5 replies to this topic

[Tedsey]

I don't know if I have false memory syndrome, but I remember hearing that if your reach CCyR, there would be a 2 log reduction in your PCR.  Since it doesn't look like I had a 2 log reduction yet, I assume this is not true.  I am just asking because I will be relying on PCRs to shed light on the cytogenics until I have my next BMB in May. 

Although, I was first diagnosed just over a year ago, I didn't have a reliable PCR until last May.

5/10     13.739%  (had another one done a few days later that read 9.378---That seems like a big flux; so what looks like a log reduction to me could not be one)

8/10      4.921%  (this number is where my onc thought I wasn't making good progress on Gleevec and switched me to Sprycel)

12/10    1.334%  (on Sprycel 3 months--doesn't look like miracle progress, but it is lower)

From my limited understanding of log reductions, although I see no zeros, the difference between 13.739 and 1.334 is greater than 10.  So, I think this would be 1 log down.  Does this look like an average response or am I still considered a slug?

Teds

P.S. LabCorp does the PCR.  I am still unsure what the lab control is.  So I don't know the disease burden, like, if these numbers are sky-high, low, or just average.  I just got my molecular report back and it said this time that in 3% of CML patients, the gene fusion occurs without cytogenic evidence of rearrangement (guess that would be PH- CML).

Here are my questions to make it easier:

1) Did I have a log reduction?

2) What is the common margin or error for PCR testing?  Could you provide a sample?

3) Do you need to see zeros for a log reduction (if answer to 1 is yes, then I get it).

4) Is my disease burdon still high?

5) Am I making average progress with the PCR values?

6) Is PH- CML better than PH+ CML?

7) Does having PH- CML mean there is something else causing the BCR-ABL fusion protein (or is the mutation probably there, but in too small to be detected)?

8) If you are considered in a CCyR, then do you have PH- CML?

[PhilB]

Hi Tedsey,

I'm not sure whether Labcorp are on the International Scale yet, so tricky to say anything absolute, but:

1) Did I have a log reduction?
You have a 1 log (ie ten-fold) reduction between 5/10 and 12/10 based on those numbers.  It's reasonable to assume you also had some further reduction between starting treatment and your 5/10 test so you're probably well over 1 log reduction overall.  If it is on IS then you are very close to 1% which is what the lab would deem a 2 log reduction from standard baseline.

A 2 log reduction is often taken as 'roughly equivalent to' CCyR, but there can be quite a bit of variation in that.  The true definiton of CCyR is 'we looked at 20 cells and didn't find a baddy'

2) What is the common margin or error for PCR testing?  Could you provide a sample?

The lower the levels the higher the error.  The only way to reliably show this is by getting the same sample tested multiple times.  Studies I've seen where that was done frequently show differences of around half a log when you get below the MMR level

3) Do you need to see zeros for a log reduction (if answer to 1 is yes, then I get it).

Nope.  You just need to see the decimal point moving to the left.  If you were 87% by PCR at dx then 1 log reduction would be 8.7%, 2 log would be 0.87%.  On the international scale it goes 100% = baseline, 10% = 1 log, 1% = 2 log, etc

4) Is my disease burdon still high?

You probably still have millions of Ph+ cells, but no your disease burden is no longer high as the vast majority of your cells are now normal.

5) Am I making average progress with the PCR values?

The target for 12 months is CCyR and you have met that.  There are no prizes for getting there faster or slower, but your PCRs are dropping nicely.

6) Is PH- CML better than PH+ CML?

You need Trey for Ph- CML as it's a whole different kettle of fish.  Given that we have all these nice drugs for Ph+ CML you'd definitely rather have Ph+

7) Does having PH- CML mean there is something else causing the BCR-ABL fusion protein (or is the mutation probably there, but in too small to be detected)?

Trey again

8) If you are considered in a CCyR, then do you have PH- CML?

No.  You have Ph+ CML which is responding well.

[Tedsey]

Thanks Phil.  I often need lots of reassurance.  It eases my soul to understand as much as I can and get validation for what I think I already comprehend.

All the best,

Teds

[Trey]

A PCR 2 log reduction and CCyR are very roughly equivalent.  But if I had a FISH and a PCR side by side I would go with the FISH results.  A PCR has a margin of error of 1/2 log, but if the sample is degraded significantly (PCR test is not done until over 36 hours after blood draw) then the error rate is even higher.  This is why we should never have a PCR blood draw on Friday, or even Thursday.  I recommend Monday - Wednesday and before Noon if possible to line up with FedEx schedules.

"Philadelphia Chromosome negative CML" (Ph- CML) is a type of leukemia where there is no detectable Philadelphia Chromosome, but there is full-blown leukemia that includes BCR-ABL.  But that is probably due to rare and very different breakpoints that PCR and FISH cannot recognize.  The PCR only looks for b2a2, b3a2, and sometimes e1a2 if specified, but there are many other possible breakpoints.  There is debate whether Ph- CML is even a type of CML, or something completely different.  This is NOT an issue for you.

Given your overall issues you should be encouraged about your progress.

[CallMeLucky]

Based on my numbers, it appears the estimate is very rough

1st PCR 1.2%, FISH 498/500, BMB 20/20

2nd PCR .25% (approx 1 log red), FISH 25/500, no BMB

3rd PCR .367%, FISH 3/500, BMB 0/200

So for all practical purposes this can be interpreted as having a CCyR correlated to a 1 log reduction in PCR

In my case appears PCRs may have a bit of variance

[jwbwater]

The lab that did your PCRs should report a median PCR for previously untreated patients.  When I was getting mine done by a Sonora Quest lab their median was about 3.5 so even though you've only had a 1 log reduction from your first PCR you are probably about 2 logs below the median for newly diagnosed patients.