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Am I losing response?


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#1 Pin

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Posted 13 November 2012 - 10:17 PM

Trey, anyone else - please help me if you can? I am very scared

My history is basically that Gleevec worked very well to begin with (still on 400mg), I had CHR at 10 days (156k wcc at dx).

I had what I would call a pretty slow start and only reached 12% IS at 10 weeks (3 mths), but this may have been testing issues as it seemed to accelerate after that (all IS):

dx = 37% (BM)

3 months = 12% (PB from here on)

6 months = 0.14%

9 months = 0.004%

12 months = 0.0039%

15 months = 0.013%

16 months = 0.03%

As some of you know, I used some herbs to help with my terrible stomach problems at around 11 months (with approval for short-term use only), and continued them until around 14 months. As you can imagine I'm horrified that this may have had a negative impact on my results, especially as this appears to be the exact point that things started going wrong and it would make it all my fault.

Trey, in your opinion and from all of the cases you have seen, does it look like I am losing my response? Is it possible that I need to "wash out" the herbs from my system still - or is that just wishful thinking?

I find it hard to believe that I would get such low results at 9 months, and then jump up a log to "flatline" so I feel the logical conclusion here is that I am steadily increasing - meaning that I likely have a mutation given the early good response. Dan - I know that you mentioned that if there is a mutation, there would be more of a spike in PCR. Can anyone verify if that is really true? Maybe it is simply down to the time of day, or what I have been eating? (I changed from morning to night at around 14 months or so).

I understand that there is a possibility of testing error between 2 points, but it is unlikely between 3 with an almost 1 log increase. I realise that I am still currently MMR, but I really feel by looking at these results, that perhaps it is only a matter of time.

I cannot have a mutation test until I lose my MMR at 0.1%, which does not feel so far away. I am also having another PCR in early December.

If anyone else has had this experience, please share what happened with you? Dan, I know you are going through something similar right now, and I really feel for you. xxx.

Please help!


Diagnosed 9 June 2011, Glivec 400mg June 2011-July 2017, Tasigna 600mg July 2017-present (switched due to intolerable side effects, and desire for future cessation attempt).

Commenced monthly testing when MR4.0 lost during 2012.

 

2017: <0.01, <0.01, 0.005 (200mg Glivec, Adelaide) <0.01, 0.001 (new test sensitivity)

2016: <0.01, <0.01, PCRU, 0.002 (Adelaide)

2015: <0.01, <0.01, <0.01, 0.013

2014: PCRU, <0.01, <0.01, <0.01, <0.01

2013: 0.01, 0.014, 0.016, 0.026, 0.041, <0.01, <0.01 

2012: <0.01, <0.01, 0.013, 0.032, 0.021

2011: 38.00, 12.00, 0.14


#2 TeddyB

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Posted 14 November 2012 - 04:13 AM

Hello Pin, so sorry your going through this.

Which herbs were you using for your stomach issues?

Are you eating something that could interact with the Gleevec on a regular basis?

Changing schedules shouldnt make a difference, but maybe your uptake was better with something you were eating at breakfast?

I know you will get help from the forum experts soon. Until then, check if you are eating or taking anything that is listed here:

http://www.cmlsociet...August 2010.pdf



#3 Sneezy12

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Posted 14 November 2012 - 06:38 AM

Probably a normal bounce at low levels, but I would repeat it in a month. The same thing has happened to me several times. Regards, Frank



#4 Trey

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Posted 14 November 2012 - 10:31 AM

To start with, you are still MMR, so there is no reason to be overly concerned.  Oncs do not get much concerned unless CCyR is lost, and you are still far from that.  There is no way to know what this is (if anything) at this point, so waiting another 3 months for your next test would be advisable.  Mutation testing at these low levels will not work, and it is a low probability that this is caused by one, although not impossible since you are still within the 2 year window since diagnosis. If you want to eliminate the herbs, that is one possibility, or take them several hours apart from the TKI.  Little is known about herb and drug interference with TKI drugs, although interactions are somewhat better defined.

