25 replies to this topic

[jmoorhou]

I know I should know this..

[Calvink669]

PCRU = CMR = complete molecular remission = cml is undetectable with the most sensitive forms of testing.

Doesn't mean cured, but one can assume that a person without disease or one that has indeed been cured would be PCRU on any given PCR test.

So remaining PCRU is the best possible scenario there is.

[jmoorhou]

Thank you!  

[tiredblood]

Since I've been PCRU the results on the PCR have been 0.000%, but my hematologist/oncologist said you could get a result of 0.0000% (4 zeros to the right of the decimal).  IOW, no abnormal cells detected in like a million cells or something.

[scuba]

Since I've been PCRU the results on the PCR have been 0.000%, but my hematologist/oncologist said you could get a result of 0.0000% (4 zeros to the right of the decimal).  IOW, no abnormal cells detected in like a million cells or something.

 

PCR results reported beyond the second decimal place are meaningless (0.XX%). The error is too great and false positives are recorded at that level.

 

PCR does not "detect" cells. PCR is a measure of RNA protein expression which is believed to be unique for CML. So technically one has to have a CML cell somewhere making proteins unique to CML. The problem is that test results below 0.00x... can provide erroneous results.

 

M.D. Anderson, for example, does not report results below 0.00. They just report either "undetected" or "low positive" with PCR < 0.01%.

 

A terrific result is anything equal or below 0.1% PCR. It is at this level that a patient is inferred to have one in a million CML cells - very low. That is the definition of MMR. Another log lower (0.01%) and you are at the limit of the tests sensitivity with very low residual CML disease. At numbers reported as 0.00x - that is just noise and truly meaningless.

[Widgeonus]

PCR results reported beyond the second decimal place are meaningless (0.XX%). The error is too great and false positives are recorded at that level.

PCR does not "detect" cells. PCR is a measure of RNA protein expression which is believed to be unique for CML. So technically one has to have a CML cell somewhere making proteins unique to CML. The problem is that test results below 0.00x... can provide erroneous results.

M.D. Anderson, for example, does not report results below 0.00. They just report either "undetected" or "low positive" with PCR < 0.01%.

A terrific result is anything equal or below 0.1% PCR. It is at this level that a patient is inferred to have one in a million CML cells - very low. That is the definition of MMR. Another log lower (0.01%) and you are at the limit of the tests sensitivity with very low residual CML disease. At numbers reported as 0.00x - that is just noise and truly meaningless.

What I don't understand is a doc at MD Anderson told me that the conversion from their standard to International Standard is approximately .35, so wouldn't .1% at MD Anderson be .035 IS which is way under MMR?

[Trey]

Wid,

The MD Andeson PCR conversion is not exactly clear.  But if their conversion factor really is .35, then that is correct.

 

[NOTE: this info was revised to avoid confusing people due to later discussions below]

 

A .35 conversion factor at MD Anderson is quite a variation.  For example, OHSU (Portland, OR) has a 2.22 PCR IS conversion factor, so for OHSU:  2.22 X [PCR Raw %] = IS percentage    So if the OHSU PCR result is .045%, that is equal to .1 IS.  This means that OHSU MMR is .045% instead of the International Scale .1% MMR

Edited by Trey, 03 January 2015 - 10:52 AM.

[scuba]

Wid,

The MD Andeson PCR conversion is not exactly clear, but if the conversion factor relates to .35 it most likely means the .35 is NOT the conversion factor (way too large) but rather the bias from the International Scale (IS) norm.  That bias is converted into an anti-log bias which for .35 is 2.22, which is the actual conversion factor.  The 2.22 conversion factor is then multiplied to the lab PCR % value to convert to International Scale.  This also determines where the CCyR, MMR, etc are located for this lab.  OHSU has a known .35 bias, which means they use 2.22 as their conversion factor; so if MD Anderson is telling you they have a .35 difference, this means they would need to use 2.22 as their PCR conversion factor as follows:

 

2.22 X [PCR Raw %] = IS percentage

 

So for example, if an MDA PCR result is .045% :

2.22 X .045  = .1 IS

 

This means that MD Anderson MMR is probably .045% instead of the International Scale .1% MMR

 

 

I will send Dr. Cortes a note to re-confirm.

 

Dr. Cortes reply:

"Levels of 0.1 or less in IS is MMR. An MDACC level of 0.28 is equivalent to 0.1 in IS." 

 

You had it backwards, Trey. No worries, you probably still are hung over from New Year's celebration.

Edited by scuba, 02 January 2015 - 12:13 PM.

[Widgeonus]

I will send Dr. Cortes a note to re-confirm.

Dr. Cortes reply:
"Levels of 0.1 or less in IS is MMR. An MDACC level of 0.28 is equivalent to 0.1 in IS."

You had it backwards, Trey. No worries, you probably still are hung over from New Year's celebration.

That makes me feel much better since I'm at .08 MD Anderson scale.

[Trey]

That is even more odd than I suspected.  If MDA knows what its conversion factor is, then why don't they use it to convert PCR values into IS log reductions for their patients?  Wid and others have been left guessing about their real PCR status -- that is not how a world-class cancer center acts.  That is bizarre.

Edited by Trey, 02 January 2015 - 09:08 PM.

