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A bit confused with recent FISH result

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Diagnosed latter part of April 2018.   Started Sprycel 100mg May 12, 2018.

FISH at diagnosis 87.67   qPRC at diagnosis 116.47%

Had my three month testing done on August 6.   I was quite happy to get my qPRC results a couple of days later at 5%.

I had forgotten that they also ordered a FISH.   I received an email today telling me that new information was posted to my online chart.  When I pulled that up my FISH result was there at 13.5%.   My understanding is that greater than 10% FISH at 3 months is suboptimal.  

I have a question into my onc, but I'm curious if others have had conflicting results such as this.  I've tried to find some information via Google, but haven't had much luck.

Thanks for any info,

Mark

You’re doing fine your latest PCR is <10% at 5%. All these numbers are confusing I am still learning myself! Have my first 3 month PCR next Friday so I understand the anxiety. It’s the PCR that counts and at 6 months they expect you to be around 1.0% and at 12 months 0.1% known as MMR or a log reduction.

You are doing really well you should be celebrating

All the best

Alex

MJP -

FISH is the most important measure and prognosticator of success in CML treatment. FISH counts actual CML cells under the microscope and is expressed as a percentage of normal cells. At diagnosis most of us have 100% FISH - meaning that every cell looked at and counted under the microscope shows the gene for bcr-abl (CML). Over time this percentage goes down until finally no CML cells are observed (FISH = zero). That is your immediate goal. PCR means nothing until your FISH goes to zero. Zero FiSH = complete cytogenetic remission and the single most important milestone for progression free survival. As long as your FISH results are trending downward at each test, you are doing fine. At your rate (it's not linear) you should easily get there within a year to 18 months. I suspect you will get there very quickly.

Once FISH = zero, you still have CML, it's just so depleted that no cells are observed under the microscope, but cells are still there. That is where PCR comes in. PCR measures the proteins produced by CML cells (specifically the bcr-abl protein). In order to get a measure of the small amount of protein, lab technicians have to actually "amplify" the signal through a chain reaction process and then compare against a standard. PCR is not that accurate because of this process, but it is sensitive - so a little bit of bcr-abl protein can get "detected". It is a molecular measure and is used as the proverbial canary in the mine-shaft. As long as PCR is low (below 0.1%), CML tends to be stable and very well controlled by that point. When PCR falls below 0.01%, the results become meaningless (beyond the limits of the technology) and is indistinguishable from "undetected" in practical use.

There is a rough correlation between FISH and PCR.  Above FISH = zero, PCR can range anywhere from a few percent to hundreds of percent. It's not very useful when FISH is greater than zero. Once FISH is zero, PCR tends to be around 1% and PCR testing becomes the only way CML progress is tracked.

FISH is a cell counting test expressed as a percentage. PCR is a molecular test expressed as a percentage of bcr-abl protein against a normalized control gene (which is why you can have over 100% PCR. Mine was 155% at diagnosis.)

Thank you.  

Thank you, Scuba, for your explanation provided above. I found this using the search tool. Incidentally, the search tool provided on this site is excellent.

I have re-read your posting about 10 times over and it makes very good sense now that I have my 12-week results and I am starting to learn a lot more.

My haematologist explained to me that it used to be considered that anyone with a Ph positive test result would be diagnosed as having CML, however, it is recently been recognised that many people off-the-street can have Ph positive results without having CML. It appears that people with CML somehow have the inability to correct the genetic irregularity that has occurred.

Anyway, the use of terms can be confusing. In Birmingham, the FISH result is referred to as the "Ph+" result and the PCR result is referred to as the "BCR-ABL" result. This corresponds with the European LeukaemiaNet explanatory slide to which my haematologist refers.

So the 12-week optimal response for Ph positive is less than 35%, and the optimal response for BCR-ABL is less than 10%.

My result was Ph positive is17% and BCR-ABL is 15%. On the face of it, it would seem that I have failed with the BCR-ABL which should be 10%. But my haematologist tells me that Ph positive (FISH) trumps BCR-ABL at 12-weeks.

This is all consistent with your posting, Scuba, and I thank you again for taking the time out to explain these matters in simple terms. This is very reassuring.

 

The number 9 and number 22 chromosome are packed next to each other very tightly right at the bcr and abl breakpoints. Translocating these genes is very easy and most certainly happens all of the time in the general population. Having CML cells is probably a normal occurrence. And this type of translocation probably occurs at many other sites along chromosomes. Many are benign and self-destruct and some are responsible for other cancers along with CML.

What is different for us CML patients is that we lost the ability somehow to 'check' CML cells from proliferating. This is key.

ALL cancer is a failure of our immune system. We generate cancer cells all of the time. Our immune system is able to recognize them and kill them. Also - the cancer cells themselves have built-in DNA coding to cause them to self-destruct as well. What causes cancer to get out of hand is a combination of bad luck, environment and genetics.

One cancer cell is not enough to initiate cancer. The cell can not put out enough "do not attack me" protein to turn off T-cells which will attack. Our normal cells pump out "do not attack" proteins which lead T-cells to stand down. Autoimmune disease such as multiple sclerosis results when this "stand down" mechanism becomes faulty. We have billions of normal cells so they are effective at T-cell attack control. But cancer cells starting one at a time (i.e. normal population) don't have the population to pump out enough "do not attack" proteins. This is why CML is actually quite rare.

So how do we get CML?

Two ways (this is my personal opinion based on study):

1. Sudden, very large population creations as when radiation hits us (i.e. CT-scan) in our large bones (hip/pelvis) to suddenly cause the 9;22 translocation in our blood stem cells and voila - instant CML population which creates "do not attack" protein in large amounts and causes the T-cell response to be muted and ultimately ineffective. Disease results.

2. Niche protection in the bone marrow. A few cells get started and are able to evade T-celll attack because the T-cells never get to them. The population of CML stem cells keeps growing and growing and finally when T-cells see them - they are large enough in number to tell the T-cells - "leave us alone".

This is why immune health is so important. (and why I take vitamin D3 to help my immune system along with K2).

TKI's, in my mind, are nothing more than population control (like killing fleas). By hitting CML's cell population - for some of us, the population is reduced so much so that T-cell attack can become effective again and functional cure is achieved. Do we eliminate CML? Probably never. 9;22 translocation is always going to happen - but with immune control restored - it never gets re-established. TKI's don't cure - but our bodies may be able to restore "cure".

Biology is not all or nothing. So many degrees of function for all of us. Curing cancer lies in finding a way to activate our immune system to kill the cells naturally. Only then is cancer "cured".