Overall this just looks like what can happen at this point in the PCR cycle (1 -2 year timeframe).  Your response to date indicates a fairly high probability of continued success.  You have previously read my rants about the inaccuracies of PCRs, and what I have read/observed about Australian PCR accuracy is not very impressive  Time will tell, but you have plenty of room on the response scale in case it continues upward. 



#5 LivingWellWithCML

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Posted 14 November 2012 - 07:29 PM

Ping - stay calm!   Yes, I totally understand how you feel right now ... and my worthless left ankle aches for both of us, and I'm not sleeping hardly at all right now, so I'm not very good about staying calm either.  Yet another thing I have to work on.  Anyway...

I haven't gotten my latest PCR test result back yet, but they ran FISH and it was negative, so I'm hopeful that what we're both seeing is just the "constant reminder" that CML is in our bodies ... nothing more, nothing less.  And remember, ~ 0.5 log margin of error in PCR, so it can bounce around quite a bit.

I looked at a blog recently for another CMLer who's going on year 7 or so, and he was keeping a log of PCR results that calmed me down a bit.  I can't remember the specifics, but his ongoing PCR (over several years) ranged between 0.3% and 0.004% IS.  Yes, we all want to be CMR, but this person is perfectly healthy, CCyR and doing fine.

As far as the spike bit, I got that info/guidance from a reliable CML expert ... but honestly I've been so focused on other things that I haven't researched it much further.  If you were seeing my hematologist, he would look at your results and tell you "I'm not concerned, we'll test again in 3 months.  Stay on same dosage."


Dan - Atlanta, GA

CML CP Diagnosed March 2011

Gleevec 400mg


#6 Pin

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Posted 14 November 2012 - 10:02 PM

Thanks everyone, I have a really hard time balancing logic when it comes to my own case - just an anxiety thing I guess, I always jump to the worst case scenario first.

Teddy - thank you for replying, I have checked the charts before but I was on some unusual supplements that weren't listed anywhere (even in the oncology pharmacy). I am really hoping that this will just be a case of "lesson learned" when it comes to drugs/supplements that aren't known about.

Thanks Frank - I truly hope so. I have really had to eat my words about feeling ok about trying herbs that aren't listed because of my good early response. What a mistake that was

Thank you Trey - I really appreciate your input on this, you are always so calm and level-headed about it. I stopped taking the "herbs" at about 13 months (I said 14, but this was wrong). But what I didn't realise was that one of the vitamin supplements I've been taking for cramping may also be interacting (potassium, taurine, glutamine, calcium, vitamin B6, B1, 2, and 3, B12, chromium, folic acid and selenium)? I'm annoyed at my holistic practitioner for being so flippant and pushing me to  be on these things - but really I have no one to blame but myself. I have to be my own advocate, right.

Dan, thank you for your input too, especially about the long-term CMLer, it's always helpful to be reminded that the tests can be so variable and we can still be ok. I'm glad to hear that your FISH is negative, that means still CCyr, right? I hope that you get some peace with your next test - we so sorely need it. This disease (and it's testing!) can be so brutal.


Diagnosed 9 June 2011, Glivec 400mg June 2011-July 2017, Tasigna 600mg July 2017-present (switched due to intolerable side effects, and desire for future cessation attempt).

Commenced monthly testing when MR4.0 lost during 2012.

 

2017: <0.01, <0.01, 0.005 (200mg Glivec, Adelaide) <0.01, 0.001 (new test sensitivity)

2016: <0.01, <0.01, PCRU, 0.002 (Adelaide)

2015: <0.01, <0.01, <0.01, 0.013

2014: PCRU, <0.01, <0.01, <0.01, <0.01

2013: 0.01, 0.014, 0.016, 0.026, 0.041, <0.01, <0.01 

2012: <0.01, <0.01, 0.013, 0.032, 0.021

2011: 38.00, 12.00, 0.14


#7 Tedsey

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Posted 14 November 2012 - 11:45 PM