[scuba]

That is even more odd than I suspected.  If MDA knows what its conversion factor is, then why don't they use it to convert PCR values into IS log reductions for their patients?  Wid and others have been left guessing about his real status -- that is not how a world-class cancer center acts.  That is bizarre.

 

I suspect because the conversion factor is not one to one. The conversion factor is an approximation. PCR analysis, as you know, is based on making multiple copies of DNA segments and then "incubating" them so that copies can be grown using primers. The way this is done is not standardized. An attempt was made to standardize this (so called International standard), but M.D. Anderson, for whatever reason, does their own thing. Over time, they note that there is a "rough" correlation that their results correspond to I.S. results at the .35 factor level. So it is a rough comparison, but it is not scientific.

 

I do know this, however  ... when I gave my first results, done by a different lab, to M.D. Anderson to include in my file, they refused. Dr. Cortes, himself, told me that he has been "burned" (his words) using results from other labs not his own when treating patients. He strongly believes in MDACC PCR lab testing methods and results.

 

Given the fact that his guidance (reduced dosage for treatment and other protocols) has enabled me to get to "undetected" (so far) with only 20mg. Sprycel, I will give him benefit of the doubt.

 

It's not the cancer center that's important. It's your doctor. There probably is a "rough" correlation, though,  between how good your cancer center is and the doctor who chooses to associate with it.

 

Happy New Year

 

Michael

[Billie Murawski]

HUH!!!

[Trey]

In other words, MDA does not want their patients to understand their treatment progress.  Too mysterious for those silly patients to understand such things.  Billie inadvertently uttered the correct response which is "HUH!!!". 

[scuba]

In other words, MDA does not want their patients to understand their treatment progress.  Too mysterious for those silly patients to understand such things.  Billie inadvertently uttered the correct response which is "HUH!!!". 

 

Yep. 

[Antilogical]

I am being treated at a major cancer center in Pittsburgh. They use their own control gene standard in their PCR reporting, too.  During a recent visit, I whined about it to my doctor.  Lo and behold, the next result came in with both the local number and the IS number.

[Billie Murawski]

In other words, MDA does not want their patients to understand their treatment progress.  Too mysterious for those silly patients to understand such things.  Billie inadvertently uttered the correct response which is "HUH!!!". 

Trey,

I did not inadvertently utter the correct response HUH!!! I knew what I was doing I had absolutely no idea what you guys were talking about, I saw an opening for a 3 letter word and I typed huh.  Billie

[Widgeonus]

What's bad is that I didn't realize until recently about the conversion factor. If I had, then I would have known that I reached MMR in about 3 months instead of when I got to .09 MDA standard at 12 months. Either way, it is a good response, but now I know it was better than what I originally thought. Oh well, I'll just keep on keepin on.

[scuba]

What's bad is that I didn't realize until recently about the conversion factor. If I had, then I would have known that I reached MMR in about 3 months instead of when I got to .09 MDA standard at 12 months. Either way, it is a good response, but now I know it was better than what I originally thought. Oh well, I'll just keep on keepin on.

 

When it comes to PCR it really is about trend and nothing more. If your trend is down and you cross the 0.1% threshold regardless of what scale is used - you are going to survive CML and die of something else. This is important for people to understand. Too many of us get fixated on the numbers when the test itself is prone to so much error (a factor of 10 or one log) and variability. The reality is that FISH is more important in telling you disease level and significance. How long it takes for FISH to fall to zero is more a measure of disease resistance to treatment than anything else. Once Fish = zero and is maintained, PCR is really only important as the canary in the mine shaft. Long term trends up or down are what's meaningful - and by a log or more. And then only for a couple of decimal places.

 

In my case, I just achieved a PCRU level for the first time. But I have no expectations that I will be PCRU when the next test results come in. All I care about is if the number has changed by more than a log and then I would need to see another test (by the same lab) to confirm.

[scuba]

When it comes to PCR it really is about trend and nothing more. If your trend is down and you cross the 0.1% threshold regardless of what scale is used - you are going to survive CML and die of something else. This is important for people to understand. Too many of us get fixated on the numbers when the test itself is prone to so much error (a factor of 10 or one log) and variability. The reality is that FISH is more important in telling you disease level and significance. How long it takes for FISH to fall to zero is more a measure of disease resistance to treatment than anything else. For the vast majority of us, we achieve FISH = zero very quickly once we find the correct drug and correct dose. Once Fish = zero and is maintained, PCR is really only important as the canary in the mine shaft. Long term PCR trends up or down are what's meaningful - and by a log or more. And then only for a couple of decimal places.

 

In my case, I just achieved a PCRU level for the first time. But I have no expectations that I will be PCRU when the next test results come in. All I care about is if the number has changed by more than a log and then I would need to see another test (by the same lab) to confirm.

[Trey]

It is more than trend.  A response must be adequate based on trend plus overall PCR levels.  A patient needs to know if they have responded well enough on the current drug, and overall PCR numbers and log reductions are key to that.  A slow decrease trend at high PCR levels may not be adequate, so a drug change is often required.  The patient needs to understand this to know the status as an informed patient.  That is what is appalling about what MD Anderson is doing with regard to PCR information and keeping patients in the dark.  Even you Michael had very high PCRs from MDA, and if you had known that the conversion was that significant it would have made you understand your response was better then you had thought at the time.  And Wid was unnecessarily concerned that his PCR was higher than he thought it should be, when all along he was in much better shape.  That is poor practice by MDA.