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Just when I thought I understood PCRs!

I'm confused again! Still, I think it's a good result to be confused about so I'm not complaining.

After a bit of a struggle with imatinib, a switch to dasatinib and a recent fundoplication to try to get the PCR lower, my latest results are in (bloods from a month post-op).

My hospital result came in at 1.2%. The Hammersmith result (from the same bloods) came in at 0.4%.

One would indicate MMR, one wouldn't. They out by quite a bit in comparison to each other.

Here's where I get confused. My oncologist says that the Hammersmith result is correct, and that the other result needs a scaling factor applied (nb: NOT a iris conversion factor). The reason for this, I was told, was that because I was diagnosed with a BCR-Abl of over 300%, to get to a comparable number you need to scale the result down because the PCR that they run is relative to that original result. I'm confused, because I thought the IRIS numbers were already calibrated.

Anyway, if you scale 1.2% by .3x (100% / 300%) you also get to 0.4%.

Don't get me wrong, I am delighted to get to 0.4%, I'm just a little confused as to how we got there!! I guess the Hammersmith lab is the one to trust at the end of the day though.

Has anyone else had experience of interpreting results which originally were above 100% on the IRIS scale?

Anyway. I'm off for a glass of bubbly. Feel very happy to have got to this point so quick after the fundoplication - maybe it wasn't the reason for the recent drop, but it can't have hurt.

Thanks,
David.

Hi David,

yes it is confusing, so much so that I asked my doctor and she agrees that maybe 'someone' is confusing logs with the international scale. Great that you have a result of 0.4% so quickly. It's good that your samples are also sent to HH lab.

Sandy

That "someone" is almost certainly me :-)

Thanks for your help on this. Much appreciated.

Hi David, not just you- I asked my doctor about how it was possible to be more than 100% positive at diagnosis and she explained it like this:

"With respect to the 300% this is not uncommon. The problem is that the PCR test is designed to find a rare event so it is at its most accurate when the event, i.e. the leukaemic cell, is rare."

Unlikely at diagnosis!

"When all the cells (in a sample)are leukaemic it swamps the test so you get all sorts of bizarre results – from 60-300%. That’s why good labs never talk about log reduction from the individual patient’s baseline."

I now understand how we become confused! Learning about molecular biology and PCR testing is an ongoing ambition, and quite a hard slog!

Hope this is helpful,

Sandy

Six years in and i still feel that i struggle to understand all the types of results and the fact that you have to be able to adjust them for the International Scale. Still fantastic results for you David - congrats.

K

Congrats for the good result, david!! I got confused with my results too! i saw 25% ratio first and thought it was bad, then i looke ate "international scale convertion" and it was 14.4%. When you say 300%, i think you're talking about ratio (this is not the final result). My ratio at dx was bigger then yours. it was 361%.

The problem is that at diagnosis it is very likely that every cell in the sample will be positive. At this stage q-PCR testing is unreliable, apart from as a qualitative(rather than quantitative)test, to confirm (or deny) that you definitely have PH+ CML. That is why in the initial stages, cytogenetics/FISH tests are used, at least until the PH+ cell population comes down to lower levels. At these low levels, particularly below 1% BCR-ABL, q-PCR is highly sensitive and very accurate.

Sandy