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long term TKI use


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#1 SusanL

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Posted 13 July 2016 - 02:54 PM

Can long term TKI use cause bone marrow suppression? or secondary bone marrow cancer?



#2 thatguy

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Posted 13 July 2016 - 11:09 PM

Why are you asking, Susan?
3/25/2015- Dx'ed by FISH : 85% of cells dual-fusion signals, 7% with tri-fusion signals, WBC 212,000. Started Gleevec 400mg.... Calculated .93 SOKAL

08/17/2015- 14.793 % I.S P210 (quest)
10/15/2015- 3.313 % I.S (quest)
12/23/2015- 1.891 % I.S (quest)
1/07/2016- Tasigna 300mg 2x daily
1/14/2016- 4.414 % I.S P210- City Of Hope lab, mutation negative.
1/26/2016- 1.589 % I.S (quest)
2/22/2016- 1.719 % I.S (quest)
2/29/2016- 1.133 % I.S (quest)
3/03/2016- Tasigna 400mg 2x daily.
3/29/2016- 0.663 % I.S (quest)
4/27/2016- 0.781 % I.S (quest)
5/04/2016- 0.652 % I.S.(quest)
5/24/2016- 0.501 % I.S (quest)
6/28/2016-0.534 % I.S (quest)
7/15/2016-0.881 % I.S (quest)
7/22/2016- Bosulif 500mg
7/28/2016- t315i test- Negative
8/22/2016-0.432 % I.S (quest )
11/15/2016-0.325 % I.S (quest)
2/1/2017- .0445% i.s (genoptix)
5/6/2017- .0968% i.s (genoptix)
5/12/2017- .12 % i.s (quest).
6/4/2017- .083% i.s (quest)
6/11/2017- .0295% i.s (genoptix)
8/5/2017- .0501% i.s (genoptix)
11/6/2017- .0270% i.s (genoptix)

#3 SusanL

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Posted 14 July 2016 - 12:24 AM

Been on TKI's for 10.5 yrs.   Blood test past 6 mo have shown iron levels getting lower and lower, hemoglobin lower also but not as much, platelets dropped too.   Onc  emailed me about last weeks results tests and said.  "I have used up all my iron reserves" and we will talk about the whys at appointment next  week.  Of course I had to do my own research and it led me to bone marrow suppression.  I know  there are  lesser reasons for low iron, like internal bleeding, but I just had endoscopy and colonoscopy and was clean.   My experience on this cancer road for the last 13 yrs has made me a little pessimistic and easily gravitate to the worst.



#4 rct

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Posted 14 July 2016 - 07:57 AM

Mrs has been on the just under the line side of every bone marrow measurement since she started Gleevec just over 10 years ago. Her ANC has been non existent at times.

 

Stopping Gleevec causes here marrow measurements to improve, but also shows quick movement of CML.

 

rct



#5 Frogiegirl

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Posted 14 July 2016 - 08:07 AM

rct Just curious has your wife been on gleevec the whole time since diagnosis? also how long had she gone off and the cml showed its ugly face? In other words how quickly did numbers start to rise up? I'm just collecting my own data, been thinking of going off drug for a baby, but unsure if I'd make it through without losing my life.


Diagnosed Oct 2013 Started 600mg of Tasigna  on Nov 4th. Lowered dose a few months later to 300mg due to side affects stayed here declining PCR until March 2015 small jump from 0.0072 to 0.0083 scarred my doc into full dose of Tasigna again 600mg(been miserable since) but reached PCRU 06/15/2015(next test) and have been there ever since. Hoping to have another little one. I have the support of my doc to go off anytime, just scared to jump. might go two years PCRU but he said it wont make much of a difference. I just figured I could possibly go into a trial while preggers if I got the two years behind me.

Nov 8th 2017 went off Tasigna

Dec 1st PCRU off TKI

Jan 5th PCR Detected .0625

Feb 1st PCR Detected .7815

Added 8-6 grams Curcumin daily in Feb

March 3rd PCR Detected 3.2646 YIKES!

 stopped trying for baby after February reading. will start new TKI march 16th 2017 (Sprycel)

FYI I'm not done trying for my last little one.


