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BCR-ABL1

I'm Ray from USA, age 70, CML 27 months now . I'm veteran and use the Veterans Hospital

My last test: Sept 2018:  b2a2  .0032%, b3a2 .1123%, ela2 .0032%.    .0032 is lowest detectable number from lab. 

I've been on Imatinub 600 mg since day one.  I asked for reduction to 400 mg and was told no without explanation. Can anyone help with this question?

When told I had cancer I was scared. Did what I was told and never offered any other alternatives.  (a good soldier) Finally after the two years (out of denial and scared) I'm asking questions.  Love this site!!!

Update 12/16/2018:  Test  results 08/31/2016:  b2a2,  72.866%  b3a2.  48.651%  ela2, 0.093%  These are my starting numbers, when I was diagnosed.

 

Hi Ray and welcome,

I can see no good reason why your clinician has refused a dose reduction. The standard dose for imatinib is 400mg, and your response has obviously been optimal. 

Continue to ask questions... especially of your doctor, but also of us on this site. We are all CML patients, so are more likely to know how you're feeling. 

Sandy

Hi Ray, welcome.

It is unusual for anyone to start on 600mg imatinib daily; 400mg has been the conventional starting dose for a long time. Was there something unusual about your case at diagnosis?If your doctor at the Veteran's facility does not see many patients with CML you may need to help him keep up to date on current thinking on dose reduction.

In my case after over 10 years on imatinib I reduced from 400mg to 200mg per day, and maintained MMR. I have now stopped taking the pills and the Destiny trial results indicate that someone with my results has a chance of up to 70% of staying in MMR. Prof Clarke's talk at the recent conference (link on the homepage) has a lot of information on dose reduction protocols.

I hope this helps.

Alastair

Sandy and AlastairC

Thank you both for your responses, and great input.  I wasn't made aware of any crisis at the beginning.  Starting numbers were, b2a2: 72.866%, b3a2:48.651%, ela2: .093%    Thanks to this forum, the videos here, also the questions to ask section I'm much more informed.  I've also been to private wellness Dr to help me get my body defiencies back on track.  I asked VA for blood work last Friday and they seemed really upset I've went outside the system. Dr I went to is 40 yrs medical Dr, holds 4 board certifications (25 yrs ER Dr)  He now uses both modern medicine techniques and natural techniques for body healing.  Was recommended by my Son and has great reviews.  The Imatinib, creates much joint pain, diarrhea and energy loss.  I will read about the DESTINY study.  I think the VA is so overwhelmed, the level of personal care is suffering.  It's my humble opinion that when we get to a certain age we are put off.  I've been told numerous times how well I'm doing compared to other vets.  However, I'm a lifelong non smoker, have controlled the alcohol consumption and spent much time in the gym.  

AlastairC

I did read about your journey of meds reduction in another post.  Very inspiring!!! One of the main reasons why I joined this site.  Right now I have 17 questions for my oncologist.  I've signed up for a program where I can do this from my computer at home, directly to him.  I've also been checking on the internet for a private sector oncologist.  I have all blood tests for the last 27 months. It's empowering to learn about the cancer and be able to ask questions.

Thank you

Ray

Hi Ray

I'm delighted that some of my posts have been useful to you.

In terms of identifying another oncologist I can't help from UK, but there are some US folks on this site who know where the expertise is. If you can let us know where you are located one of them may be able to suggest someone reasonably close. Your VA doctor sounds very experienced, but those ER years say to me that they may not be a CML specialist. TKIs have been developed since he or she qualified. Their use is developing fast - 11 years ago when I was diagnosed there was no talk of dose reduction - so someone who is able to stay up with current developments may be of use to you.

Let us know how you get on with the 17 questions, and use your military training to make sure you get the answers you need.

Alastair

Hey Alistair

The city closest to me is Boise, in the state of Idaho.  It would be great to have a good recommendation of a Dr in my area.  Thank you again

Ray

Sir your response is much better than my mother's and she is on 200 mg since beginning of these year, also except first month she has been on 300 mg. 

But not sure about what does your test results mean ! like b3a2 etc . her values are for BCR-ABL ( IS )

my mother's results and dosage from the start of treatment.  