Pin,

I understand how you feel.  Who wouldn't be "freaked out" by this trend.  You would not be normal if you were not worried.  If it is the beginning of a loss of response, you are still on Gleevec (the ol' first tier drug).  As you know, there are other excellent drugs to try.  So, this is not the "end of the line".  Like others said, it could be the herbs interfering with absorption or just the often undependable, but so important PCR, the only thing we have to depend on.  What an irony.  As agonizing as it is to wait another 3 months, it is 3 more months until we really have to worry about it, (I also had a pretty large uptick and had to wait it out--it was tough, but my PCR eventually went down again).  The reality is, although is seems to be rare before being somewhat forewarned by a PCR value, progression can happen pretty much  at any time.  We are always at the mercy of the disease and the drugs  that try to control the rogue protein it creates.  It is enough to drive  you crazy if you think about it too much, which I do.  It totally  sucks.  So how do we live well with this?  Thank goodness we have each other and the LLS. 

I am sorry you have such tummy troubles.  It is hard to live with.  I hope you find a successful way to feel better.  So, I just got my latest PCR back.  I have now flat-lined for the last 12 months (not an increase, but unsettling).  I have been taking Sprycel, 100mg, for over 2 years, (never missed a TKI pill, ever--I swear to God), and I have only had a CCyR.  Basically, I am already at the top of the TKI hierarchy.  But, there is still hope for continued MMR for you.  I failed Gleevec at 9 months.  So, if you eventually need to change drugs, you have had a good go with the one that is tried and true (Gleevec).  Whatever happens, I wish only good things for you.  Don't lose hope.  Even I haven't.  A flat line also means no progression, at least, not yet.  And and there is always the herb thing to sort out as reason for your increase. 

Nevertheless, we both just got 3 more months, of course, never without a little anxiety or worries, you know, "strings attached", but try to live this time as well as you can.  I'm gonna try to do the same.  May this just be a bump in the road to complete healing.

Keeping high hopes and fingers crossed for you,

Tedsey  



#8 Pin

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Posted 15 November 2012 - 05:56 PM

Tedsey, thank you so much - your reply came at another feeling very low moment for me and it helped me a lot. I am both simultaneously glad and sad that your latest test came in as stable. When we are stable, we'd give anything to be trending down, and when we are going up, we'd do anything to be stable again! But I heard you say recently that you were feeling quite well at the moment - this is really good to hear as I know you have had your share of feeling crappy. All the best Pin xxx.


Diagnosed 9 June 2011, Glivec 400mg June 2011-July 2017, Tasigna 600mg July 2017-present (switched due to intolerable side effects, and desire for future cessation attempt).

Commenced monthly testing when MR4.0 lost during 2012.

 

2017: <0.01, <0.01, 0.005 (200mg Glivec, Adelaide) <0.01, 0.001 (new test sensitivity)

2016: <0.01, <0.01, PCRU, 0.002 (Adelaide)

2015: <0.01, <0.01, <0.01, 0.013

2014: PCRU, <0.01, <0.01, <0.01, <0.01

2013: 0.01, 0.014, 0.016, 0.026, 0.041, <0.01, <0.01 

2012: <0.01, <0.01, 0.013, 0.032, 0.021

2011: 38.00, 12.00, 0.14


#9 LivingWellWithCML

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Posted 15 November 2012 - 06:58 PM

Hey Pin,

I just got my PCR result and it is almost the same result - 0.125% vs. 0.124% 6 weeks ago.  Here's my trend, which I think will calm your mind a bit:

Non - IS

  • July 2011 (3 months): 1.5%
  • Oct 2011 (6 months): 0.16%
  • Jan 2012 (9 months): 0.02%
  • April 2012 (12 months): PCR-u

IS

  • July 2012 (15 months): 0.043%
  • Sept 2012 (~ 18 months): 0.124%
  • Nov 2012 (~ 19 months): 0.125%

So at ~ 19 months into Gleevec 400mg, I went CMR (on I think a less sensitive test), grew a bit, then flattened right at the edge of MMR.  No spikes.  Great = no.  Good enough = yes.  Why? = I have no idea.  FISH was negative, so I'm CCyR and get to live for now.  Doc has zero concern, says I'm doing great, stay the course on 400mg, and next PCR in April 2013.

