15 replies to this topic

[JoshLee]

I had a PCR done at 8 Months and now again at 10 months. My old results were: 8 Months

% bcr/abl/G6pDH: 0.16

Equiv % K562: 0.014

At 10 Months:

% bcr/abl/G6pDH: 0.097

Equiv % K562: 0.0076

My original PCR at dx showed BCR/ABL at 1.1%....What is my log reduction?...A little confused I guess.

[PhilB]

Hi Josh,

It looks like your lab doesn't believe in the International Satnadard (IS) and is instead reporting your numbers in 2 different ways:

1. The raw numbers; and
2. Your numbers as a percentage of what the K562 cell culture would have scored on their test.

I don't know if Trey or anyone else knows how K562 compares to IS, (a quick trawl of papers made my brain ache) but it looks to me as though you started with a much lower level than average at dx ie you were picked up nice and early.  You have a further 1 log reduction on top of that since starting treatment, which is also good news.

I would ask your doctors and/or the lab what level do they consider to be equivalent to a Major Molecular Response, but I would guess that you have got one which is where you want to be

[Trey]

As Phil said you have dropped a little over 1 log from the original result [NOTE: posting clarified due to question below].  The K562 PCR % is just another confusing standardized PCR comparison value that should generally be ignored unless the percentages vary greatly from the regular percentages, which in your case they do not.

Message was edited by: Trey Fox

[JoshLee]

Trey, Do you mean the G6pDH 0.16 being my previous result that I have dropped 1 log from or my original DX? I am not on the international scale. Does this put my over all log reduction below a 2 log reduction? So the 0.097 is a 1 log drop from the 0.16? On top of a 1.1 log from DX, would this put me at CCR?

[Trey]

The 1+ log drop is from the original PCR.  As Phil suggested, you likely started at a lower level, so your log reductions may not be as impressive as others who started higher.  The 2 recent PCRs are statistically insignificant in the differences (but only a couple months apart).  I somewhat doubt that it is MMR just yet, but you need to ask your Onc to get that info for you.

[JoshLee]

Trey,

   Did you mean CCyR or MMR in your last post? I am so confused about this stuff. I had a 1.1 log reduction at 6 months. It was checked at 8 Months and it was still 1.1 and then at around 10 months and I registered a 1.3 decrease. Because I started at 1.1% BCR-ABL I don't know how much of a decrease is significant and what means that I am "stuck". When would you suggest I bring up switching medications if I need to? Would it be possible that I could be CCyR right now but because my percentage was low at dx it's not showing up as CCyR with a 2 log decrease?

[Taylor]

CCyR is also zero/negative FISH, have you reached that?  I think typically we associate CCyR with FISH and MMR and CMR with PCR.

[JoshLee]

My onc. won't really do FISH for some reason and when he does do it, he wants it done off of the bone marrow aspirate. So I will have a BMB and a FISH test done off of that in early January. Wouldn't you typically see a CCyR with a PCR that was a 2 log reduction from the original PCR? I really wish my onc. would just to fish off peripheral blood, but he thinks it's not very useful. Is it possible to have CCyR without showing a 2 log reduction on your PCR? So confused. Mainly just comforted that it didn't go up significantly, but slightly concerned it hasn't dropped very much within the past 3.5 months. Haven't had cytogenetics done since June and I won't until January 3rd. BMB's 6 months apart, which is what the guidelines state.

[PhilB]

Trey and I will never agree on this one, but to me your case is great evidence of why we DO need standardised PCR reporting as otherwise people

get stuck with numbers that they can't put in any context and although they know which way they are moving they don't know where they are.

It looks like K562 is coming in as a measurement standard because all the patient samples used to establish the International Scale no longer exist and so they were having to rely on the Australians being consistent in their procedures and then measure against them.  They therefore re-validated the international scale against K562 (which we do have plenty of) and used various different concentrations of K562 to calibrate different labs.  What is deeply unhelpful is then to report against K562 rather than to report against International Standard.  The papers I'm managing to find seem to be suggesting that 'pure' K562 is around 10% IS, but that doesn't make sense to me as K562 was a Blast phase patient so I would expect something higher.

Is there anyone on here that has had a lab test that gavce both a K562 % and an IS% so we can work out the factor?

In the absence of this information we can't say anything for certain, but:

• Your numbers have nearly halved between 8 months and 10 months.  Whilst possibly within the error limits that is still very encouraging and certainly not evidence of stalling
• A peripheral blood FISH would be nice, but hanging on for cytogenetics in Jan is absolutely fine - particularly as your PCR is still moving in the right direction
• Do you have PCR and cytogenetics numbers from your 6 month BMA?  That would help us put the numbers in context.

Bottom line is that you are almost certainly somewhere between doing nicely and doing jolly well so don't get too hung up on the numbers.

Phil?

[CallMeLucky]

Josh,

I've given up trying to figure out this log stuff.  Two reasons, one - I am not a math wiz who has a deep understanding of statistics, so I don't know enough to figure it out which means I could think I am doing good and I am not or I could think I am doing bad when I am not.  As long as my doctor keeps smiling when she sees me and tells me everything is good, I have decided to be happy with that (of course I am talking about while I am at this low level).  The second reason is that the more I learn about PCR, the more I don't trust it.  The idea that I am going to stay awake at night stressing over a hundredth of a percent on a test that can vary by how prudent the technician was in getting my sample into the machine in a timely manner, not to mention all the other stuff they have written about with PCR, it just isn't worth it.  I have resigned myself to looking at the PCR number and having an idea of what is good and what is bad.  I think I'll know when it looks bad - I'm pretty sure that would be when my doctor stops smiling.

