc@att.net  Chris

The causes of the kinase mutations are not completely understood.  Some think they are there from the beginning, and just show up over the first year or so, and this seems to be the prevailing viewpoint from what I can tell.  As the drugs kill off the non-mutated leukemic cells, only the kinase mutated ones remain.  That is supposedly why most mutations show up within the first year, or else they normally do not occur at all.  This seems to be the case for most of the folks on this Board who have mutations.  So that would mean they do not really "develop" at all, but are simply there from the beginning, or at least the basis of the mutation is there, but takes some time to show up.

Others think that taking a low dosage of drugs might be able to cause mutations.  I asked Dr Druker and Dr Shah about this during an L&LS Education Seminar.  The answer was that they think this is possible, so a low dosage would not be recommended.  But my own personal view is that low dosage mutations do not seem to occur based on observation of folks on this Board and other study of the issue.  But that is not very scientific, so I do not know the right answer.

Most mutations can be overcome by either Sprycel or Tasigna, with a couple exceptions.  Unfortunately, Beth has one of the exceptions.  The odds of having a resistant mutation is low (well under 10%), but that is small consolation to someone who has one.  But several developmental drugs show promise.

I am very interested in this subject of kinase mutations since I would like to use a long term low dosage of Gleevec, since I have been PCRU for 3 years.  I do not see the point of 400mg daily for long term use, and would prefer to drop to 200mg.  But I am just expressing my personal wishes for more information on this issue so dosage options can be more flexible.

So I think there is just not enough information on this issue.  But generally, if a mutation does not occur in the first year, it will likely not show up at all.

Most CML experts would tell you that the quicker and deeper the response to Gleevec, the less chance for mutation.

I also like to remind folks that 95% will do well on CML drugs.  Also, there are now several options for those who get the T315i mutation, whereas just a couple years ago there was only one option -- transplant.

I asked the family about Dawn's case, but did not receive a response, which I can understand the family would like to move on, or maybe they did not know.  Her blog did not reveal the cause of the aggressive course of her disease, so I don't know if she had the T315i.  But it seemed that the chemo she received put her CML into a rage, and also damaged her organs.  Her situation was very unusual because her CML was so aggressive, and it was also very sad to watch through her blog.

http://www.goshdawnit.com/

Good luck, Beth, I'm rooting for you and sending all sorts of positive thoughts your way! Your attitude is so fantastic I'm in awe!

Pat

Trey,

I would be very interested if you contemplate any follow-up action to your speculation about the possibility of dosage reduction from 400mg to 200mg of Gleevac for long term use.

Is this something your onc considers at all feasible or is there just not enough information to yet make such a decision.

It's certainly something on my "side-effects moderating" wish list for daughter Suzie if she can attain and sustain PCRU. (We're currently awaiting her 9 month PCR reading).

Ken Davies.