#6 scuba

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Posted 14 July 2016 - 08:21 AM

rct Just curious has your wife been on gleevec the whole time since diagnosis? also how long had she gone off and the cml showed its ugly face? In other words how quickly did numbers start to rise up? I'm just collecting my own data, been thinking of going off drug for a baby, but unsure if I'd make it through without losing my life.

 

"but unsure if I'd make it through without losing my life."

 

You are NOT going to lose your life to CML. I stopped for nine months before resuming sprycel and my PCR barely rose one log (i.e. from <0.01% to 0.09%) in that time. When I resumed Sprcyel (20mg), my PCR fell back fast to below 0.01% (M.D. Anderson scale). Of course I do take Curcumin and maintain higher than normal vitamin D status. 


Diagnosed 11 May 2011 (100% FiSH, 155% PCR)

with b2a2 BCR-ABL fusion transcript coding for the 210kDa BCR-ABL protein

 

Sprycel: 20 mg per day - taken at lights out with Quercetin and/or Magnesium Taurate

6-8 grams Curcumin C3 complex.

 

2015 PCR: < 0.01% (M.D. Anderson scale)

2016 PCR: < 0.01% (M.D. Anderson scale) 

March        2017 PCR:     0.01% (M.D. Anderson scale)

June          2017 PCR:     "undetected"

September 2017 PCR:     "undetected"


#7 thatguy

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Posted 14 July 2016 - 10:50 AM

Can long term TKI use cause bone marrow suppression? or secondary bone marrow cancer?


I had heard of Marrow suppression being a possible effect of the meds, but never secondary marrow cancer...don't go there Susan! Sounds like my recent self-dianoses!
3/25/2015- Dx'ed by FISH : 85% of cells dual-fusion signals, 7% with tri-fusion signals, WBC 212,000. Started Gleevec 400mg.... Calculated .93 SOKAL

08/17/2015- 14.793 % I.S P210 (quest)
10/15/2015- 3.313 % I.S (quest)
12/23/2015- 1.891 % I.S (quest)
1/07/2016- Tasigna 300mg 2x daily
1/14/2016- 4.414 % I.S P210- City Of Hope lab, mutation negative.
1/26/2016- 1.589 % I.S (quest)
2/22/2016- 1.719 % I.S (quest)
2/29/2016- 1.133 % I.S (quest)
3/03/2016- Tasigna 400mg 2x daily.
3/29/2016- 0.663 % I.S (quest)
4/27/2016- 0.781 % I.S (quest)
5/04/2016- 0.652 % I.S.(quest)
5/24/2016- 0.501 % I.S (quest)
6/28/2016-0.534 % I.S (quest)
7/15/2016-0.881 % I.S (quest)
7/22/2016- Bosulif 500mg
7/28/2016- t315i test- Negative
8/22/2016-0.432 % I.S (quest )
11/15/2016-0.325 % I.S (quest)
2/1/2017- .0445% i.s (genoptix)
5/6/2017- .0968% i.s (genoptix)
5/12/2017- .12 % i.s (quest).
6/4/2017- .083% i.s (quest)
6/11/2017- .0295% i.s (genoptix)
8/5/2017- .0501% i.s (genoptix)
11/6/2017- .0270% i.s (genoptix)

#8 SusanL

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Posted 14 July 2016 - 11:41 AM

that guy

  thanks for the reminder to not  invite trouble in, at least not until it knocks.

 

A few were asking about stopping TKI.  I have done that when on Tasigna and PCR #'s went up quickly within 2 months but upon resuming on new TKI, Bosulif it just as quickly went back down to where it stays.  Undetectable positive where I've been most of the 10 yrs. 



#9 Buzzm1

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Posted 14 July 2016 - 11:56 AM

that guy

  thanks for the reminder to not  invite trouble in, at least not until it knocks.

