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#1 9miler


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Posted 11 October 2011 - 12:14 PM

My oncologist always did a BMB every 6 mos and then BCR for PCR-ABL test every 6 weeks. No wI switched to a new oncologist and hee sees me just every 3 mos and is doing a FISH test instead., I am not as familiar with this, but from what I know, it is not as accurate. Aan anyone fill me in regarding this test and its accuracy? I am concerned primarily because I never reached the 3.0 level with the PCR test and had those level constantly fluctuate from about 1.0-2.2 and have periodic anemia that always returns. Any advice is welcome.


#2 matt92711


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Posted 12 October 2011 - 04:47 AM

My first time posting here and I am still learning about all this but I think I might be able to explain...

When they do FISH testing the lab will look at a few hundred cells and tell you the percentage of those that are positive for BCR-ABL. This test is good for getting a general idea of the percentage of total cells in the body that show the mix-up. The limitation of this test is that once you go below a minimum percent the test is no longer meaningful. If the lab looks at 200 cells and you have less than 1/200 BCR-ABL it is impossible for this test to give any statistical relevant results. Also I think there are some errors which make very low results meaningless. This point is also called a Complete Cytogenetic Response (CCR or CCyR)

PCR testing, involves them taking a sample of your blood (millions of cells) and putting it in some sort of bio reactor that multiplies (amplifies) the BCR-ABL gene many times. Then they look at a sample of that to see how prevelant the BCR-ABL gene is. There are limitations on how much they can amplify the gene which limits the tests accuracy to somewhere between 1/100,000 to 1/1,000,000. Since this test does not count the blood cells straight out of you to come up with a percent, this test is really telling you about detection levels. At a CMR (complete molecuar response) this test is no longer sensitive enough to detect the BCR-ABL. The log reductions is used as a measurement here since by amplifying the BCR-ABL you are exponentially increasing the gene, so each level of exponential growth you go down is a log reduction (each level is 1/10 of the previous level). They have estimates of what each level corresponds to in the body, but it is not as reliable of a percent as FISH is when applicable. With FISH it is easy to say around 75% to of the cells are BCR-ABL and it is meaningful when next time it is around 50%. On the other hand at very low percentages we can measure reduction better than percent, which is why the results from PCR and FISH are not equivalent.

They should only be doing FISH on you if the levels of BCR-ABL cells are high enough that the percentage in the body can be measured by simple counting of a few hundred cells. If your FISH results are too low to be meaningful then I think they should definitely be doing PCR testing or else it would be impossible to actively monitor the disease. I am not so familiar with which log reduction means what, but I think a Log 2 reduction would make FISH no longer relevant as that should be similar to a CCR, if you are closer to a 1 log reduction then the FISH testing may be relevant and accordingly PCR is probably not needed for trend monitoring. If the percent of your BCR-ABL is identifiable with FISH than subsequent FISH will tell you which way it is headed and you don't need Log reductions to tell you that.

I don't know enough to tell you if the frequency of monitoring is too little given your situation, I also don't know if your results should indicate that you get testing for other mutations. In your profile you mention that you were diag 5 years ago (I was diag 9/27/2011, so I only have 2 weeks of education on this subject). Is your WBC normal (are your WBC counts under 10,000)? Did your Oncologist look to see if you have different forms of the BCR-ABL that may be resistant to Gleevec? There are other drugs out there (I started with Tasigna since my diagnosis and did not start with Gleevec. My Oncologist started me on Tasigna and I also went for a consultation with Dr. Eric Feldman at Cornell-Weill and he agreed that he thinks it is the correct first line approach today). Tasigna and Sprycel are effective against certain variants that Gleevec is not as potent against.

If I had to guess, I would be surprised to find out that you have a mutuation that Gleevec cannot touch since you say your levels are staying within a limited range over several years (if you had a Gleevec untouchable mutuation then it most likely would have increased a lot more). On the other hand it would make sense that you have a form that Gleevec can control but is having trouble. One example of this I heard of is where the BCR-ABL gene gets doubled up, giving an extra place that causes the cell to replicate. There are other variants and channels through which the cells can still multiply despite Gleevec latching onto the BCR-ABL. The 2 choices I am aware of for this is to either increase the dosage of Gleevec or try a different TKI like Tasigna or Sprycel.

