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More pcr confusion...

Hello everyone

I'd be really grateful if anybody could shed some light on this latest result.

My husband had an appointment with his specialist nurse this morning for his blood tests and to get the results from last time. She wasn't there as she's ill, so he was actually able to see his consultant instead, which is great.

Anyway, at his two previous appointments the nurse said he was down to zero, the disease was undetectable and in effect he was disease-free. I was present at one of them and questioned her about the zeros (after reading posts on here of course!) although she said, 'it's just zero.' We were absolutely delighted, as you can imagine.

Today, however, the consultant told him he was at 4.5% from a starting figure of 124 (when diagnosed in December 2010), and which was down from 6.2% last time. To give you a bit of recent background, in October the nurse had told us he was at 6.7% pcr after the previous test which was 4% (Sandy kindly explained at the time that the 6.7% pcr result was better than the 4% FISH test).

You may be as confused as I am by now, but how could the specialist nurse have said he was at zero when it seems he wasn't? The consultant was pleased and said it's all going in the right direction and that he expects him to get to zero in the next 12 months, but I just feel quite uneasy about the whole thing. Am I missing something (again)?

Thank you so much for your help.x

I am not surprised your are confused! First- you need to see the consultant in NOT the nurse in future. She obviously needs to do a bit more study regarding pcr, cytogenetices etc.... and what zero and undetectable means! I am amazed at the previous interpretation of your husbands results.

The good news is that you now have some clarity...

but just for my own understanding and to make sure I have not forgotten or misunderstood anything...... can you answer the following questions.

1. Are the following figures correct according to the consultant as of today?
(best discount the previous results given by the nurse).

baseline figure at diagnosis Dec. 2010 was 124% bcr/abl (or 100% Ph+ cells)

achieved a Major Cytogenetic Response: 6.2% bcr/abl in October 2011 (at 10 months)

todays pcr is 4.5% bcr/abl (16 months)

You say the consultant is pleased and expects a CCyR within the next 12 months?

Your husband is being treated with 400mg imatinib?

The timeline above is correct? i.e diagnosed in Dec 2010 in chronic phase?

Sandy

Hi Sandy
You do make me feel so much better, thank you.
Yes, all those statements are all true.
I don't want to criticise the nurse as she has been so incredibly supportive and helpful (to both of us) from day one, and has really put herself out to ease the cml journey, if you know what I mean? We were feeling so positive, but that knot is back in my stomach now.x

Morning,

Sorry to hear the confusion re the results so far, it is as I have found before very frustrating. I would look very much at the fact still falling.

A question please, why is a higher PCR better than a lower FISH test as reffered to in the posting above " To give you a bit of recent background, in October the nurse had told us he was at 6.7% pcr after the previous test which was 4% (Sandy kindly explained at the time that the 6.7% pcr result was better than the 4% FISH test " ?

Thanks Nigel

Hi Nigel,

FISH tests only up to 200 cells - it is thought to have a false/positive result- so in my view it is pretty inaccurate compared to RT-QPCR- but FISH is fine for the initial testing when your % of Ph+ cells are very high-
i.e at diagnosis when most people can be said to be around 100%.

FISH identifies Ph+ cells by a kind of florescence staining technique using dna probes.
If say 4% of 200 cells are Ph+ that is equivalent to 8 Ph+cells
Therefore:
if you have millions/trillions of cells in your blood and in every batch of up to 200 cells in any one sample, 4% (8) are Ph+, it follows that in every batch of 200 cells there would be 8 Ph+ cells and this would be replicated over and over again in every batch of 200 cells you could possibly test.
so potentially this 4% might mean there is quite a large population of cells that are Ph+

However, by Q-PCR testing:
If you are testing a sample of say 1,000,000 cells, this is a much bigger proportion of your white cells.

So although 6.7% is larger than 4%- the pool you are testing by PCR is enormous compared to FISH

PCR is therefore a much more reliable and accurate picture of the actual situation in the marrow/blood and the level of disease that is left.

I said that 6.7% by pcr would be a better result than 4% by FISH, because according to my own (lay) understanding of all this,
6 .7%- is equal to a drop of around 93%.

Even so- we know that even when you get down to 0% there are still a lot of Ph+ cells left- ... that is why we are told to aim for MMR - at least 3 log reduction or 0.1% on the international scale (IS)-

We should expect to reach MMR or 0.1% by 12- 18 months from start of therapy.
However there has been recent research from Hammersmith (Marin et al) that shows an optimal response is <10% or a 1 log reduction within 3 months from start of therapy.
But this is optimal and it must be said that many people have responded within a much longer timeline- and have gone on to MMR and even lower.

See below for % responses on the International scale (IS) and the same results explained as 'log reductions'

100% Ph+ at diagnosis

IS Log reduction
50% = 0.5 log
10% = 1 log
5% = 1.5 log
1% = 2 log
0.5% = 2.5 log
0.1% = 3 logs ___________________________major molecular response MMR________________________________

0.05% = 3.5 log
0.01% = 4 log

0.005% = 4.5 log_________________below this level is a complete molecular response CMR
0.001% = 5 log or as some people say PCRu (undetectable disease)

Best... Sandy