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BMB PCR does not match Blood PCR - ????


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#1 gianfranko

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Posted 04 May 2011 - 01:22 PM

So, my girlfriend just got back her BMB PCR results and the ratio that was reported was 0.515.  Earlier she got a PCR-U result from blood so I don't understand this.

The complete results so far:

@diagnosis: ratio 3.234 log reduction 0.106

@2.5months treatment: ratio 0.095 log reduction 1.638

@5months treatment: ratio 0.008 log reduction 2.713

@8months treatment: log reduction 2.5

@12months treatment: PCR-U

@12months, 11days: ratio 0.000167, no log reduct (from Moffit, different lab than previous results)

The above were all done from blood.

Then:

@13months: BMB done and sent to do PCR and FISH:

     PCR ratio: 0.515 (from Bone marrow; first time done)

     FISH: awaiting results (from Bone Marrow)

Results just dont make much sense to me.

Anyone experienced this before?



#2 CallMeLucky

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Posted 04 May 2011 - 03:44 PM

My PB vs. BMA PCR was also different with the BMA being higher 3 months later, but not by that much.  Studies claim they are equally accurate, but I have my doubts.  I'm mentally preparing myself for my June visit when I have another BMA.  I'm expecting my PCR to up tick again.

Here's my history

7/7/2010PB1.2
10/25/2010PB0.25
12/13/2010BM0.367
3/14/2011PB0.008

My doctor said as long it doesn't move an entire log, then she interprets is as a variance in the test.  In your girlfriend's case it seems like a bigger jump.  I don' t know what to make of that.  I just wanted to show you that my PCR ticked up, slightly, 3 mo later when they drew BMA.

For comparison, here are my FISH results

Appointment   DateSpecimenSample SizeResult
7/7/2010PB500490
10/25/2010PB50025
12/13/2010BM5003
3/14/2011PB5000

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%
 

 


#3 gianfranko

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Posted 04 May 2011 - 04:03 PM

I am not sure what to make out of it.  It just doesn't make any sense.  If we believe the numbers to be true then that means that the BCR-ABL/ABL went from

1/10,000 to 1/2 in 19 days.

Your results, on the other hand, make much more sense.

FISH should come out early next week.  Hopefully that can shed more light into the situation.



#4 gianfranko

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Posted 04 May 2011 - 06:36 PM

I have written an email to the CML specialist in Moffitt.  Hopefully he can provide some insight as to what is happening.  Problem is that we are in Palm Beach County and he is in Tampa and we cannot just drive there anytime in the near future (for a couple of weeks).

I am hoping he gives us some info over the email.

Her current oncologist has said to change nothing and her next appointment is in June.



#5 Trey

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Posted 04 May 2011 - 09:04 PM

I would want to do another blood PCR right away to cross check the results.



#6 gianfranko

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Posted 04 May 2011 - 10:03 PM

Trey wrote:

I would want to do another blood PCR right away to cross check the results.

Yes, this is something that we are also thinking about.  We are just waiting on the results from FISH (early next week) and then making a decision.

Here is what the CML specialist from Moffitt replied to us:

"I think the FISH/cytogenetic should be important in this situation.

I reviewed all the labs and although sometimes is hard to make comparisons between BM and PB I will have to say that it seems that the ratio keep increasing from a previous level obtained in September 2010.
Technically by this level of PCR we should see some positive cytogenetics and if this is confirmed we will be dealing with a relapse.

Don't panic though, sometimes PCR can be very tricky. The last negative PCR done on 3/28 does not make sense and was possibly a false negative.
A kinase domain mutation should be done and I will also recommend another PCR in PB done by quest.

As I told you we can't compare between labs but when you can by we can repeat it again and see any trend with our PCR."

The 03/28 results he refers to is the PCR-U results (12months results from Quest Diagnostics).

Personally I think the 03/28 results agrees with the Moffitt PCR results and that this new result is the aberrant one.



#7 gianfranko

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Posted 04 May 2011 - 10:05 PM

Trey,

Do you think we should not wait for FISH results and directly go ahead with a new blood PCR?

What is the urgency in this type of situation?



#8 Trey

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Posted 05 May 2011 - 08:56 AM

Waiting a few more days won't be an issue.  The specialist's reply seems exactly right.



#9 gianfranko

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Posted 09 May 2011 - 12:43 PM

So, I have some news to report:

The FISH results:

The local doctor just told us "everything is normal".  Since this was kind of vague to me, I went to pickup the test results.  Basically they say: "MPN FISH: NORMAL results, Metaphases counted: 20, metaphases analyzed: 20, Metaphases karotyped: 3, Banding Technique: CPG, Banding Resolution: 400, INTERPRETATION: Cytogenetic analysis reveals a NORMAL female karotype without apparent clonal aberrations"

Thus, I take it this just means there were no leukemic cells found (i.e. no 9&22 fusion chromosome).  Moreover, these results are coming from a company called Genoptix.

The PCR results:

These results are coming from the same company as above, Genoptix.  Why the did the doctor sent out the BM to another company?  Not sure...

But the important thing is that over the phone they told us the result was "0.515" but that is actually a percentage; meaning it really is a 0.00515 ratio.  They also report that in their lab a 3 log reduct is referenced by 0.079% - meaning that right now we have to go 6.5X lower to get to MMR by this lab.

So basically results now are looking like:

@diagnosis: ratio 3.234 log reduction 0.106

@2.5months treatment: ratio 0.095 log reduction 1.638

@5months treatment: ratio 0.008 log reduction 2.713

@8months treatment: ratio 0.011 log reduction 2.5

@12months treatment: PCR-U

@12months, 11days: ratio 0.000167, no log reduct (from Moffit, different lab than previous results)

The above were all done from blood.

Then:

@13months: BMB done and sent to do PCR and FISH:

     PCR ratio: 0.00515 (from Bone marrow; first time done; from a third lab different from two above)

     FISH: negative, 0%

So, in conclusion - are these results okay?  We went from a CMR by the first lab to not even MMR in the last lab



#10 Trey

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Posted 09 May 2011 - 08:03 PM

Overall the news is good that the FISH remains negative.  I would want to see the next PCR to make sure the trend line has not been broken, since it is not clear from these results which way things are going.  I doubt the PCRU was accurate a few months ago.  But nothing to get worked up about in these results.



#11 gianfranko

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Posted 10 May 2011 - 01:41 PM

Trey,

In your past experience, with your own results, did you also saw an increase in PCR results similar to what Lucky reported?  His PCR is going up in the BM eventhough the FISH is going down in December compared to his October results



#12 Trey

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Posted 10 May 2011 - 08:06 PM

The peripheral blood has a "leveling" effect on the PCR and blood counts in general.  The marrow is a wild and crazy place, and cell production does not go in a straight line.  There are growth spurts and sudden blast increases then sudden drops.  A snapshot of one moment in time of the marrow can be deceiving.  So the blood is actually a better place to do PCRs for residual disease monitoring.  And if CCyR has not been reached, the FISH is more generally more accurate than PCR, although an occasional lab error can occur with any test.  It has often been said that blood follows marrow, but that is only true to a point.  The leveling effect that occurs in the blood needs to be considered, and a truer picture of long term trends will be found in the blood.

CCyR (zero FISH) is a good place to be.  We often forget that in this era of PCRs.






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