 

A few were asking about stopping TKI.  I have done that when on Tasigna and PCR #'s went up quickly within 2 months but upon resuming on new TKI, Bosulif it just as quickly went back down to where it stays.  Undetectable positive where I've been most of the 10 yrs. 

SusanL, what is your current Bosulif dosage?? tia...


For the benefit of yourself and others please add your CML history into your Signature

 

02/2010 Gleevec 400mg

2011 Two weakly positives, PCRU, weakly positive

2012 PCRU, PCRU, PCRU, PCRU

2013 PCRU, PCRU, PCRU, weakly positive

2014 PCRU, PCRU, PCRU, PCRU (12/07 began dose reduction w/each continuing PCRU)

2015 300, 250, 200, 150

2016 100, 50/100, 100, 10/17 TFR

2017 01/17 TFR, 04/18 TFR, 07/18 TFR 0.0012, 08/29 TFR 0.001, 10/17 TFR 0.000

2018 01/16 TFR 0.0004 ... next quarterly PCR 04/17

 

At the earliest opportunity, and whenever possible, lower your TKI dosage; TKIs are toxic drugs and the less we take longterm the better off we are going to be ... this is especially true for older adults.  

 

In hindsight I should have started my dosage reduction two years earlier; it might have helped minimize some of the longterm cumulative toxic effects of TKIs that I am beset with.  

 

longterm side-effects Peripheral Artery Disease - legs (it's a bitch); continuing shoulder problems, right elbow inflammation.   GFR and creatinine vastly improved after stopping Gleevec.

 

Cumulative Gleevec dosage estimated at 830 grams

 

Taking Gleevec 400mg an hour after my largest meal of the day helped eliminate the nausea that Gleevec is notorious for.  

 

Trey's CML BlogStopping - The OddsStop Studies - Discussion Forum Cessation Study

Big PhRMA - Medicare Status - Social Security Status - Deficit/Debt


#10 Antilogical

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Posted 14 July 2016 - 01:52 PM

SusanL - I've been on Gleevec for over 4 years, and like you, I've recently had issues with depletion of iron reserves and hemoglobin beyond what has been "normal" for me on Gleevec.  Tests have shown nothing so far, and I've been getting IV iron infusions while the docs (pcp, hem/onc, & gi) try to figure out what's going on.  Next week, I'm to have an endoscopy, during which they'll do biopsies for Celiac Disease.  Anemia is one of many side effect of the disease, and I have other complaints that are making my doctor suspicious of that diagnosis.  My hope is that the test is positive so I can move on with my life.  I'm sooooo tired of tests.  My dance card is full of them.


Dx: Sudden severe anemia detected 07/2011, followed by WBC spike. CML Dx 02/2012.

Rx: 03/2012-Gleevec400.  Reduced 02/2013 to Gleevec300 due to side effects (low blood counts).

Response: PCR-Und within 7 mo. on G400. Maintained MMR4-MMR4.5 on G300. PCR-Und since 02/2016.


#11 Jamie2015

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Posted 14 July 2016 - 04:33 PM

Susan,
I too just went to the doctors for my 6 month check up and was told my hemoglobin and iron are low. I have been on sprycel 100mg. My doctor is lowering my dose from 100 mg to 70 mg daily in hopes of that helping.

If it's not one thing it's another.

#12 SusanL

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Posted 14 July 2016 - 11:31 PM

I started on Bosulif 2 1/2 yrs ago at 500 mg.  1 yr ago the diarrhea became a daily problem, every morning for 3 hrs. Dr. lowered dose to 400 mg and it has been tolerable.  In 10 1/2 yrs, and trying all 4 TKI's, I have never been PCRU, and probably never will be so Dr. is open to lower doses to reduce side effects.  For me, Bosulif has been the TKI with the least side effects



#13 Buzzm1

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Posted 14 July 2016 - 11:46 PM

I started on Bosulif 2 1/2 yrs ago at 500 mg.  1 yr ago the diarrhea became a daily problem, every morning for 3 hrs. Dr. lowered dose to 400 mg and it has been tolerable.  In 10 1/2 yrs, and trying all 4 TKI's, I have never been PCRU, and probably never will be so Dr. is open to lower doses to reduce side effects.  For me, Bosulif has been the TKI with the least side effects

