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Rising PCR and Ph chromosome, worried

Hi,
I am quite confused and worried by my recent 12 month biopsy and PCR results.
I am taking part in a trial and was moved from Glivec to Nilotinib at the 6 month mark.
I've been feeling great on Nilotinib and my PCR at 9 months was 0.32 which I was v pleased with.
Unfortunately I have had raised liver enzymes and had to take 2 months off the meds for them to return to normal (am back on them now). At my 12 month PCR in Nov my BCR-ABL had risen to 0.48. I was not too concerned as that was only a slight rise but I have just had the results of the biopsy which worries me. 13 cells in 35 had the ph chromosome (compared to 1 in 30 at the 6 month biopsy.)
I am confused as I thought the PCR and biopsy results would correlate in some way and my PCR is fairly low.
So at the 12 month mark I haven't achieved a complete cytogenetic response or a major molecular response and this worries me. I am getting worked up and feel that my CML might be 'aggressive'.
Does anybody who has a better understanding of the disease have any thoughts?
Thanks
Kate

Hi Kate,

It might be that your biopsy hit a 'pocket' of ph+ cells - this happened to me-given that only 35 cells were tested. so this might be an explanation for the disparity between the pcr and the cytogenetics tests. Your pcr shows a major molecular response - so try not to worry too much. Ask you consultant for an explanation about why the results do not  match. If the biopsy was done by FISH testing there is quite a larger false/positive possible with that method of testing- but do consider asking for some feedback so you can stop worrying needlessly. 

Best... Sandy

 

Hi Sandy,
Thanks so much for your response it has put my mind at ease. I will
ask for feedback too. I have a question about molecular response. Is a Major Molecular response a 3 log reduction? If so mine would need to be 0.052. I've also heard from my doctors that it can be classed as 0.1. My worry is that I haven't quite got there yet and I read that the 12 month results are important.
Thanks
Best wishes
Kate

Hi Sandy,
Thanks so much for your response it has put my mind at ease. I will
ask for feedback too. I have a question about molecular response. Is a Major Molecular response a 3 log reduction? If so mine would need to be 0.052. I've also heard from my doctors that it can be classed as 0.1. My worry is that I haven't quite got there yet and I read that the 12 month results are important.
Thanks
Best wishes
Kate

Hi Kate,

MMR is defined as either a BCR/Abl ratio of less than 0.10% or a 3 log reduction from the mean PH+ level of 30 patients enrolled in the IRIS trial- this was then used as the baseline. 

CMR (complete molecular response) is defined as undetectable levels of BCR/Abl.... however that depends on how sensitive any given PCR test is. For example some labs in the US would give a reading of 0.000 (undetectable) whilst others in Europe (eg. UK Hammersmith) would show positive for BCR/Abl from the very same sample.

Generally it is agreed that 4.5-5 log reduction constitutes CMR- but it is known that there is still residual disease blow this.

 

Hammersmith have recently introduced a much more sensitive PCR test- so CML patients who were previously showing CMR 0.000...% are now showing 0.00001%- this does not mean they are relapsing. It means that the test is more sensitive.

 

12 months is a general goal- so is what you might determine as an optimal response... but this does not mean that everyone must reach the same levels at the very same moment. We are all individuals and will respond accordingly with some slower than others. The fact that you have had problems with nilotinib affecting your liver enzymes means you have had to take time out of treatment so this will affect the time you achieve the desired level - it is not an exact science ;o)

 

Best wishes,

Sandy