So, I'm drinking a glass of wine this evening because I get to live for now ... why not?  And I started some serious ankle PT with an athletic trainer today, and I got to run for a mile on a weight-controlled treatmill - at 7 minutes a mile - I haven't done that for many months - Woo Hoo!! (although only at 55% of my body weight, LOL).  So I'm hopeful that I'll get back to my 44 minute 10Ks and continue to smoke people in races who aren't living with chronic cancers in their bodies.  And for the record, I'm completely healthy (aside from some understandable anxiety), rarely get sick, very athletic (once my ankle is strong again), own a small business and travel, raising three kids with my wife and life is great.  I am counting my blessings that I've at least leveled off and get to continue living a healthy life.  I am going to celebrate it, because I can't control the results any further (I take my daily dose as prescribed).  Maybe 8g of Circumin daily .... eventually, but I'm not ready to try it out yet.

I'm still going to post and ask what other folks would do in my situation, but does this settle you at all?  I hope so -- I'm enamored with the details like you, and I wasn't sleeping for a few days, etc. - but I am quickly convincing myself that "good enough" is what counts.

Keep it up Pin, you're doing a great job and you'll either level off (probably lower than me), or trend back down and go undetectable.  Either way, you're going to be fine.


Dan - Atlanta, GA

CML CP Diagnosed March 2011

Gleevec 400mg


#10 Trey

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Posted 15 November 2012 - 08:26 PM

Pin,

Now for my next trick, I will predict what your next PCRs will look like:

SO FAR:

EXTRAPOLATION BASED ON TREY'S PROPRIETARY PCR PREDICTOR ALGORITHM:



#11 Pin

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Posted 15 November 2012 - 10:01 PM

Dan! Good to hear from you again - and you got your results back. Wow - this just keeps adding pieces to this never ending puzzle doesn't it? I am glad you are stable at least, that gives you plenty of time to make a decision. I'll answer your other post too. Glad you are getting back into the running - man would I be pleased with myself if I could run 10k in 44mins!! I know you will get back there. Anyway, I can't write ok much as I am in the car (not driving!) on the way to a wedding at the beach. Trying to enjoy myself for now and to see things as you are, we are doing everything we can aren't we - and that's all we can do :) Pin.


Diagnosed 9 June 2011, Glivec 400mg June 2011-July 2017, Tasigna 600mg July 2017-present (switched due to intolerable side effects, and desire for future cessation attempt).

Commenced monthly testing when MR4.0 lost during 2012.

 

2017: <0.01, <0.01, 0.005 (200mg Glivec, Adelaide) <0.01, 0.001 (new test sensitivity)

2016: <0.01, <0.01, PCRU, 0.002 (Adelaide)

2015: <0.01, <0.01, <0.01, 0.013

2014: PCRU, <0.01, <0.01, <0.01, <0.01

2013: 0.01, 0.014, 0.016, 0.026, 0.041, <0.01, <0.01 

2012: <0.01, <0.01, 0.013, 0.032, 0.021

2011: 38.00, 12.00, 0.14


#12 Pin

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Posted 15 November 2012 - 10:08 PM

Haha - me being me, I am desperately trying to read into what this might mean (Big Dipper - my PCRs will dip and then go up? 'Pin'wheel for Pin? Is this prophetic? My results will go up and then join back up like a saucepan to where they were? You think I look like a bear?). But then I realised you were just poking fun! I'm sure I'm not the only one that thinks you have some kind of 'future reading ability' though! Thanks for making me laugh :)


Diagnosed 9 June 2011, Glivec 400mg June 2011-July 2017, Tasigna 600mg July 2017-present (switched due to intolerable side effects, and desire for future cessation attempt).

Commenced monthly testing when MR4.0 lost during 2012.