SusanL, thanks for that info; a few others here are having great success on Bosulif 300mg, namely chriskuo and mbrown; perhaps Bosulif 300mg might serve to lessen your unwanted side-effects without sacrificing PCR.  Bosulif 500mg seems to be too much to handle; re: chriskuo and Tucker1.  The jury is still out on Bosulif 400mg, especially for those who are on the senior side of life.  You and Tucker1 are the only patients on this forum I know of on that dosage.  No good reason to be on a heavy dosage unless it is absolutely necessary.  Good luck to you.  


For the benefit of yourself and others please add your CML history into your Signature

 

02/2010 Gleevec 400mg

2011 Two weakly positives, PCRU, weakly positive

2012 PCRU, PCRU, PCRU, PCRU

2013 PCRU, PCRU, PCRU, weakly positive

2014 PCRU, PCRU, PCRU, PCRU (12/07 began dose reduction w/each continuing PCRU)

2015 300, 250, 200, 150

2016 100, 50/100, 100, 10/17 TFR

2017 01/17 TFR, 04/18 TFR, 07/18 TFR 0.0012, 08/29 TFR 0.001, 10/17 TFR 0.000

2018 01/16 TFR 0.0004 ... next quarterly PCR 04/17

 

At the earliest opportunity, and whenever possible, lower your TKI dosage; TKIs are toxic drugs and the less we take longterm the better off we are going to be ... this is especially true for older adults.  

 

In hindsight I should have started my dosage reduction two years earlier; it might have helped minimize some of the longterm cumulative toxic effects of TKIs that I am beset with.  

 

longterm side-effects Peripheral Artery Disease - legs (it's a bitch); continuing shoulder problems, right elbow inflammation.   GFR and creatinine vastly improved after stopping Gleevec.

 

Cumulative Gleevec dosage estimated at 830 grams

 

Taking Gleevec 400mg an hour after my largest meal of the day helped eliminate the nausea that Gleevec is notorious for.  

 

Trey's CML BlogStopping - The OddsStop Studies - Discussion Forum Cessation Study

Big PhRMA - Medicare Status - Social Security Status - Deficit/Debt


#14 Melanie

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Posted 15 July 2016 - 12:40 AM

Just thought I'd pipe in to update my dosage of Bosulif. After 3 wonderful months at 300 mg, I've had to go back to 400 mg due to PCR increase. I was only MMR for a short while before reducing dosage to hopefully help with suppressed numbers. Probably just too early. My numbers did improve though...HBG just shy of normal (first time in years) and platelets up to 114, although I take a trial drug for low platelets. Unfortunately, my ANC topped out at 0.9, with only a few test below 0.5. Didn't feel quite as fatigued on 300 and only been back on 400 for a week and can feel another layer of fatigue coming on.
Susan, I'm happy you're finding the Bosulif has less side effects for you. Me too. Marrow suppression ... Maybe a side effect of Long term Bosulif use, since little is known about its long term effects. Similar to PE with Spycel. Please let us know what your dr says about it.
Dx - 05/2011; PCR: 15.04; Fish: 87% Slow responder due to pancytopenia. Current - Bosulif - Nov: 2012, Mar 2016 lowered to 300 mg. 07/16 back to 400 mg. Clinical trial drug, Promacta, Feb 2013, for low Platelets.
CyCR - Aug 2014, Positive for 1 chromosome Sep 2015. PCR: 12.77 in Oct, 2012 to 0.04 (MDA) in Mar, 2016. 4/2016 - 0.126 (Local lab (IS); 05/2016 - 0.195 (local); 6/2016 - 0.07 (MDA); 7/2016 - 0.03 (local) 9/13/2016 - 0.16 (MDA); 9/26/2016 - 0.31 (MDA); 11/2016 - 0.012 (local); 01/2017 - 0.24 (MDA); 04/2017 - 0.09 (MDA); Cytogenetics show der(1:7)(q10;p10)7 chromosome mutation. Repeat of Sep 2015. PCR - 6/2017- 0.035 (local); 10/2017- 0.02 (MDA)

