Blog post on PCR Confusion

May 25, 2010

PCR Confusion – A CML Patient's Perspective

By Trey Fox | May 18, 2010

http://www.cancernetwork.com/blog/display/article/10165/1570782

Polymerase Chain Reaction (PCR) testing for BCR-ABL has become the primary

method used to monitor leukemia levels in CML patients. As a CML patient for

almost 5 years, and someone who is in regular contact with other CML patients

from around the world, I continually see the confusion that surrounds this very

important issue. We hang on every PCR test result, since it shows our response

to CML drugs or lack of response. Our progress is tied to PCR numbers and log

reductions. The ultimate goal for us is an undetectable PCR & #8213; we live for

the results, celebrating if the numbers drop, and becoming discouraged if they

increase, no matter how small. Yet, with all the importance tied to the single

test, the PCR is also a source of confusion for most CML patients, and it is

getting worse, not better.

The confusion regarding the PCR test results stems from several sources.

First, each lab uses slightly different procedures, equipment, and standards,

which can affect PCR final results. So PCR numbers from different labs cannot

be directly compared. This is a source of confusion when an oncologist uses

different labs, when we change physicians, or when we see a specialist who uses

a different lab. How do we know whether we are progressing or regressing?

Sometimes our oncologist does not sufficiently understand this inter-lab

variation, and becomes alarmed when the results from one lab show an increase

from the previous results from another lab. This problem has been well

documented, and led to the development of the PCR International Scale concept.

The PCR International Scale was supposed to reduce PCR confusion by

standardizing PCR results around standard log reduction levels. But as labs are

in the middle of this changeover & #8213;and many US labs are not

participating & #8213;this PCR confusion has been increased by the very method

that was supposed to make reporting simpler.

Recently a CML patient was told she was failing Gleevec therapy because her PCR

increase by more than one log. When the story was sorted out, her PCRs had been

done by different labs, and only the more recent PCR result was on the

International Scale, and that number was much higher. But the oncologist did not

understand this change in PCR methodology and instead of providing a log

reduction comparison simply compared the PCR numbers, and assumed she was

failing drug therapy. So the patient was unduly alarmed by the higher number

until a fellow CML patient pointed out the misunderstanding through a CML

discussion board.

Another CML patient saw his PCR result increase by more than one log, and his

Onc did not initially realize that the lab had changed over to the International

Scale, which for this lab increased the PCR numbers significantly. The

International Scale has also introduced interesting factors, including PCRs

higher than 100%. Terrific.

Other sources of PCR confusion continue unabated. Since a PCR is a

sophisticated and complicated estimate, the results can fluctuate. A PCR test

could be done twice on the same tube of blood and different results would likely

occur. Some labs say that a PCR is only accurate to within approximately 1/3

log, so although PCR results are out to five significant digits, they are not

really that precise.

There are many variables, the most significant being time from blood draw to

actual PCR testing. If a PCR is done immediately after blood draw it will be

higher than if the test is done 24 to 48 hours after the draw. A false-negative

PCR can result from a spoiled sample, and 48 hours is the standard cut-off for

many labs, but even then the sample will have degraded by possibly 50%. I

learned the hard way not to have a PCR done late in the week. Most labs do not

work weekends, so the sample could easily spoil before the lab tests it on

Monday.

There are still more sources of confusion. Most PCR reports express the result

as a percentage ratio of BCR-ABL to a control gene. But some report PCR results

as non-percentage scientific notation numbers, and others simply report a raw

PCR number without reference points.

The ultimate goal for the CML patient is to reach the PCR undetectable level,

whereby the PCR test finds no leukemic cells in the sample. But not all PCR

tests have equivalent sensitivity. So some patients are PCR undetectable using

less sensitive PCR testing, while others with deeper responses remain PCR

detectable by more sensitive equipment.

PCR results are best used when viewed over time. Longer term trends are more

important than an individual PCR result. But that can be difficult to remember

when your PCR result rises. So the PCR test is both highly important to CML

patients and also a source of great confusion. This is a serious issue since

the PCR is a vital tool in determining response to drug therapy, and therefore

our treatment options.

May 25, 2010

Thank you Pat for this valuable information.

How is the weather in phoenix now, did it start to warm up. -t is in the 90

degree here in Florida not mention humidity. Thank you again Pat and GOD bless

T

Sent from my Verizon Wireless BlackBerry

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