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When CML Experts discuss mutations for certain TKI drugs, do they determine the mutation by a BMB or PCR? The CML EXPERTS must be talking about the mutations at the PH+ level, as TKI do not kill the leukemia stem cell, that created this PH+ mess?


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#1 pamsouth

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Posted 27 December 2011 - 08:20 PM

The web site article is regarding ASH 2011.

http://www.cmladvoca...-on-cml&catid=3

PamSouth


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#2 Trey

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Posted 28 December 2011 - 01:11 PM

Neither.  A special "Kinase Mutation Test" is required.

http://treyscml.blogspot.com/



#3 pamsouth

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Posted 28 December 2011 - 01:53 PM

Thanks Trey,

When I go to my new ONC in January I will know what to ask.  All of these article have been great thoughts to ponder on.  At least the doctor won't have to keep explaining things  over & over to me. Again I will know what questions to ask. 

I am really looking forward to going to my new ONC in Jan.  When I called the LLS they said that IU Simon Cancer Center was the #1 leading cancer center for Indiana. 

I do think my previous ONC is very good as she has many patients who put their lives in her hands and trust her.  But i do think it is important to go to a CML specialist.  I was pretty happy going to her until the mention of changing drugs and I didn't want to go thru that unless I absolutely needed to.  So I thought a second opionion would be good.  Since IU does their labs in house in 48 hours or less, the lab results should be more accurate, then sending the labs out of state.  Otherwise how wold one know to change drugs if the labs are that questionable as to there accuracy and also the lab had changed their method to the IS.

So the new doc said we would do a lab, then wait 3 months, do another lab 3 months later, and one more in another 3 months, then look at the trend over at least a period of 9 months. 

That makes me feel much better and gives me peace of mind as to making a decision of whether or not to change drugs and which one is a better fit for me

Thank for your help.

PamSouth


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#4 rct

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Posted 28 December 2011 - 03:15 PM

48 hours isn't less accurate test results, it is no test results because they can't do them if blood older than 48 hours.

Quarterly PCR is pretty standard unless something is wrong.

Good luck with it.

rct



#5 pamsouth

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Posted 28 December 2011 - 03:23 PM

Thanks RCT for clarifying that for me.

I appreciate all the help I can get.  Sometime I think I know what I am talking about and then learn something new.

Thanks Again,  PamSouth


PamSouth


#6 Fas

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Posted 28 December 2011 - 06:55 PM

Hi Pam,

I found the article a really interesting summary of the current findings of tki therapy, and also an easy read for the lay person.   As one who takes Gleevec and has been doing so for almost 10 years, I found the information on the newer drugs promising.  Think it is amazing that more additional drugs are coming down the pike, especially since CML is a rare form of leukemia.  It is fantastic that the research is beginning to look at stopping the drugs or thinking about identifying maintenance doses that hopefully will reduce side effects and improve quality of life while still keeping the CML in control.  The latter is of great interest to me as I hope to one day either stop Gleevec, but more likely reduce my dose while remaining pcru.  I am cautiously optimistic. 

Pam, I am glad that you sought out another opinion and have found an oncologist that you can partner with in your care.  I think getting second opinions throughout the course of treatment is a good idea.  I have done it.  You will never truly be aware of successes other physicians and their patients maybe having unless you look around.  Good luck with your new doctor and hope things turn out as you want them to. 

Take care,

Fran  



#7 Dina

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Posted 29 December 2011 - 10:07 PM

Thanks for the link, not happy about reading this part though:

"a recent study had revealed that almost all "PCR undetectable patients" were still positive using the more sensitive DNA-based PCR, raising the question that "complete molecular response" may have been a failed promise"

Is this the same PCR test that we have???

Thanks.



#8 pamsouth

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Posted 29 December 2011 - 11:55 PM

Dina,

I think I am reading it the same way you are!!

I do believe that even though the PCR says undetectable, that we still have thousand or maybe even millions of leukemia cells.  All the test; CBC, PCR, (FISH, BMB)  They are only so sensitive.  The labs are only looking at so many cells in a drop of blood, right?  How many pints of blood do we have?  The body makes millions of cells everyday, right?  The leukemia stem cell keeps producing these PH+.  The TKI can only kill so many cells at BCR/ABL level, not the bad stem cell where the leukemia cell starts, that keep producing the PH+ cells.  I think CML is like it says chronic, slow.  So unless they come up with a cure to kill where the bad stem cell, the actually leukemia cell starts, before it makes the Philadelphia chromosome and other blood cells, such as the red cells and platelets. I am thinking as long as we keep the PH+ cell counts down, we can just live with it like diabetes is controlled.

Call Me Lucky had a chart how the chain of events starts from the bone marrow making/ producing the stem cell, then the leukemia cell, then on the myeloid side, the red cell, platelets, white cells. 

I believe the stem cells starts out by producing two side before it makes the blood, the myeloid side and lymphoid side. I believe the lymphoid side make like the white T cells and B cells. 

I can't remember which discussion it was in. 

Hey, Call Me lucky can you produce that graph again?

I think it was Trey that had another link out there on one of discussions on this topic. 

My printer was acting up, so I didn't get the whole link printed.

part of it read as the following;

"The red cells & platelets can have a reduced level of effectiveness because they were produced by the same mutant leukemic ancestor that produced the leukemic WBC.


Unfortunately the TKI drugs cannot shut down the originating leukemic blood stem cells. As a result the leukemic stem cells keep functioning so the TKI drugs must be continued indefinitely to keep killing off the children of those stem cells. The TKI drugs keep the leukemic cells from further mutations, that would lead to accelerated  or blast phase." 

It was a long article, Basically the current goal of our CML drugs is that we are not cured, but can live with the disease in a form that does not harm us.

Well I am still reading the article, if you want to read on, another excerpt;

"Blood cell production has a complex hierarchy with many levels.  It starts with Ancient blood stem cells, which in turn produce long term stem cell, which in turn produce short term stem cell, and finally produce the level of blood cells, which cannot reproduce.  In CML  the original leukemic cell that had the original translocation is near the top of that hierarchy, which means that any cure would require killing off ancient stem cells. But these ancient stem cells have extraordinary means of survival though multiple paths, including BCR/ABL signaling, but also other signaling, methods that get around cml drug impact on BCR/ABL signaling. The originating leukemic cell or cells out-smart the drugs.  They also go dormant for long periods of time by hiding deep in the bone marrow next to the bone, where immune system, cannot find them, and by using other self-survival mechanisms. Where there little oxygen so T-cells and other hunters, and most drugs cannot go. These leukemic cells can sleep for long periods and only come out to reproduce on rare occasions.  When they come out in the open, they presumably become more vulnerable to being spotted as invaders and killed, either by TKI drugs or T-CElls.  Another words the cure will come finding a way to kill the most primitive leukemic stem cell including the mothership cell. We got to  wip out and kill the most primitive leukemic stem cells."

Not just kill at the level of BCR/ABL.  AT LEAST THAT IS THE WAY I GET IT!!

So a cure for CML WILL NEED TO FIND A WAY TO DEFEAT THESE VERY SMART LEUKEMIC STEM CELLS. THESE BLOOD STEM CELLS ARE DIVIDED INTO CATEGORIES SUCH AS CD7, CD34, CD34+, CD38-, ETC. " 

The above is just a few bits and pieces of the article.  I not sure that I can find the link, but I do think that Trey would know.

PamSouth


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