BCR-ABL (IS)

54.61  Oct 2015  DX

1.088  July 2016 ( 9 th month )

0.116  Oct 2016

0.030  Jan 2017 

0.152  April 2017   ! Lost MMR !

0.065  May 2017

0.085  Sept 2017

0.046  Dec 2017

0.041 April 2018  @200 mg

0.018 August 2018 @200 mg

Gleevec

400 mg 28 October 2015  - 26 November 2015

300 mg 26 November 2015 - 23 January 2018

200 mg 23 January 2018 to present

+

* 16-24 March 2016 stopped due to neutropenia

* 200 mg 24 March 2016- 07 April 2016

* 300 mg 07 April 2016-28 April 2016

* 200 mg 28 April 2016 - 23 May 2016 200 mg

Alliswell

Thank you for your response.  I have according to lab results BCR ABL1.  I'm not exactly sure what b2a2, b3a2  and  e1a2 really mean and that is on my list for the oncologist at out next meeting. The oncologist called them markers.  I've had severe joint pain, muscle cramps in back of legs, tennis elbow and forearm pain.  Got really hard to turn a door knob.  And the diarrhea was horrible.  I've reduced on my own, from 600 mg now at 400 mg of Imatinib.  The symptoms are soo much better.  I was early stage, no blasts. They did tell me I would be on meds rest of my life.  Not sure how that was determined.  That is another question I have for him.  Depending on the answers I get at next visit, especially in regards to future plans and meds reductions, will determine if I go for another Doctors 2nd opinion.  This site and the people here are wonderful and have helped so much.  Thank you for your reply and input.  Greatly appreciated

Ray

Hi Ray, I was diagnosed in April 2017 and am also on imatinib ever since, 400 mg daily. My oncology care here in Western Montana is very good but I went to Dr. Druker in Portland OR last month for a second opinion. It was a wonderful, comprehensive medical appointment. His knowledge is very deep since he only sees CML patients, as I understand it, and he is very good at explaining the disease. Good luck to you!

Hi Ray from USA ...

It's good you are asking questions and feel more confident in learning more and deciding your own course of action.

Your doctors are correct, you are doing very well - but you can do better ... in terms of how you feel. It's fair to thank the "system" for identifying your CML and getting you on treatment which led you to success. As I tell many others - you will not die from CML. That's done - simply because it's been caught early. And treatment is very successful.

It's the side effects and quality of life you want to tackle next.

First - you can lower your dose to lower side effects. No need taking 600 mg Imatinib when 400 is the standard and will likely continue working for you. Why you were started at 600 mg should be explained (any blast cells observed during diagnosis for example and how many). You can also switch drugs (to dasatinib, for example) to eliminate gleevec side effects (but add dasatinib side effects which may bother you less).

Second - You should consider taking 400-500 mg per day magnesium citrate or magnesium taurate (I take taurate). Imatinib (Gleevec) causes magnesium depletion in the body leading to muscle and join ache for many. Taking additional magnesium (which even non-cml people should be doing) will help normalize your magnesium and decrease muscle and joint aches - you'll sleep better too. Magnesium is vital for heart health. There are other supplements for which food does not supply like it did 100 years ago you should also consider (vitamin D, K2).

Third - ask your 17 questions here. Take the answers with you and compare to what your doctor tells you.

b3a2, ela2, etc. are various breakpoints in human DNA strands leading to the bcr-abl fusion gene which can cause CML disease. (https://www.ncbi.nlm.nih.gov/pubmed/9376660). When the number 9 and number 22 chromosome unravel in the nucleus (during mitosis), bits of nine and 22 can translocate creating a new number 9 and new number 22 chromosome. This leads to a new gene which is called the bcr-abl gene (because the abl gene on chromosome 9 and the bcr gene on chrmosome 22 get mixed up). This new gene, it turns out, transcribes a protein which signals white blood cells to keep dividing and ignore shut down signals. This is why bcr-abl is an "oncogene" (cancer causing).

It's nasty.

Bcr-abl pumps out tyrosine kinase in the bucketful creating CML. Gleevec works in that it is similar in shape to an ATP molecule (energy source) and specifically binds to the ATP site on the transcribing gene (but not in normal cells). It stops the oncogene and cell function and leads to the CML cells dying. But in order to work, the shape of the bcr-abl gene site has to match the gleevec molecule. This is the brilliance of the discovery.