#15 Trey

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Posted 15 July 2016 - 03:26 PM

If the term "marrow suppression" means lower blood counts, then TKI drugs certainly can affect that.  But it is short term TKI use which causes the most impact, rather than long term use.  For most people the body reaches an accommodation over time (for some that is not as good an accommodation as for others) so the longer term impact is often reduced.  For a few that is still not good enough.  But overall the long term impact is often less than the short term impact.  And "suppression" does not mean ineffective.

 

Regarding secondary bone marrow cancers: None are known or suspected. 



#16 rct

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Posted 18 July 2016 - 07:55 AM

rct Just curious has your wife been on gleevec the whole time since diagnosis? also how long had she gone off and the cml showed its ugly face? In other words how quickly did numbers start to rise up? I'm just collecting my own data, been thinking of going off drug for a baby, but unsure if I'd make it through without losing my life.

 

Yes, Gleevec.  A short week of Tasigna, but that didn't work out.  Two PCRs that  month, one PCRu followed by two weeks of no Gleevec in order to start taking Tasigna, then another, 0.0 something, so up to one decimal place away.  Quite a change in only two weeks.

 

She has been off as long as 6 weeks, which provided full recovery of her marrow functions, ANC to White count ratio was perfect, all reds in the right spot, but CML was up in high single digit thousands.

 

What works or doesn't for her may or may not work for you.  Good luck with it.

 

rct



#17 rct

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Posted 18 July 2016 - 07:58 AM

"but unsure if I'd make it through without losing my life."

 

You are NOT going to lose your life to CML. I stopped for nine months before resuming sprycel and my PCR barely rose one log (i.e. from <0.01% to 0.09%) in that time. When I resumed Sprcyel (20mg), my PCR fell back fast to below 0.01% (M.D. Anderson scale). Of course I do take Curcumin and maintain higher than normal vitamin D status. 

 

You are aware that every day people die from CML, right?  You do know there are plenty of blogs and other kinds of pages of people that have had CML go really horribly wrong, right? If you aren't, you should be.  What you do has absolutely nothing to do with what other people do, otherwise there would not have been an 85% or so mortality rate within three years prior to Gleevec.

 

Ticks me off.  New people come here and see this?  And then people get all mad because their doctors tell them not to read the internet.  Here's why they do that, stuff like this right here.

 

Curcumin and  Vitamin D in Elephant sized quantities do nothing for CML, since we're diagnosing and treating here.

 

rct



#18 scuba

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Posted 18 July 2016 - 09:04 AM

You are aware that every day people die from CML, right?  You do know there are plenty of blogs and other kinds of pages of people that have had CML go really horribly wrong, right? If you aren't, you should be.  What you do has absolutely nothing to do with what other people do, otherwise there would not have been an 85% or so mortality rate within three years prior to Gleevec.

 

Ticks me off.  New people come here and see this?  And then people get all mad because their doctors tell them not to read the internet.  Here's why they do that, stuff like this right here.

 

Curcumin and  Vitamin D in Elephant sized quantities do nothing for CML, since we're diagnosing and treating here.

 

rct

 

rct  - sorry you're ticked off, but my comment stands - people who achieve PCRU don't die from CML. What happened prior to Gleevec is irrelevant. It's what is happening now that is important. There has been tremendous progress and we are learning how to manage this disease to the point where once milestones are achieved (CCyR, MMR) those patients will not die from CML. That's my point. What I do is what enabled me to reduce my dose (my opinion) so that side effects are not felt and still maintain near PCRU levels.

 

Survival rates for chronic myeloid leukemia

Highly effective drugs to treat most cases of chronic myeloid leukemia (CML) first became available in 2001. There is no accurate information yet on how long patients treated with these drugs may live. All that is known is that most patients who have been treated with these drugs, starting in 2001 (or even before), are still alive.