I am not giving a diagnosis since I do not know enogh clearly, but I am trying to point out the avenues I would pursue with my doctor.

Best of luck and praying you, me and all the people with cancer get well soon.

#3 9miler


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Posted 12 October 2011 - 07:48 AM

Matt, thank you very much for the informative response. I am amazed at your level of understanding, especially if you have only been dealing with this for a few weeks. I will bring up the question to my oncologist at my next appointment. He is very easy to talk to and I k now he will do his best to explain in detail. My clinic is associated with the MAyo Clinis and the University of Minnesota, so I can opt to go to either of these places at any point if I so choose. I may do that to seek a second opinion. Thank you again and best of wishes to you with your illness.


#4 Trey


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Posted 12 October 2011 - 10:24 AM

FISH is actually a better test until it goes negative (or nearly negative, where it has a 1 - 5% false positive rate) which shows CCyR, then PCR is better after that.  But doing PCRs from the beginning is also a good idea.  BMB is probably the most accurate test except for the statistical sampling issue involved of taking 20 dividing cells at random.

#5 LivingWellWithCML


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Posted 12 October 2011 - 10:32 AM

And some oncs prefer to do FISH/PCR on bone marrow, while others prefer running the tests on peripheral blood exclusively.  There was a study done last year that showed peripheral blood FISH/PCR to line up very well with marrow FISH/CTG/PCR.

My CML specialist does peripheral blood only and isn't planning to do marrow again unless needed. 

Dan - Atlanta, GA

CML CP Diagnosed March 2011

Gleevec 400mg

#6 CallMeLucky


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Posted 12 October 2011 - 12:50 PM

The question for the Oncologist is if/when he plans to do a PCR test.  If the answer is "when the FISH goes negative" then that is somewhat reasonable, although I think most experts would agree that PCR testing should be done all along.  If the answer is "I don't do PCR testing" then that is more concerning.  The follow up question would be "without PCR testing how can you accurately track my treatment and determine if I am achieveing key milestones such as a major molecular reponse, which is determined by a 3 log reduction in a PCR test?".  The only justification for not doing a PCR test after FISH is negative is if your doctor believes a Complete Cytogenetic Response is an acceptable end point for treatment and as long as you are CCyR, then things are fine.  I would be concerned if my doctor felt that way as it would be against the stated guidelines for treating the disease, which clearly call for PCR testing.

So a lot of hypotheticals here.  Chances are the response will be that he will do PCR after FISH goes negaitve.  Not ideal, but not necessarily a reason to switch doctors.  If he is of the opinion that PCR tests are not needed for CML patients on TKI drugs, then you should probably find another doctor.

Date  -  Lab  -  Scale  -  Drug  -  Dosage MG  - PCR
2010/Jul -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 1.2%
2010/Oct -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0.25%
2010/Dec -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0.367%
2011/Mar -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0.0081%
2011/Jun -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0%
2011/Sep -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0.00084%
2011/Dec -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0%
2012/Mar -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0.004%
2012/Jun -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0%
2012/Sep -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0%
2012/Dec -  MSKCC  -  Non-IS  -  Sprycel  - 100 - 0%
2013/Jan -  Quest  -  IS  -  Sprycel  -  50-60-70  - 0%
2013/Mar -  Quest  -  IS  -  Sprycel  -  60-70  - 0%
2013/Apr -  CUMC  -  Non-IS  -  Sprycel  - 50 - 0.036%
2013/May -  CUMC  -  Non-IS  -  Sprycel  - 50 - 0.046%
2013/Jun -  Genoptix  -  IS  -  Sprycel  - 50 - 0.0239%
2013/Jul -  Genoptix  -  IS  -  Sprycel  - 70 - 0.0192%
2013/Jul -  Genoptix  -  IS  -  Sprycel  - 70 - 0.0034%
2013/Oct -  Genoptix  -  IS  -  Sprycel  - 70 - 0.0054%
2014/Jan -  Genoptix  -  IS  -  Sprycel  - 70 - 0.0093%
2014/Mar -  Genoptix  -  IS  -  Sprycel  - 100 - 0.013%
2014/Apr -  Genoptix  -  IS  -  Sprycel  - 100 - 0.0048%
2014/Jul -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2014/Nov -  Genoptix  -  IS  -  Sprycel  - 100 - 0.047%
2014/Dec -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2015/Mar -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2015/Jun -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2015/Sep -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2015/Dec -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2016/Mar -  Genoptix  -  IS  -  Sprycel  - 100 - 0.0228%
2016/Jun -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2016/Sep -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2016/Dec -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2017/Mar -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2017/Jun -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2017/Sep -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2017/Dec - Genoptix  -  IS  -  Sprycel  -  100 - 0%