Here's what I can tell you that may or may not help.  My lab is not International Standard (can't understand why, they are one of hte top cancer centers in the world, perhaps they think they know better or maybe it will mess with their trials, who knows).  Anyway, they use the K562 line.  When my PCR was .0081% compared to K562 I was told I was MMR.  I then went undetectable three months later and then three months after that I bumped up to .00087% compared to K562.  I just had a draw this morning for FISH/PCR and will see doctor in two weeks to discuss results.

I don't know if you can compare two patients or not, but looking at your numbers, I would say you are probably between 2 and 3 log reduction if not outright MMR.

The only think I think you should see in these numbers is that in 2 months you added another zero after the decimal point.  That is awesome and as long as you go in the right direction you should be happy.

Try not to stress over the minor details here, I don't think it is worth it, especially when you appear to be doing well.

I read a presentation given by Dr. Cortes and it had some very good quotes in it about monitoring CML

"Molecular Response is a measure of success, not a measure of failure"

"What is NOT failure to Therapy in CML -

• FISH 1-10%
• No MMR at 12 months
• PCR still positive
• Increasing transcript levels
• Chromosomal abnormalities in Ph- negative metaphases"

and one that he borrowed from someone else

"Not everything that counts can be counted, and not everything that can be counted counts." -William Bruce Cameron

(quote is attributed to Albert Einstein because he had it hanging on the wall in his office)

[Trey]

Josh,

Just guessing, you are likely CCyR but not MMR.  The FISH will confirm CCyR or not.  Either way you are making progress.

The reason I do not like IS PCR reporting is that it averages the individual into the group, sort of like Captain Picard being assimilated as a Borg.  It is individual progress as shown against the individual's previous lab tests that are most important, not averaged log reductions.  So that is why I prefer to check each PCR against the last two or so from the same lab.  The individual trend will tell the patient far more than averaged-out bovine sharts.

[JoshLee]

Thanks for all of the timely and well thought out respones, everyone. I really appreciate this.

I called Blood Center of Wisconsin, which is where my PCR test is done. I did the test last Tuesday and got the results today. I clarified something that I have been wondering about. They start everyone off against a G6pDH of 2.1% because they say that's where people are diagnosed "on average". I according to my first PCR I started out at 1.1%, but all of my tests have been compared against the 2.1% BCR/ABL G6pDh control gene. My three month PCR came back at 1.1% with a log reduction of 0 and my FISH was at 22%. At 6 months, my PCR came back with 0.15% against the G6pDH control gene and 0.013% against the K562 line and a bone marrow biopsy showed a 1.1 log reduction and a FISH test done off of BM aspirate came back at 10% (2/20 metaphases). At 8 months I switched oncologists and they reaccomplished the PCR report. It came back with a 0.16% against the G6pDH control gene and a 0.013% against the K562 cell line. At roughly 10 months I had another PCR test and this one came back with 0.097% against the G6pDH control gene and 0.0079% against the K562 cell line. If I am looking at this correctly, I am seeing this. If I had a 1.1 log reduction at 6 months and my cytogenetics were 10% and I registerd a 1.3 log reduction at 10 months, I would probably be sitting around the same number FISH wise? Maybe a little less than 10%?

[JoshLee]

I just have one final question. Is the K562 number really useless as Trey says? If it's not, why doesn't my Onc. pay more attention to it? Also, can I safely "let this go" and just assume that I am doing a little better than two months ago? I always go completely crazy around these times and just really need the assurance from anyone possible that I am not getting worse or failing Tasigna. I know that sounds needy, but this stuff is still really scary to me. I've done a great job at being rational these past few months and I have really enjoyed myself, but when these tests come back I start asking myself questions like "Is 1.1 lg to 1.3 log really an improvement? Or is just in the margin of error and I am stuck." Or, "How can they say I may be CCyR if I don't have a legit 2 log reduction?" I just get so caught up in these numbers because I am afraid. I do trust the things you all are saying and have taken the time to write and I am thankful you have taken the time. I just feel like I am moving super slow and everyone else seems to have these really dramatic drops and it honestly makes me feel bad about myself sometimes, which is so irrational, but it creeps in.

[Trey]

It is not so unusual to have a "flat spot" in the PCRs.  This is because after the TKI drug initially kills off the lower level leukemic cells, the next higher level becomes harder to eliminate.  So the progress curve flattens out for most people after a while, and can even go completely flat on occasion.

About the K562 comparison, I did not say it was "useless", but rather it "should generally be ignored unless the percentages vary greatly from the regular percentages".  So as a quality control check against your PCR numbers, it has some utility.  In your case, the numbers do not vary significantly, which is why your Onc ignores it.

If your next FISH shows CCyR at approximately 12 months, then you are right on average response.  But even slower responders have been shown to do well on TKI drugs over the longer term.  Steady wins the race.

[JoshLee]

I guess what I am asking is: Is it possible that I could be CCyR with the log reduction that I currently have? I just need something to be hopeful for I guess. Thanks, Josh

[CallMeLucky]

Trey - with regard to K569, you said "should generally be ignored unless the percentages vary greatly from the regular percentages".

My lab only does a comparison against K569.