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Change of Sensitivity Parameters for BCR/ABL Tests


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#21 Trey

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Posted 08 June 2017 - 03:26 PM

What does limit quantification of 0.0069% mean?

 

Limit of quantification means the limit of reporting, which for your lab is -4.5 logs.  But most PCR equipment/reagents can detect far below that, probably to -7 logs.  So "limit of quantification" actually means the point at which the results are truncated and no longer reported due to false positives concerns, so it is not a limit of detection.  The limit of quantification is a mixture of how low the PCR can detect tempered by where the reporting should be cut off since false positives rise exponentially below about -4.5 logs. 

 

PCRs were not invented to detect leukemia in people.  They were invented to detect bacteria in foods.  Think of it that way and you will no longer be tempted to expect such surgical precision from these tests.


Edited by Trey, 08 June 2017 - 07:55 PM.


#22 scuba

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Posted 08 June 2017 - 03:46 PM

An interesting point of fact on the invention of PCR:

 

http://bitesizebio.c...vention-of-pcr/

 

"Mullis received the Nobel Prize for his ground-breaking invention in 1993. He also received a $10,000 bonus from his employers, Cetus, who later sold the patent rights to Hoffmann La-Roche for a cool $300,000,000. Seems to me there's a lesson in there somewhere..."


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"


#23 Kali

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Posted 08 June 2017 - 03:58 PM

Thanks Trey,

That is a very helpful explanation of how to better understand these tests.

It was somewhat confusing. When I would read talk of logs on here, I didn't how to equate that to my PCR test. What you shared helps it make more sense.

Diagnosed June 2014. WBC 34.6 and Platelets 710 at diagnosis. Bone Marrow Biopsy pre-op diagnosis: Leukocytosis. Post-op diagnosis: the same, Leukocytosis. No increase in blasts <1%. Quantitative BCR/ABL testing and formal chromosome analyses confirmed CML diagnosis.<p>Supplemental Report: Abnormal BCR/ABL1 FISH result t(9;22). Molecular test for BCR/ABL1 fusion transcript by RT-PCR positive for BCR/ABL1 transcripts, b3a2 at 133.561% and b2a2 at 0.001% and ela2 at 0.001%. Followup monitoring showed negative for ela2. BCRABL1 was 148.007 at diagnosis. Started Sprycel 100 mgm and blood work was normal at 3 weeks. MMR at 3 months: 10/4/14 was 0.106. Stayed in that range with one dip to 0.04 once and back to 0.1 range. Oct. 2015, BCRABL1 was not detected, following with 0.0126, 0.0092, <0.0069, 0.0000, <0.0069, 0.0000. Now on 70 mgm of Sprycel. Continuation of PCR test results: 07/07/2017, 0.0000%, now on 50 mgm of Sprycel, PCR 9/12/17 0.0074%, PCR 11/3/17 0.0000%, PCR 1/17/2018 0.0000%


#24 cmljax

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Posted 09 June 2017 - 06:43 AM

I am still confused.  My last 2 PCR results said the following:

 

Positive. BCR/ABL1 p210 mRNA transcripts were detected at a very low quantitative level (<0.003% of total ABL1 (%BCR/ABL1(p210):ABL1).

 

So given what Trey said, is it possible that my last 2 positive results were actually false positives and could have been negative?  Do some labs report positives below the "limit of quantification" as negatives or do they all report it as positive at a very low quantitative level?


Dx 9/26/16 WBC 28800; platelets 749; FISH 97% PCR 43%

Tasigna 600MG per day

October 2016                     PCR 22% IS

November 2016                 PCR 5.8% IS

December 2016                 PCR 0.1% IS  MMR!!

March 10, 2017                 PCR 0.006% IS  MR 4.22

Tasigna 450MG per day

April 5, 2017                      PCR <.003% IS

June 5, 2017                     PCR <.003% IS (dose reduction validated!!!)

Tasigna 300MG per day starting June 15, 2017

6-day drug break starting June 20, 2017 due to multiple AE's

July 24, 2017                     PCR <.003% IS

September 18, 2017          Negative, AKA PCRU

Tasigna 150mg per day starting 9/18/17

October 30, 2017               Negative

December 11, 2017           Negative


#25 Trey

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Posted 10 June 2017 - 08:34 AM

The PCR cut-off is arbitrary, and is different at various labs.  A few still go down to -5 logs, last I knew.  If the positive detection is slightly below the cut-off, then it is probably not a false positive.  But since they do not provide your actual number, only "less than .003%" that is not very useful.  But if a lab has a cut-off, I don't know why they still report the positives unless someone is in a cessation trial, then that might be a reason for clinical trial purposes. 



#26 hannibellemo

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Posted 30 July 2017 - 01:30 PM

Just had my annual checkup at Mayo. My onc wasn't even aware that the sensitivity reporting had changed! However, he verified it for me when my PCR results came back that afternoon. Happy to report that I'm still negative even at the new reporting level!


Pat

 

"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>


#27 M.A.

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Posted 30 July 2017 - 07:45 PM

What great news Pat. So glad to hear you have retained PCRU for 18 months on 50mg. I hope you are enjoying your retirement :)


CML diagnosed April 2016

Type One Diabetes diagnosed April 1980 (age 12)

 

BCR-ABL (IS)

46.77  April 2016

3.568  July 2016  

0.076  Oct 2016

0.016  Feb 2017

0.0079  April 2017

0.014  July 2017

0.019  Sept 2017

0.011  Nov 2017

0.019  Jan 2018

 

Sprycel

100mg April 29 - September 22

75mg  September 23 - October 28

50mg October 29 2016 to present


#28 hannibellemo

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Posted 31 July 2017 - 06:52 AM

Thanks, M.A. I highly recommend retirement, although I could make some suggestions for change. I think we should be happy and carefree when we are young so we have both the time AND energy, and then go to work when we are middle aged and are no longer quite so energetic.   ;)


Pat

 

"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>


#29 kat73

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Posted 31 July 2017 - 11:19 AM

Great news, Pat - you are my "role model," for 50 mg, no more pleural effusions, and . . . PCRU!

 

I agree, and I wish I could go to college NOW instead of when I was 18.  All that time for reading and 3 square meals a day provided by somebody else.  I would most certainly go to class this time around. :D


Dx July 2009 on routine physical.  WBC 94.  Started Gleevec 400 mg Sept 2009.  MMR at 2yrs.  Side effects (malaise, depression/anxiety, fatigue, nausea, periorbital edema) never improved.  Kidney issues developed because of Gleevec.  Switched to Sprycel 70 mg in Aug 2011.  Above side effects disappeared or improved.  Have been MR3.5 - 4.5 ever since.  Two untreated pleural effusions followed by one treated by stopping Sprycel Jan 2017.  After 9 weeks, PCR showed loss of MMR; re-started Sprycel at 50 mg and in 3 months was back to <0.01% IS.  Pleural effusion returned within a couple of months, same as before (moderate, left side only).  Stopped Sprycel 50 mg for 12 weeks; pleural effusion resolved.  At about a monthoff the drug, PCR was 0.03; at 11 weeks it was 2.06 - lost CCyR? Have returned to 50 mg Sprycel for 3 weeks, intending to reduce to 20 mg going forward.





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