 

2017: <0.01, <0.01, 0.005 (200mg Glivec, Adelaide) <0.01, 0.001 (new test sensitivity)

2016: <0.01, <0.01, PCRU, 0.002 (Adelaide)

2015: <0.01, <0.01, <0.01, 0.013

2014: PCRU, <0.01, <0.01, <0.01, <0.01

2013: 0.01, 0.014, 0.016, 0.026, 0.041, <0.01, <0.01 

2012: <0.01, <0.01, 0.013, 0.032, 0.021

2011: 38.00, 12.00, 0.14


#13 Guest_billronm_*

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Posted 15 November 2012 - 11:28 PM

HUH?



#14 Pin

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Posted 11 December 2012 - 08:09 PM

Hi everyone, I got my latest (17 month) pcr test back and it came in at 0.02%. I'm relieved, flat is good (down is better!) but flat is good - and good is good enough

Just starting to wonder now if perhaps the initial increase had something to do with changing to night dosing (could be a coincidence, but I switched to night right after my 12 month appointment) - everyone says no, but I do wonder about the subtle differences in drug absorption on occasion...Anyway, when I spoke to the registrar who gave me my results she asked if I had been sick with "gastro" over the past few months (i.e., vomiting and diarrhoea) as maybe that could be a reason. I said, not really, but in general I experience the big D frequently (as do we all!) but even more so with the night time dosing than I did with the morning (not sure why, could have been a coincidence with when I switched). I probably get it about 3-4 times per week  within 1/2 an hour to an hour after taking my pill in addition to other extremely convenient times of day.

Anyway, it may be nothing to do with this and maybe it is not important and ew - gross, but does anyone have an opinion on this or any experience to add?


Diagnosed 9 June 2011, Glivec 400mg June 2011-July 2017, Tasigna 600mg July 2017-present (switched due to intolerable side effects, and desire for future cessation attempt).

Commenced monthly testing when MR4.0 lost during 2012.

 

2017: <0.01, <0.01, 0.005 (200mg Glivec, Adelaide) <0.01, 0.001 (new test sensitivity)

2016: <0.01, <0.01, PCRU, 0.002 (Adelaide)

2015: <0.01, <0.01, <0.01, 0.013

2014: PCRU, <0.01, <0.01, <0.01, <0.01

2013: 0.01, 0.014, 0.016, 0.026, 0.041, <0.01, <0.01 

2012: <0.01, <0.01, 0.013, 0.032, 0.021

2011: 38.00, 12.00, 0.14


#15 GerryL

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Posted 11 December 2012 - 11:55 PM

Hi Pin,

I still suspect your herbs. Good news though now that it has dropped again, even if it is only slightly. I have similar issues to you on occasion, but in the morning when I take the Gleevec.

I sit at my desk this afternoon with puffy ankles from the heat of the day and the glass of wine I had with lunch, starting to look like a switch to Tasigna may not be that bad after all. LOL.

Dr. Michael Mauro talked a little about the toxicity of the TKI for patients, which is what if feels like is happening with me. http://www.patientpo...nt-and-research



#16 jjg

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Posted 12 December 2012 - 06:28 AM

Hey pin, it's a pretty good result and flat is very good considering one of the alternatives. I hope you are more settled.


Dx Dec 2010 @37

2x IVF egg collection

Glivec 600 & 800mg

PCRU March 2012

Unsuccessful pregnancy attempt - relapsed, 3 months interferon (intron A), bad side effects from interferon

Nilotinib 600mg Oct 2012

PCRU April 2013, 2 years MR4.5 mostly PCRU with a few blips

April 2015 stopped again for pregnancy attempt (donor egg), pregnant first transfer, 0.110 at 10wks, 2.1 at 14wks, 4.2 at 16wks, started interferon, slow dose increase to 25MIU per wk, at full dose PCR< 1 for remainder of pregnancy

Healthy baby girl Jan 2016, breastfed one month

Nilotinib 600mg Feb 2016

MMR May 2016

PCRU Feb 2017


#17 Pin

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Posted 13 December 2012 - 08:26 PM

Yeah - it's definitely still a possibility, hopefully time will tell... I know what you mean, I'm all puffed up at the moment and the dreaded fatigue (which seemed to be on holidays) has returned again in full force. Ah well, maybe it is just that time of year again, hot, puffy and sleepy!


