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I think I'm a little confused about some numbers - help!

Hi,

I found out I had CML about 3 months ago. Early November. It's all been a bit of a whirlwind since then, and I'm only really starting to get my head around it now, to be honest.

One thing that I am confused about is PCR numbers and ratios. 3 months in, my BCR-ABL transcript (this is PCR, right?) is 0.76. I know that at diagnosis it was just over 3.2. When people talk about PCR numbers, I always see percents being used - does that mean mine if "76%", but if it is how could 3.2 mean 320% - is 100% not the max possible?

Anyway - I have had quite a lot of problems, presumably due to Imatinib (fairly severe muscle and bone pain) so am going to come off of it for two weeks to see if those problems subside. If so, I'm told I will probably switch to Nilotinib. If I do, I suspect I will be back here asking loads more questions of people's experience with it - I don't like the sound of two 3 hour fasts every day.

But for the moment, if someone could help clear up the PCR numbers / ratios / percentages that would be a great help and I'd really appreciate it. I did read the "PCR Results Explained" FAQ page, but I'm afraid it didn't really help me understand!

Thanks.
David.

Hi David,

So sorry to learn of your recent diagnosis. My son, Ben, was diagnosed with CML at age 10 back in 2008.

I don't really understand your post regarding PCR. There are instructions on this site about how to read the PCR. All I know is that there's a raw score and an international scale score. I think that your BCR/ABL transcript number is the amount of leukemic cells found in the drawn blood sample. The IS score is what's important - it should be moving downward. It's a slow process though. Your clinician is looking for "trends" which could take months to figure out.

About the side effects, my son had many more side effects when he started on Gleevec. He has only one real problem now: fatigue. His body adjusted to the medication and all side effects lessoned over time. All TKIs have side effects.

I wish you the very best in your CML journey.

Tracey

Hi

Sorry to hear about your diagnosis. I know it's really hard at first, but hang in there - things do get better! I've been on imatinib for over 3 years now, and at first the side effects were quite bad - bone pain and cramps were perhaps the worst - but they do get better after the first 3 or 4 months. Now, I still get occasional cramps, but no bone pain. Fatigue is ongoing, but that could be age as well, and I think you get more tired than normal, whatever drug you are on. My consultant says that, although you may get a quicker result with one of the newer TKIs, in the long term imatinib is just as good for most people. I'd much rather stay on it than have to fast for hours every day!

Whatever you decide, good luck with it.
Olivia

Hi David,

Your PCR result is ratio of the number of BCR-ABL transcripts to the number of ABL transcripts expressed as a percentage. BCR-ABL are the 'wrong' transcripts causing the the CML and ABL are the 'normal' transcripts. So 0.76% of your detected transcripts are CML ones. I think that is quite a good place to be 3 months from diagnosis. I was diagnosed 5 years ago and as far as I can remember I had something similar at that stage. I am currently 'PCR undetectable'.

I've been on Imatinib since diagnosis but I'm hoping to try Nilotinib to see if the side effects are better for me. The way I see it, the fasting required might have the useful effect of helping me lose a bit of weight!

I hope that's some help.

Best wishes

Peter

Hi Peter,

Thanks - that really helps explain it to me. It's much appreciated!

I know my doctor wanted me to be at 0.1 by 3 months, or we'd consider switching to nilotinib anyway. I've been off matinib for about 54 hours now, and feel like a new man. My legs don't hurt so much and I feel more alert. Hopefully if/when I start on nilotinib (or perhaps dasatinib if my insurance company will pay for it, which gives another option) I'll stay this way. I can only dream,

Thanks again,
David.

Hi Olivia,

Thanks ... I'm doing well, but I'm determined that since I'm only in my early thirties I'm going to give myself the very best chance to get fully better, for the long term. My doctor wants me to switch me to nilotinib anyway, given my PCR at 3 months so the side effects are just another reason to switch, I guess.

I don't love the idea of the fasting, but I'll get used to it somehow and it might force me to be healthier!!!

David.

Hi David... as other have already said- you have had an optimal response in line with the latest research: at 3 months from start of TKI therapy- PCR result shows less than 10% BCR/ABL (abnormal gene causing CML) vs ABL (or other housekeeping/normal gene)

You have a PCR result of 0.76% BCR/ABL transcript evident. This is a pretty fantastic response. However, if your side effects are causing loss of quality of life then there is a good reason to switch to either nilotinib- currently available on NHS- or dasatinib which is currently only available via application to the Cancer Drugs Fund (in England). Most people whose doctors apply for dasatinib through the CDF are given access to this TKI.
Depending on where you are treated? If in England then your area PCT will pick up the bill- and you might not need to use private health insurance to access dasatinib.
Can you let us know where you are treated?

Thanks to Chris- a member of this forum whose story is available on the vidio page- we are currently working on a patient friendly analysis of PCR tests and the meaning of results showing various bcr/abl percentages. We have to wait for further input from specialist CML clinicians before we can go ahead and publish this brochure... this seems to be taking longer than we anticipated but hopefully it will now not be too long.

Meanwhile, if you need any further clarification on PCR testing, TKIs or bcr/abl %, then please ask again.

best wishes,
sandy

Hi Sandy,

I must be getting some numbers wrong, then. My doctor said that even if I was not having side effects she would want me to switch to nilotinib. When I was diagnosed, my BRC/ABL level was 3.2 (she said this was really quite high) and now is .76, which she said was the same as 76% (I think - I still find it confusing). She wanted me below 10% by now.

