9 replies to this topic

[LivingWellWithCML]

Hi,

Just got my 15 month PCR results (Gleevec 400mg) and Emory changed up their PCR to International Standard.  In addition to standardization, does this generally translate to increased sensitivity as well?  In looking at the report, it measures sensitivity differently than my previous test.  Is this considered to be a high level of sensitivity as compared to other PCR machines/methods out there?

• "Limit of detection = 0.0051 copies of transcript per mL" (The test was run against a 4 mL PB sample)

And sure enough, I'm back into the detectable zone again with PCR = 0.043% IS.  The trend is what matters (I know), but it's kinda tough to keep your head up when you see a positive result after having a negative result with the previous test, so I'm trying to justify this as a sensitivity increase at Emory.  Anyway, what am I looking at here; ~ 3.5 log reduction?

Thanks for your feedback, everyone -

[CallMeLucky]

Dan,

I can relate, below is my PCR history

Date	Percentage	Decimal	Personal Log Reduction
7/7/2010	1.20000%	0.0120000000	-
10/25/2010	0.25000%	0.0025000000	0.6812
12/13/2010	0.36700%	0.0036700000	0.5145
3/14/2011	0.00810%	0.0000810000	2.1707
6/13/2011	0.00000%		4.0000+
9/19/2011	0.00084%	0.0000084000	3.1549
12/5/2011	0.00000%		4.0000+
3/12/2012	0.00400%	0.0000400000	2.4771
6/11/2012	0.00000%		4.0000+

I am told MSKCC is moving to International Scale in the next few months, should be there by my next draw.  This will get me out of the business of looking at my own personal log reduction, which is good because the number basically means nothing, but since I have nothing else to measure against that is what I am using.  I am fully expecting to bounce detectable again.  My CML is like a drowning swimmer, it keeps coming up for air, but sooner or later I am hoping it gets tired and goes under for good......

[Trey]

The scale has nothing to do with sensitivity.  But they could have also changed to using different machines and/or primers.  However, most PCRs are about the same sensitivity these days; it is just that some labs truncate the results at a certain level since they know that anything beyond about -4log is pretty much noise level and prone to error.  PCRs are most accurate in the mid-ranges (roughly -1log to -3 logs).

Just a curiosity, that limit of detection of .0051 per mL does not seem right.  If it is counting BCR-ABL "transcripts" then it says it could find one transcript in a couple gallons of blood, since there are about 3 mL of blood in a sample tube.  If Phil weren't so darn contrary I might be able to lure him out by messing with the Queen's Maths here and mix mL per stoneweight and gallons per fortnight. 

[Pin]

Oh, this international scale thing is so confusing... I think this might be a measurement issue here.

Correct me if I'm wrong (Phil?), but by my calculations you're at a 3.37 log reduction (based on the 100% start value that IS uses, 0.043/100 then =LOG10(0.00043) = -3.36653].

I have a vague memory of something I read on here recently - According to a document which was linked on here and I unfortunately can't find right now (I think maybe Gerry posted it?), anything below 4 log on the IS is considered to be CMR. I wonder if that is because of the noise that Trey mentions? It is interesting though, as my doc was adamant that I have already reached PCRU (which I still disagree with), but perhaps she is referring to what the docs consider to be CMR on IS? Anyway, my point is that you are really close to that regardless.

Anyway, If anyone can find that document link, please post it - because it was really interesting reading for those of us on IS (and those of us soon to be). It was something about new guidelines for CML from Canada I think.

[GerryL]

Hi Pin,

Page 4 http://cmlsociety.or...Session-BMS.pdf

It's funny all of our PCR tests in Australia go though the same lab, yet I wasn't considered PCRU until my report stated negative under the Qualitative column. An earlier test stated I was <.002 but that still meant MMR for my doc.

Hope you're feeling a bit better.

[Pin]

Excellent, thanks Gerry - that's exactly what I was talking about!

I'm with you, I think it needs to say negative. But it is interesting to read papers like this that say anything below 4 log.

I'm not feeling the best, but that's another story and I won't hijack this thread - see if I have the energy to write one later. thanks

[LivingWellWithCML]

Ah, this is very helpful feedback - thanks everyone.  Anything below a 3.0 log reduction on IS is a good thing, but going below 4.0 log would be a great thing.  However, a detectable result (albeit, it could be noise) below 4.0 log might mean CMR, but it won't mean PCRU because the test is detecting some level of BCR-ABL, correct?  In order to qualify for stop TKI, I assume that you'd need to get fully undetectable on IS for 2+ years.

So, it looks like I'm responding well to Gleevec 400mg (and with limited side effects) ... I never really bought into the undetectable result on the 12 month test, because I continued to question the sensitivity since my 9-month result was a 2.67 log reduction.  It just didn't seem possible to go from that to 4.5 or lower in 3 months.  This seems more realistic.

Pin, I hope you feel better as well.   I go in for ankle surgery on Tuesday, so I'm out for the count on running - not looking forward to a few weeks of crutches, but it is what it is ........

[GerryL]

Hi Dan,

After a year of PCRU, I asked my doc if i could drop to 300mg - so will see in October how that is going. If I am negative at the next test I will be talking to my doctor about the possibility of getting onto the trial in Australia for discontinuation if I can get another two negatives. I don't think my doctor is going to like it much, so may find myself eventually switching doctors again. Apart from the two years of PCRU the other two things they think may be markers for discontinuation are: a quick response to the TKI and a low Sokal score.

[CDW]

Hey Dan,

remember a few months ago i had exactly the same issue when i moved from non-IS to an IS lab in the UK. thought i was BCR-ABL <0.001 and in the UK i appear to be 0.1% on the IS. so on the plus side oyur result is way better than mine (not that it's a competition of course :-))

I think it's just one of those things as you move from one system to another - and i know how dispiriting it is.

got my next 3-monthly next week where we're doing a mutation analysis just to be sure - I'll let you know.

Chris

[LivingWellWithCML]

Yup Chris - I do remember that ... wow, our journeys have interesting similarities, don't they?

Good luck with your next test and I'm betting that you'll see a great result with Tasigna ... cause you're right.  IS shows things differently, so let's watch both of our percentages continue to drop.

I hope your running is going well ... I'm going to be sidelined for a bit with ankle surgery coming up on Tuesday.  I'm not looking forward to crutches, but I am looking forward to getting my ankle fixed up.