Diagnosed 9 June 2011, Glivec 400mg June 2011-July 2017, Tasigna 600mg July 2017-present (switched due to intolerable side effects, and desire for future cessation attempt).

Commenced monthly testing when MR4.0 lost during 2012.

 

2017: <0.01, <0.01, 0.005 (200mg Glivec, Adelaide) <0.01, 0.001 (new test sensitivity)

2016: <0.01, <0.01, PCRU, 0.002 (Adelaide)

2015: <0.01, <0.01, <0.01, 0.013

2014: PCRU, <0.01, <0.01, <0.01, <0.01

2013: 0.01, 0.014, 0.016, 0.026, 0.041, <0.01, <0.01 

2012: <0.01, <0.01, 0.013, 0.032, 0.021

2011: 38.00, 12.00, 0.14


#18 Pin

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Posted 13 December 2012 - 08:32 PM

Thanks, I am feeling better about this one than the last that's for sure


Diagnosed 9 June 2011, Glivec 400mg June 2011-July 2017, Tasigna 600mg July 2017-present (switched due to intolerable side effects, and desire for future cessation attempt).

Commenced monthly testing when MR4.0 lost during 2012.

 

2017: <0.01, <0.01, 0.005 (200mg Glivec, Adelaide) <0.01, 0.001 (new test sensitivity)

2016: <0.01, <0.01, PCRU, 0.002 (Adelaide)

2015: <0.01, <0.01, <0.01, 0.013

2014: PCRU, <0.01, <0.01, <0.01, <0.01

2013: 0.01, 0.014, 0.016, 0.026, 0.041, <0.01, <0.01 

2012: <0.01, <0.01, 0.013, 0.032, 0.021

2011: 38.00, 12.00, 0.14


#19 Pin

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Posted 28 January 2013 - 11:43 PM

Hey everyone, I have yet another piece to add to my own personal puzzle.

My latest test came back at .01%, which is good - stable is stable, and stable is good enough.

But here's the interesting part - my imatinib trough level test came in at around 300-400ng/mL (the plasma one was 300 and something, and the other one, which I only briefly glanced at on the screen was 400 and something). They're meant to be at 1000 ng/mL. Interesting. Well for me anyway. Kind of irritating that at regular dose I am less than half of what I'm meant to be right now.

So clearly something (read: herbal or otherwise) has had an impact on my systems drug-clearance ability and I'm just "maintaining" response for now at a pretty low level of drug at trough. What remains to be seen is, will I somehow get my trough concentration levels back up to 1000 or more? Or do I even need this? Surely they had to have been there at some point in order to get to where I am now? And where I have been.

Trey - I know this blood levels stuff is all very unfashionable now, but do you have an opinion on this?


Diagnosed 9 June 2011, Glivec 400mg June 2011-July 2017, Tasigna 600mg July 2017-present (switched due to intolerable side effects, and desire for future cessation attempt).

Commenced monthly testing when MR4.0 lost during 2012.

 

2017: <0.01, <0.01, 0.005 (200mg Glivec, Adelaide) <0.01, 0.001 (new test sensitivity)

2016: <0.01, <0.01, PCRU, 0.002 (Adelaide)

2015: <0.01, <0.01, <0.01, 0.013

2014: PCRU, <0.01, <0.01, <0.01, <0.01

2013: 0.01, 0.014, 0.016, 0.026, 0.041, <0.01, <0.01 

2012: <0.01, <0.01, 0.013, 0.032, 0.021

2011: 38.00, 12.00, 0.14


#20 GerryL

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Posted 29 January 2013 - 12:43 AM

Perhaps your liver is working really well now Pin and flushing out the Gleevec quickly. How are the side effects going?






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