Just to clarify what I may, or may not, have been insinuating...
The classic disease model that most doctors are used to is based on things like bacterial infections. In those cases you have little beasties breeding like mad and mutating as they go. Some are more sensitive to drugs than others. If you give an insufficient treament with the drugs then it comes back and where it comes back from is the most resistant portion of the disease poulation. This automatically means that by mucking about with insufficient treatment you are running a big risk of breeding resistance.
CML is different. The vast majority of the beasties you are zapping are too far down the chain to breed and therefore cannot mutate. The population in which a lasting mutation could occur is only a tiny proportion of the Ph+ cells in your body. This leads to a counter argument that all the mutations must be there to begin with and the 'emergence' of a mutation is just because the drugs knock out the plain vanilla CML lines and the mutants come to dominate.
My personal belief is that the real story has to be somewhere between the two. I entirely buy into the idea that mutations are much more likely to arise in the early, pre-treatment days when there is more reproduction going on in the Ph+ lines. I remain to be convinced of any mechanism that completely stops mutations in the treatement phase - as opposed to just making them less common - and I am not persuaded there is no truth at all in the idea that the more cells the higher the probablilty of something happening. I do however believe, and hope I made this clear, that the probabilities involved are very small indeed.
Bottom line, do I believe that if we had a million people PCRU and half tried stopping treatment and half didn't would we get a handful more progressions in the group who stopped? I think it's possible. But my feeling is that the risk involved is so small you'd probably need a million people to reliably detect it and therefore it is irrelevant to any one individual. As I said, I think the risks invoolved in travelling for the additional tests are probably of the same order as the risks of suspending treatment in these studies.
That is exactly what I have been trying to say. " I entirely buy into the idea that mutations are much more likely to arise in the early, pre-treatment days when there is more reproduction going on in the Ph+ lines. " If you think about it, it really does make sense. Even if you are undetectible, you still have millions of leukemia cells, The TKI only reach the bottom of the chain, In that they only kill the PH+ not the CML stem cell that produces the PH+ and even play with are other blood cells like I had 2 million platelets, I mean that CML stem cell is into everything, even though the red cells and platelets are not nucleus, in and of themselves!! It does not kill the Ancient original CML stem cell at the top that produces this babies or mutations. That is the way I get it!!
As far as most doctor I think they prefer to go by the guidelines mainly to protect themselves and the studies. Perhaps it could take more of their time to monitor, to take TKI holiday breaks or stopping the drug. Then who knows if that will mess your insurance up, they are always looking for ways to get rid of people with pre condition. I had entertained the thought of moving to Fl, My chiropractic said be weary, your insurance rule for Fl may be different then for In. He said I see this happen all the time. It does bother me, because when I changed doctors recently the insurance is giving me fits about paying, even though Indian Univ call and cleared it with my insurance. They got a whole new way they are reading the rule book, suppose I am once again stressing with them, will they pay, I don't know, it is being reprocessed again. Yep they are always looking for away to not pay, if I go off the drugs for awhile and back on I don't know what the Prescription company will come up with. I do remember having this conversation with a Dr. at MD Anderson back in 2006. He said, if I feel the drug was getting me down, with quality of life, or to low counts and toxicity, and I wanted to stop, I could always take the TKI again later. The doctor I go to now, said he does have some patients that stop their drugs usually for about a year then resume. I for one, am happy to stay in a certain range even if it is not undetectable, and that I have for 6 1/2 year, my previous lab in another state, changed their metric scale, The doctor and hospital I go to now, do their own labs and interpretation and I have only had 1 set of labs done, so I will need to do a few PCR/FISH/CBC ETC to establish a baseline in their facility. Again he said I long as I stay in a range he doesn't see the need to go by the guidelines and everyone is an individual. I like feeling better, and I think it would give my organs and body a rest from the toxic drug, even if it was short. Yes it may be a targeted drug, but they do/can cause harm to the body and who knows if there is a point that the harm is irreversible. Like your kidneys shutting down to be on a dialyses. I don't think most doc worry to much about that , because I think they would say, well I would rather not risk your counts going up and go by the guidelines, (perhaps to protect himself) as you can always live on a kidney dialyses. I can remember last year when my son was in ICU with Legionnaire. the doc said these meds are going to shut down his kidneys but )he was on Diaalyses 24/7 for about 6 weeks) we are not worried about his kidneys as he can live on a dialyses for the rest of his life. Fortunately for him he was off the dialyses in about 6 weeks.
And on Gleevec for 6 1/2 years, Just had labs done a couple of weeks ago, no new mutations and I am not undetectable. FISH, found 3 PH+ out of 200 and PCR at 7%, again that was my first labs at the facilitates. The only mutation PH+ I have in 6 1/2 years is the P210. I was very excited when the nurse said all my other labs were normal. I should get them in the mail sometime next week. Again I am happy to stay stable even if only staying in a range, and my CBC and kidney and liver are doing fine. If I were to switch drugs or take a bigger dose I know my other counts would go down, and my life would be miserable. I already have enough health issues just being 64 years, CML, TKI. We are all different I think it is whatever works for the individual and whatever they are comfortable with, however I do think it is important understanding the language. When I mention to the nurse, that my old labs (from NJ) reported the PH+ in B3a2 & B2a2, she said that is more then a doctor cares to know. If found that interesting I am not sure whether or not she understood it, herself. The nurse said she couldn't find my previous labs, I gave them from the lab in NJ. We were talking two different language, but in the end I understood every word she said. She did mention her concern about my FISH, of finding 3 out 200. I told her for 6 1/2 years on my old labs they always report with a range of 92 % normal and 100 % normal and they call two or three PH+ found and recorded as normal. In another words the NJ lab on 2/16/10 reported my fish as 100% normal Nuclei, but below it had picture and said 2 green BCR and two Red Abl, but on 2/22/11 the same lab reported 92.3 % normal with 2 green bcr and 2 red able, so there you go they change their way of report the FISH and the PCR and for 6 1/2 year their is a slight difference in the results, but they stay in a range. I told the nurse I have no mutations, (for 6 1/2 years) and I stay in that range, so I am not concerned. I did say I was having problems with insurance and next Jan I will be Medicare age, so I didn't want to do any switching around now. She said well you are not in any danger. So I sort of got the impress they were pushing changing to Tasigna, which a bit of a different dialogue, then my first consultation with he doctor, which was in the doctors words, "if you stay in a range, no need to change." Hum makes me think sometimes the doc changes his theory/concept, after you become their patient. That has happen to me before, you get an understanding with the doctor, then after you become their patient, a few months down the road, the doc springs on you a whole different theory. Anyhow I not worried at this point. I am sure that my next two FISH / PCR will be within a few number of the first, just like it has for 6 1/2 years, that is all I care about and that my organs are doing fine.
Pam, Sorry that turned out longer then I expected, I am not proof reading this one, I hope it makes sense. There must be other who are thinking a long this line. Also got to keep reminding myself I got to work with the Insurance that is why I would hate to go totally off the drug, insurance always looking for loopholes.