Anyone have a PCR result above 100% at diagnosis?

Yes, mine was 321% at diagnosis.

The IRIS trial was the first formal demonstration of the dramatic superiority of imatinib over interferon based regimens. RQ-PCR analysis for the trial was centralised in three centres – Adelaide, London and Seattle – that used different laboratory procedures. It was observed that reproducible differences in median BCR-ABL values were being measured between the three centres at specific timepoints which prompted the need for an urgent alignment of their respective results. In the absence of any independent reference materials, the decision was made that each centre would measure the level of disease in a common set of 30 pretreatment samples, and that patient results would be normalised to this standardised baseline (100%). Reanalysis of the data showed improved comparability of results between the three laboratories and the standardised baseline was used to normalise all IRIS RQ-PCR results. Thus, major molecular response (MMR) is defined as a three log reduction from the IRIS standardised baseline and not a three log reduction from pretreatment material for each case. 

So because of that, 100% isn't a theoretical ceiling at all - it's just the average PCR result you'd expect of a newly diagnosed patient. Some will be higher, some lower. But we all then use 100% as a baseline for comparison when we talk about log drops.

Perhaps someone will know the detail better than me.

David.

At diagnosis - the only measure that means anything is FISH (Fluorescence in situ hybridization). PCR is meanginless at diagnosis.

FISH is a process where a sample of blood cells (typically 200) are 'dyed' with a fluorescing compound that binds to bcr-abl gene specifically. Then a technician looks under the microscope and counts number of cells out of 200 which fluoresce. The ratio of fluorescing cells to non-fluorescing cells is expressed as a percentage and can never exceed 100% by definition. Most of us were diagnosed at 100% bcr-abl.

Only when FISH drops to less than 1% does PCR become more meaningful and useful.

Think about this: When FISH drops to zero, under the microscope, CML is not observed, there are ZERO cells showing bcr-abl. In other words, there are very very few CML cells. This is why we feel terrific again after just a short TKI treatment. The bulk of CML cells have been killed off. There are so few CML cells left, we can't even see them.

PCR at this point in time is around 1% - and is strictly a molecular measure determined in the way described earlier in this thread. PCR is measuring for the bcr-abl protein - not the oncogene which transcribes the protein. The amplification process used in the lab to get bcr-abl gene to produce enough bcr-abl protein so it can be measured is not exact and has so many factors which affect the rate of amplification - hence the various PCR numbers across labs (even despite so-called standardization). However, for our purposes, once FISH falls below 1%, PCR serves a very important role as canary in the mineshaft. Any bcr-abl protein made above what is already a miniscule amount (see FISH above), gets detected. It's this detection we really want to track and know about.

PCR < 0.1% is a very very low level of residual disease. CML would have to grow an order of magnitude above this level just to have maybe one cell out of 200 show up under the microscope. That's how low 0.1% is when using PCR.

Thanks for the explanation Scuba. I’ve been paranoid since the beginning when I heard that my first PCR was 13% after seeing everyone’s was above 50%. I thought something odd was going on and that maybe they’ve screwed something up. This test was performed twice a year ago and they also tested for p190 which i don’t have and have the regular p210. Hoping I’ll reach MMR I was 0.3% at my 12 month. Consultant not concerned at all but I am if I am honest considering I am on a 2nd Generation drug. Hope the drop continues and I’ve not plateaued already. Time will tell at 18months!

Yes, my PCR score was above 100%.

PCR - p210 transcript 118.7% IS

FISH - 93%

cytogenetics - t(9;22) translocation in all 20 of the metaphases examined

WBC - 65.5

I received my latest PCR score last week and it was .007% IS.  I've been alternating 20mg Sprycel with imatinib for the last year or so.  I think I'll take 250mg imatinib for the next month and then switch back to 20mg Sprycel for a month.  I've included my CML history below.

My diagnosis started after I gave a routine blood donation to the Red Cross. The hematologist with the Red Cross notified me that my WBC was high and recommended I follow up with my primary doctor, which I did. He ordered some blood tests and immediately referred me to an oncologist. 09/2012 p210 transcript 118.7% IS @ Dx, t(9;22) translocation in all 20 of the metaphases examined, FISH - 93%, WBC 65.5, began Gleevec 400mg/day 12/2012 003.59% & bone marrow biopsy - no residual myeloproliferative features but detected 1/20 metaphases containing the Philadelphia chromosome, FISH - 5.5% 2013 000.914%, 000.434%, 000.412% 10/2013 000.360% & bone marrow biopsy - normal male karyotype with no evidence of a clonal cytogenetic abnormality 2014 000.174%, 000.088%, 000.064% 2015 000.049%, decrease to Gleevec 200mg/day, 000.035%, 000.061%, 000.028% 2016 000.041%, 000.039%, 000.025% 2017 000.029%, 000.039%, switched to generic imatinib 200mg/day, 000.070%, 000.088% 2018 000.233%! Tried switching to dasatinib 100mg/day - I want zero #4 back! Dasatinib at 100 and then 50 mg/day did not agree with me so I went back to generic imatinib 300mg/day. 000.013% The dasatinib did seem to be effective. It was probably just too high of a dose for me. Went back to a lowered dose of dasatinib, hopefully that will keep the side effects away and still be effective. 000.007% Dasatinib at 25 mg/day seems to working! 20mg/day Sprycel or 200mg/day imatinib 000.006% 11/19-21 three day fast 2019 000.007%, 000.007%