Typical in nature, not everything is identical - but close. The creation of the bcr-abl oncogene is not precise and gleevec is precise. Some of the translocations occur a bit above and a bit below the breakpoints and can even involve other chromosomes besides nine and twenty-two. It's still bcr-abl in that it works the same, but the shape of proteins created are slightly different leading to the gleevec "key" not quite fitting the bcr-abl "lock". It still can work, just not as well.

b3a2 is the most common of the breakpoints (and there are dozens of them) creating the bcr-abl oncogene for which Gleevec is designed (over 90%). Most CML patients by far have this breakpoint and Gleevec works very well for them. But other patients can have other breakpoints for which other drugs are necessary. The good news is that b3a2 seems to have the biggest impact causing disease where the other breakpoints are not as disease causing - they tend to die away (expect for one nasty one - t315i mutation). However, for some patients, b3a2 gets whacked and the other breakpoints grow necessitating a new drug (which happened to me).

In your post above, your dominant b3a2 mutation is at 0.1123%. That is your CML percentage for all practical purposes as measured by PCR. The other variants are not significant and don't matter in this case. It is b3a2 you will be monitoring. You are very close to MMR (major molecular remission). Your goal is for your PCR level (b3as) to drop below 0.1% and then drop below 0.01%. Once that happens you begin a new episode in tracking.

Returning to why you were prescribed 600 mg Imatinib. It's possible you had a lot of blast cells at diagnosis present. This is why your blood count report is important detailing the number, percentage and kinds of blood cells present. At diagnosis you had an overwhelming amount of white blood cells - most of them CML (cancer). Depending on what types of cells were present (i.e. blast cells, neutrophils, basophils, esinophils and on and on ...) determine what stage of disease you started at. I suspect this is why you were started on a higher dose of 600 mg than standard - but without seeing the data, I am just guessing.

I hope this is useful to you. This forum is an excellent resource as you continue your journey. You will end up knowing more about this disease than your doctor. For you - it's your life. For him - it's just a job.

Sorry about my first post , i misinterpretted your PCR results. 

According to scuba ,

In your post above, your dominant b3a2 mutation is at 0.1123%. That is your CML percentage for all practical purposes as measured by PCR. The other variants are not significant and don't matter in this case. It is b3a2 you will be monitoring. You are very close to MMR (major molecular remission). Your goal is for your PCR level (b3as) to drop below 0.1% and then drop below 0.01%. Once that happens you begin a new episode in tracking.

Sorry again for misguidance.

Also Scuba you are a perfect detail in this forum. thanks for all your information that you have given..

the last one .

İ think this forum was US based. you should take a look. 

http://cmlc.ml/     or 

http://cmlc.ml/community.lls.org/forum/27-chronic-myeloid-leukemia/index...

 

and they moved to here i guess. i wasn't aware 

https://communityview.lls.org/groups/chronic-myeloid-leukemia

 

Hi Justine

Thank you.  I'll enter the Dr in my notes. I have blood work in January and Dr appointment.  The best of luck to you

Scuba,  great to meet you and thank you. 

When diagnosed it was a yearly exam and my white blood count was 147000. Was told I had AML.  This was Friday and a long few days before meeting PA (Physicans attendant) in the oncology clinic.  Was told that next Tuesday I didn't have AML, but CML. Quite a relief for me.   Was put on meds to kill off white blood cells.  Went to the 6k mark immediately, then on Gleevic 600mg later changed to Imatinib 600mg.  I had no blasts.  I'm a blessed man

Your comprehensive explanation is what I've been looking for.  I can't thank you enough

The VA Oncology clinic consists of 1 Nurse, several PA's, (1 permanent) and one Dr of Oncology.  I've seen the Dr one time in 28 months.  I understand why and have no ill feelings.  They are so busy with much more ill patients.  When I go there and look around I realize how truly blessed I am.  Yes my detection and modern medicine has and is doing wonders.  

Thank you again for taking the time and explaining CML in such detail

Ray

I

 

Ray - The fact you had no blasts is excellent. It means you were diagnosed in "chronic" phase which is much easier to treat.

I'm surprised they started you on 600 mg Gleevec. Normal starting dose is 400 mg. However, Gleevec is somewhat dose dependent - so if you tolerated the "extra" they gave you, you likely hit CML harder. Given your current status - and no blasts, there is no need for you to tolerate the added side effects. You should consider lowering your dose - at least to 400 perhaps lower.