One large study of CML patients treated with imatinib (Gleevec®) found that about 90% of them were still alive 5 years after starting treatment. Most of these patients had normal white blood cells and chromosome studies after 5 years on the drug.

Last Medical Review: 02/24/2015
Last Revised: 02/22/2016

from: http://www.cancer.or...-survival-rates


Edited by scuba, 18 July 2016 - 12:12 PM.

Diagnosed 11 May 2011 (100% FiSH, 155% PCR)

with b2a2 BCR-ABL fusion transcript coding for the 210kDa BCR-ABL protein

 

Sprycel: 20 mg per day - taken at lights out with Quercetin and/or Magnesium Taurate

6-8 grams Curcumin C3 complex.

 

2015 PCR: < 0.01% (M.D. Anderson scale)

2016 PCR: < 0.01% (M.D. Anderson scale) 

March        2017 PCR:     0.01% (M.D. Anderson scale)

June          2017 PCR:     "undetected"

September 2017 PCR:     "undetected"


#19 tazdad08

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Posted 19 July 2016 - 08:08 AM

You are aware that every day people die from CML, right?  You do know there are plenty of blogs and other kinds of pages of people that have had CML go really horribly wrong, right? If you aren't, you should be.  What you do has absolutely nothing to do with what other people do, otherwise there would not have been an 85% or so mortality rate within three years prior to Gleevec.

 

Ticks me off.  New people come here and see this?  And then people get all mad because their doctors tell them not to read the internet.  Here's why they do that, stuff like this right here.

 

Curcumin and  Vitamin D in Elephant sized quantities do nothing for CML, since we're diagnosing and treating here.

 

rct

I don't think anyone is diagnosing and treating here. We are sharing our experiences with others in this learning curve. If everyone suffered from the side effects as bad as some of us, then they would also want to know what has and is working for other to help relieve the side effects. Being alive means very little if you can't live. I myself push for a balanced quality of life. If that means experimenting with my dosage, then so be it. I have self medicated for over 4 years and am in better shape than I was then. cml is controlled and I get to experience more of the fun things of my 8 year old son growing up than I did 4 years ago. No, I dont feel great, but I do feel better. A dr "practices medicine". Practice until it is perfected. If it had been perfected, there would be no trials for various cml issues.


Diagnosed in September 2011. Tried one year of Sprycel. Had great response. Became undetectable in a few months. Changed to Tasigna hoping for less side effects. Self medicated myself down to 20% dose and held for 3 years before becoming detectable again. It has been a journey that has helped me realize what life is about! I am all about a balanced life. I firmly agree with my decision to lower my dose. What is life if you aren't living? Mine will never be the way it was, but it is going to be as good as I can make it! Drs PRACTICE medicine, we can guide our dr to help us with a better life! Don't settle until it's acceptable to you!


#20 Frogiegirl

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Posted 19 July 2016 - 11:42 AM

Thanks for the replies sorry for any grief my questions caused. but after all, this is a discussion board to which I lean on heavily. I added my response to my signature line, just to give a better idea of my personal situation. I'm greatful for all info on the subject, after all I am trying to make a somewhat informed decision :D


Diagnosed Oct 2013 Started 600mg of Tasigna  on Nov 4th. Lowered dose a few months later to 300mg due to side affects stayed here declining PCR until March 2015 small jump from 0.0072 to 0.0083 scarred my doc into full dose of Tasigna again 600mg(been miserable since) but reached PCRU 06/15/2015(next test) and have been there ever since. Hoping to have another little one. I have the support of my doc to go off anytime, just scared to jump. might go two years PCRU but he said it wont make much of a difference. I just figured I could possibly go into a trial while preggers if I got the two years behind me.

Nov 8th 2017 went off Tasigna

Dec 1st PCRU off TKI

Jan 5th PCR Detected .0625

Feb 1st PCR Detected .7815

Added 8-6 grams Curcumin daily in Feb

March 3rd PCR Detected 3.2646 YIKES!

 stopped trying for baby after February reading. will start new TKI march 16th 2017 (Sprycel)

FYI I'm not done trying for my last little one.





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