8 replies to this topic

[BPilgrim]

Hi all.

I was dx with CML twelve years ago and have been on Gleevec for about ten years.  I spent the first nine years on Gleevec as PCRU, but in January, I got a "positive" result on my quant BCR/ABL1, major test.  The report stated: "fusion transcripts detected, but below the limits of quantification for assay...so BCR/ABL1 to ABL ratio cannot be calculated."

My next two PCR tests (all with the same lab) returned to PCRU.

However, my most recent September test again returned a positive result, this time the lab calls it a "weak positive", which may just be a terminology change at the lab.  The result again mentions the result being below the limits of the test, so no ratio is calculable.  But the report now adds "The result on the International Scale is <0.0069%".

I am wondering about that <0.0069%.  If my previous tests were 0.000 PCRU, how does a lab come up with a bcr/abl fusion that's detectable but below their quant limit, and still report the <0.0069%?  What is the pathologist seeing?

Maybe it's also worth noting that my January test was done with a 1 in 100,000 detection limit, but the Sept test done with a 1 in 125,000 limit.

Of course, I am trying to figure out what the result means regarding my disease.  I went nine years PCRU and suddenly start jumping in and out of weak positives.  Does this indicate resistance to Gleevec?  Or is it a product of more increased sensitivity in the PCR testing?

What causes the jumping around, and does the jumping around affect my standing on the 'relapse prediction' chart for patients on Gleevec?  (The one that says if you've been in PCRU for x many years, then your chance of relapse is y%)

I'd be grateful for any insight.

Thanks.

[Trey]

First, you describe a change in PCR processes at your lab.  They have obviously changed equipment or reagents or both, which has increased sensitivity.  Most labs that advertise 1 in 100,000 are really closer to 1 in 1 million.

The weak positives would not be a welcomed change, but they do not clearly show loss of response, resistance, etc at this point.  You could be at the same level as previously, with the lab sensitivity increased.

I assume you have been taking your drugs as prescribed?  If so, it is odd that you would show as positive since the long term should be a continually decreasing trend, even if undetectable.

[BPilgrim]

Yep, I take my 400mg every evening like my life depended on it...only missed 3 days in ten years.

Are there other patients who've been PCRU for many years on Gleevec, but suddenly/occasionally get a positive result, only to go back to PCRU again?

I've noticed some people post lab results of 0.0015% or 0.0027%, for example.  My lab says they are not 'validated' to give specific results below 0.0069%, hence their generalized 'less than' symbol with <0.0069%.  But does that mean the other patients' labs are performing more accurate/better tests?

Is there a CML'er consensus on the best Quant PCR labs?

[valiantchong]

The chances of being PCRU for 10 yrs  and then being resistance is extremely low. I think the trend of weak positives are needed to verify resistance rather than 1 result showed weak positive. May be you could try a second lab for verification. I think PCR lab measurement erorr do occured within 0.5 to 1 log, but than again a trend of weak positive is needed to verify for for resistance.. Well since you are got this from the doctor office, could you share what the doc say ?

[PhilB]

I wouldn't worry too much about that incredibly specific looking 0.0069% number.  They'll have taken a nice round number in their raw data (say 1 in 100,000 or 1 in 125,000) and then multiplied it by their international scale conversion factor and printed the result.   This is one of my (many) mathematical pet hates and happens all the time.  A typical example would be when someone say estimates a distance as 2 miles and then some idiot then converts it to metric and quotes it as 3,219 metres suggesting a completely spurious level of accuracy.

All they are really saying is:

1. Your test is below the limit at which we can give a number; and
   
2. The limit at which we can give a number is just over a 4 log reduction IS
   

You're right that many labs seem to report numbers down lower, but only by about another log.

[Susan61]

Hi:  I hope it was just some sort of glitch with the lab equipment for you.  You have had CML as long as I have.  I was diagnosed 13 years ago this Dec., and have been PCRU for 8 years.  I am also on 400mg. of Gleevec.  I have had so many people tell me that I am probably cured, and to stop the Gleevec.  I just refuse to do that, and then I see your posting with questions on if your holding your PCRU level.

     Maybe you should try another lab to see what they get.  You said its the same lab running your test.  I have always been with Quest Labs, and due to insurance I have to stay with them.  I do not know if that is your case also, or if you can get one done at another lab for comparison.

Your probably fine after being PCRU all this time.  Please let us know how your doing.  I will say a prayer that it was a problem with the Lab and not your Blood.

Susan

[BPilgrim]

I am going to repeat the test in three weeks.  My doc thinks the "weak positive" result is due to PCR tests themselves becoming more sensitive.  He says he would only become concerned if he saw a continuing upward trend in the percentages.  I'll post when I get my results in five weeks or so.

Thanks everybody!

[Susan61]

Hi:  I wish you the best on your repeat testing, and pray you tell us its a PCRU.  I know its hard, but I know so many people who have never gotten to PCRU, and have had CML for over 13 years.  Maybe that will keep you thinking Positive.

Susan