Let your doctor know you are becoming very well educated on CML, the disease and treatment. An educated patient is in the doctor's (and patients) best interest.

As you track your CML (via PCR testing), also keep in mind your overall health as indicated by typical blood tests such as CBC (complete blood count) and metabolic panel (your liver, fat levels, sugar). Gleevec and other TKI's can impact these markers - liver enzymes especially. This is why good nutritional support will help the TKI do its job.

Given no blasts and where you are - CML is not going to kill you. Something else will - so focus on that. Stay healthy.

Here's a list of my questions.  After much study of my PCR results,,  some of my questions have been answered.'

These are my Oncologist ,  Dr Montgomery's answers today 01/17 

Jan 17, 2019 Blood work and question answers. Jan 2019 B2A2 0.1694  B3A2 0.1482  Vitamin D 16.4 (Sept 2018  B2A2 .0032   B3A2 0.1123)

1.  Have I been Imatinib drug level tested?         01/17  Answer no

2.  Can to much Imatinib be toxic?  01/17 Never asked this question

3.% if people who become Imatinib resistant? 01/17 Never asked this question

4, What % am I in for heart risks, in taking 600 mg Imatinib  for 29 months?     Answer     01/17 Imatinib is easiest on heart

5,  Possible change in meds, lower dosage or different Imatinib?       Answer  01/17 No wait another 6 months

6.% error in testing results? Mine are not consistent?         Answer  01/17 up to 30% error

7.  What level mmr am I? 01/17  Anything under 3.0 is considered MMR

8.  What was beginning white blood cell count? and what kind? % blasts?        Answer   01/17 147K and Neutrophillis and 1% blasts

9. What is my goal, and time frame?            Answer  01/17 Have to wait 6 months

10. Hepatitis B tested? Never asked this question

11,  What is most accurate CML test?  Have I ever received FISH test?        Answer     01/17 QPCR and Never received FISH test

12. Is cutting Imatinib in half advisable? Never asked this question

13.  Has my spleen been tested for enlargement? Never asked this question

14.  Does Imatinib effect vitamin D?          Answer    01/17  Yours was probably low to start

Any suggestions of questions to ask is appreciated.  Jan 3, 2019 I had my 3 month PCR test.  Jan 17, 2019 I meet with Oncologist or PA.    Thank all of you  Ray

 

Sorry, clarification question 12.  Physically cutting a 400 mg in half to complete the dosage of 600 mg.

Others on this forum may add to the answers and offer other questions as well:

Here's a list of my questions.  After much study of my PCR results,,  some of my questions have been answered.

1.  Have I been Imatinib drug level tested?

I suspect not. It usually is not done unless there is an issue. And you are responding.

2.  Can to much Imatinib be toxic?

Yes. All TKI's are toxic. Toxicity increases with dose. So a trade-off between treatment and toxicity.

3.% if people who become Imatinib resistant?

Usually within the first year although can happen later. upwards of 35%. Will be interesting to see how your doctor answers.

4, What % am I in for heart risks, in taking 600 mg Imatinib  for 29 months?

This is an interesting area of study. All TKI's have heart risks - but is easily masked by diet/exercise which exposes you to TKI risk. In other words, eating well will minimize your heart risk due to your lifestyle. Impact of TKI will be in the "noise". It is the main reason I switched to a keto based diet and no longer eat any sugar or processed carbs. I don't eat many carbs at all anymore. Except on special occasions!

In my case, having been diagnosed with CML was a life saver (can't believe I am admitting this ...). It led to my first, in a long time, full physical and blood chemistry tests which exposed all kinds of issues to do lifestyle/diet. I completely reversed these (pre-diabetes - gone, high blood pressure - gone, metabolic syndrome - gone, high bad cholesterol - dropping. Good cholesterol - increasing, etc.  etc.). If I had not developed CML, I likely would have been a heart attack patient or dead. My father had a quadruple bypass and died six years later of a stroke. CML woke me up.

So you should ask your doctor what you can do to improve your overall health so that taking a TKI does not add an issue. Also - take a stress test to reveal any Qt elongation which may be caused by TKI's (especially Nilotinib). As long as subtle heart issues do not show up in stress tests, you are in a good spot regarding TKI heart risk.