I'm being treated in England, in London. My insurance will cover dasatinib but only for 12 months, so that's not ideal really. She also said that the only real chance of getting dasatinib funded would be if I had insulin dependent diabetes, or some other serious reason to not have to fast. I just don't like the idea of the 2x 3 hour fasts, but I suppose I'll get used to it.

Thanks!

Hi David,

I am confused that at diagnosis you were given the level of BCR/abl @ 3.2.

I am assuming this meant that this figure is equal to 100% PH (chromosome) positivity?

Normally you would be told that the PH chromosome is present in the 20-200 cells tested from the sample you gave...either by cytogenitics (20 cells) or FISH (200 cells).

So out of say 200 cells tested by FISH test (give or take 1 or 2) they were all positive for the PH chromosome. So from the tests done at diagnosis you would be 100% PH positive -

Once started on imatinib therapy, the first thing you want to see is a significant drop in that PH+ cell population. It is now considered that to have an 'optimal' response a drop of at least 90% Ph+ cells @ 3 months- you would then be 9.9% or less PH+.

When the % of PH+ cells is below 1.5%, it is so low that normal cytogenetic or FISH tests cannot detect their presence, your blood sample would then be tested by PCR... a highly sensitive molecular test which can detect the presence of BCR/Abl even if the PH+ cells are not detectable.

BCR/Abl is the protein that is present in Ph+CML. It is the fusion of 2 normal genes: BCR and Abl an event which is caused when chromosomes 9 and 22 swop parts each with the other.

So PCR quantifies the level of BCR/Abl fusion gene as compared to a normal gene. The comparator (or housekeeping) gene is usually Abl or BCR.

A ratio between the normal and abnormal genes is given as a percentage. It seems from what you are saying, you have been told that the presence of BCR/Abl is now at .76 which I assume is equal to you being 76% Ph+ ? So you have had a cytogenetic response of 24%.

This is why your doctor wants you to switch to nilotinib- the next available TKI available through the NHS.
Although the Cancer Drugs Fund in London, lists dasatinib as available, it seems that you need to have tried nilotinib first and either to be resistant or intolerant.

see link below and scroll down the list to dasatinib:
http://www.london.nhs.uk/webfiles/Cancer%20drugs%20fund/2.%20London_Canc...

This is why your doctor is saying that you would need to show other clinical needs to get from imatinib direct to dasatinib.

So yes I agree... you will have to get used to the 2 x 3 hour fast every day. But others have done it and have seen a vast improvement in molecular response- which is what you want to see after all.

From your current 76% Ph+ivitiy, you doctor (rightly) wants to see a major cytogenetic response (MCyR)- to less than 10% (Ph+ cells)
MCyR- < 10%
then
Complete Cytogenetic Response (CCyR)
CCyR- 1.5%
and then on to a molecular response- preferably below MR3- 0.1%

I hope I haven't confused the issue further. It took be a while to figure it out ;o)

Sandy

You haven't confused it at all! I'm still not fully there on PCRs, cytogenetic and molecular responses - but firmly on the road to understanding!

The 3.2 number at diagnosis wasn't told to me then, in fact I only saw it a couple of weeks ao. It was from a PCR test that was done on a blood sample from diagnosis, but that's not what was used to make the diagnosis itself - if that makes sense.

My diagnosis was confirmed from a FISH test. In my diagnosis letter is says "confirmed by FISH"l so I can not assume that 3.2 PCR number was done after the fact.

It appears that I am left with too many options!

1) take nilotinib. The point of all of this is just to get better, and I know that it sounds childish to moan about the fasting - so it's not really a bad outcome
2) take dasatinib for 12 months because my private insurance will cover for that period. What to do afterwards though? I could almost certainly get treated in Ireland after 12 months (where I am originally from), and I believe dasatinib is approved there

Moving treatment to a different country from where i spend most of my time hardly seems like a good idea, so I reckon maybe I should just stop moaning and start concentrating on clinical effectiveness not my stomach!!! It's just frustrating that a medicine that would help with my quality of life is out there, but not available to me. I'm only 33 so have a long time left to take this medicine and in my "old" life I'd take clients out at various times of day and night many days of the week, it was easy to be flexible but I suppose it's not the worst price to pay. It just feels like a big intrusion to my life, whereas the other drug wouldn't be. Oh well. I dasatinib was never invented, I wouldn't be making a single complaint!

Thanks for all the help - I really, really appreciate it. It's been invaluable since day 1.

David.

Hi David I have found life on Nilotinib rather better than on Glivec! Good results in the lower 0.0s for a while now.

One option for taking the tabs is to set the alarm for an early pill say 5am, then go back to sleep till normal, but DO sleep more upright as the tabs can cause damage to piping on the way down !!! Drink a good glass full of water when you take them. Then take the second dose at 5pm that way you can have a cuppa and snack at 3, and supper at 6ish. Other way some people do it is to take tabs at 11 and 11. These seem to be the most popular timings I've come across.

Good luck
Pennie

Thanks Pennie - the middle of the night idea is something I think I will try. If I can get used to it, I think it will work well with my 'previous' lifestyle. I know I'm being too precious about the whole fasting thing, but I am sure I'll get used to it eventually. The main thing is health.

David.