#7 9miler


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Posted 12 October 2011 - 01:48 PM

Thank you again. This makes sense. This is where I will begin the discussion with my new oncologist. He comes very highly recommended, so I believe he will be amenable to my requests. 9

#8 hannibellemo


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Posted 12 October 2011 - 04:00 PM


I go to the Mayo Clinic in Rochester and they tend to do the FISH until you reach CCyR (0%). Then they switch over to PCR. It really does make sense as when we are first diagnosed our PCR percentage is generally very high and doesn't tell us a whole lot either but it certainly can raise anxiety levels in many of us.

After reaching CCyR a PCR was done every 3 months until I reached MMR and then it was stretched out to every 6 months. This is a very expensive test, I can't imagine too many insurance companies agreeing to pay for one every 6 weeks. That seems excessive to me.

I think your new onc is doing the prudent thing for you.  Good luck and be sure to let us know when you hit your milestones - Complete Cytogenic Response (CCyR), Major Molecular Response (MMR) and Complete Molecular Response (CMR or PCRU, the U stands for undetectible). Don't worry if you never or are slow to reach PCRU, not everyone does.

Also,  Mayo uses the International Scale which is more of an equivalency for log reductions with .02% on the IS being CCyR and .01% MMR. I didn't catch that you were dxed 5 years ago. You should get a pretty good idea where you stand with your PCR now - can you tell us what your most recent test said? If you haven't reached CCyR or MMR at this point I would want to know why and question whether a drug change might not be in order.




"You can't change the direction of the wind but you can adjust your sails."

DX 12/08; Gleevec 400mg; liver toxicity; Sprycel 100mg.; CCyR 4/10; MMR 8/10; Pleural Effusion 2/12; Sprycel 50mg. Maintaining MMR; 2/15 PCRU; 8/16 drifting in and out of undetected like a wave meeting the shore. Retired 12/23/2016! 18 months of PCRU, most recent at Mayo on 7/25/17 was negative at their new sensitivity reporting of 0.003.<p>

#9 matt92711


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Posted 12 October 2011 - 04:05 PM

There is one more thing I could think of that apparently applies to a significant number of patients. If you are not taking 90%+ of your doses of Gleevec it is much less likely you will ever see a MMR or CMR. Even CCyR is much less likely if you are missing doses. 90% means missing 3 daily doses a month or more. Some study I saw showed something like over 90% of patients on Gleevec who took at least 90% of doses had optimal responses whereas those who did not take 90% of doses had a much lower rate of CCyR (somewhere in the 70th percentile). Further none of them acheived a CMR. If this applies to you this would be the first thing to fix, if side effects are causing you to miss doses you can talk to your doctor about over the counter medicines to counter them or you could try switching drugs.

#10 noelani


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Posted 12 October 2011 - 04:28 PM

Can you remember where you saw the study?. My husband was on Gleevec 3 months, and now has been off almost 3 months because his platelets just wont come up to 75. I'm very concerned about this. The doctor says we just have to wait for him to go back on medication. We are going to have Dr. Shah at UCSF give us another opinion.

#11 Pin


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Posted 12 October 2011 - 06:10 PM

Hi there,

I read this paper with interest as well:


There might be more, but that's the one I read.

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

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