5,  Possible change in meds, lower dosage or different Imatinib?

If you find you are stuck around 0.1% PCR changing drugs could be considered. Personally, low dose Dasatinib worked for me (20 mg).

6.% error in testing results? Mine are not consistent?

Can be as high as one log (factor of 10) - So PCR levels beyond the second decimal place are pretty meaningless. And changes to PCR of around 1/2 log is in the noise of the test. However, trends of increasing or decreasing are noteworthy. And there is the psychology - no one likes seeing numbers going up even if it is in the noise of the test. Big jumps should require a re-test to confirm.

7.  What level mmr am I?

You are barely MMR. 0.1% is the threshold. Your doctor should confirm.

8.  What was beginning white blood cell count? and what kind?

Good question to ask. Ask for your CBC test results each time blood is taken. Pay attention to the "absolute" numbers. You may find you have a "new normal" for you which is due to the drug "suppressing" your normal system. This is a side effect and for many not an issue. My red blood is slightly anemic - always has been once I started a TKI. So I won't be running marathons - but feel fine otherwise.

9. What is my goal, and time frame?

at 12 months - great to be MMR. Slow responders are also doing well at 18 - even 24 months. Plateaus are normal too .... you can stay level for months and months and then suddenly start dropping further. Over time, there is evidence CML can burn itself out - but takes years and years.

A good goal is to achieve PCR < 0.01% and stay there or below for two years - ideally 5 years (recent research, Dr. Cortes) before stopping drug treatment and test for treatment free remission.

10. Hepatitis B tested?

Why? Have you been exposed?

11,  What is most accurate CML test?  Have I ever received FISH test?

DNA PCR is the most accurate CML test, but I suspect that is not your question. Your PCR's are at a level where FISH testing is probably not necessary. You absolutely should have had a FISH test at diagnosis and for the first year while your CML was improving. FISH is taken (or should be taken) as long as it is positive (i.e. > zero) and PCR is above 1.0% Once FISH falls to zero, it is no longer relevant. PCR takes over as the canary in the mine shaft. If you haven't had a FISH test, then you probably don't need one now, but I would ask for one just to have the data confirm that FISH = zero.

12. Is cutting Imatinib in half advisable?

No.

13.  Has my spleen been tested for enlargement?

He would feel your abdomen and check for size and tenderness. At your CML level, your spleen is likely fine. It becomes normal very quickly following successful TKI treatment - long before FISH or PCR drops in fact. Mine was normal even at diagnosis (to the touch that is). Chances are he was groping your abdomen when you were first diagnosed.

No need to cut, just break it at the score line in the middle.  I've been doing it for years, not a problem.

Scuba thank you.  FYI, I'm taking magnesium, k and d as you suggested.  I'm sleeping much better.  The VA system is broken.  I've went outside the system to another Dr.  He asked for blood work, I asked VA for blood  work, and they would only do part of it, said it wasn't necessary. I have Dr appointment with VA, 27 Jan and they did blood work for my annual appointment.   I went to private lab and had blood work done VA wouldn't do.  My meeting with ether oncologist or PA is 17 Jan. I'm meeting with private Dr 16 Jan.  Private Dr is 70 yrs old (6 days younger than me) Holds 4 board certifications and practicing 40  plus years.  Preventive medicine and repair is his practice now.  His help is through DIET (much like yours) and exercise.  Extensive blood work to actually see how my body is working.  He is highly recommended through my Son and several people at his work place. I will post results of both appointments.  I think your spot on with your approach.  Good nutrition as you've said will help the TKI's we have to take work, and improve our health.  I'm re thinking things.  I would rather have a good quality of life for a few years, than many years of no quality of life.  This year I celebrated turning 70 on the Mountain Top hunting elk.  I logged 5.7 miles that day in rough and steep terrain.  I'll do better this year. Your and inspiration!!! Thank you Ray

Good to hear of someone cutting/breaking these in half that's been doing it for years.   I've read both ways on internet.  

Thank you for your reply  Ray

I have been cutting a 400mg at the score line for a year now because I’m on 600mg. I contacted my pharmacy to get their take on it. I have read about the contents coming into contact with the mouth, throat, etc. but it’s ok to dissolve in apple juice and drink? Obviously there’s money in it.