11 replies to this topic

[Barb@Anderson]

My Oncologist told me last week that my ABL-BCR went from .3 in July to 5.0 in November and today he called and said bloodwork last week showed it was still climbing and suggested a change in dosage of Gleevec before making a change to another med. When first dx I was taking 400 MG and it was dropping to much so my other onc dropped it to 200 a day.  Now this dr wants me to take 400 Mon, Wed, and Fri and the other days take 200 mg.  Can somone explain to me what the numbers mean.  I am not up on all this.  I've tried to read all about ABL-BRC but it seems all Greek to me.  I understand when I get my bloodwork and the WBC, RBC and all those numbers.cause it will show what the baseline high and low should be.  I just don't understand the ABL-BCR thing.  Don't want to seem like a dummy but I know when my body tells me something is wrong and the med must not be working as well as anymore.

[CallMeLucky]

BCR-ABL is the gene that causes the Philadelphia Chromosome, which is what causes CML.  The BCR-ABL tests tells if the drugs are keeping the disease under control.  In your case they are not because you are not taking enough of the drug.  200mg of Gleevec is not an effective dose.  I would question how many patients your doctor has on Gleevec and how many he has done this alternating dosage with.  My guess is very few and he is experimenting.  You need to be on a drug/dosage that works.  What you are doing now is not working and not very wise to "experiment".  There are a number of CML drugs that are very effective.  Gleevec is a good drug but if you can't tolerate it then try something else.  I would get another opinion from a CML specialist before taking chances with dosage any longer  You need to get the disease under control and stable.

Best of luck.

[Susan61]

Hi Barb:  What does your doctor consider to be low.  I have been on Gleevec for a very  long time.  My WBC runs constantly around 3.2. My platelets are around 117.  I would have to look at my last blood work.  I have remained stable at that count for a very long time.  Lucky is right, you cannot play around with dosing.  Go see another doctor who treats CML on a regular basis, and just take copies of your tests to see what he thinks. Its your body and your life, and you have the right to get another opinion before switching drugs.  If you were to look at my blood work sheet, you would see all abnormal counts in the low range.  I have been PCRU though for 10 years.

Once you get stable, you will do okay.

Susan

[TeddyB]

Barb: You should get a second opinion from a CML expert.

[Trey]

Your Onc is talking about the PCR test, and should call it that.  Your  200mg Gleevec dosage is below what is recommended, but is temporarily reduced due to your side effects.  You need to take more drug, and the Onc is trying to work you back up to 400mg daily, which is where you should be.  The 200mg daily is obviously not enough dosage for you.  You simply need to work back to taking higher dosage Gleevec or change drugs to one that you may tolerate better.

[CallMeLucky]

To clarify one thing, while trying 200mg to see if it reduces side effects and still keeps disease under control is certainly something doctors do, what seemed "experimental" was the whole Mon, Wed, Fri thing.

[Barb@Anderson]

thanks Trey, could you explain the PCR test.  What does it check?  I've read others talking about all these test and numbers on here and I guess I'm sorta hard to get things into my head but I just don't understand it all.

My other Ocologist that had to retire last Oct explained things more than the one I have now.  Would change but the other cancer clinic is so far away from my home and I can't afford since gas is so high as well as copays and extra for bloodwork.  I don't mean to sound pesimistic but I am so tired of all this going to dr and tired of just bing tired. 

[mariebow]

Barb, I feel you.

[Barb@Anderson]

Yes mariebow, I think if all of those with CML were honest they would say the same.  My family and friends say I should be thankful to have been dx early on but they don't have to think about it day and night.  Stress is on high level right now not knowing if my CML is progressing to a blast phase or just need to try a different med.  Sorry to vent like this but you guys are the only ones that I can talk to that might understand.  thanks for being a sounding board.  

[jjg]

Hey Barb, I'll have a go at an explanation - anybody feel free to correct!

As Lucky said BCR-ABL is the messed up gene that causes CML. A PCR is a technique that allows us to measure the amount of the BCR-ABL gene. There are other ways to measure the amount of it but the PCR allows them to measure very small amounts. The most simple way to measure the number of bad cells is to use a fluorescent marker that only attaches to the bad cells and then count the number of cells that glow in the dark. But this only works when the percentage of bad cells is quite high, typically greater than 1%. The thing about blood cells is that there are a lot of them - a normal WBC is 3.5-10.5 billion cells per liter and an average adult has 5 liters of blood. Even one cell in our blood with the BCR-ABL genetic material means that we have CML ie. 1 in billions, so clearly we can't just count cells to work out what is going on once the level of leukemic burden gets lowish.

The PCR test is a way of amplifying the amount of genetic material i.e. the BCR-ABL in a blood or marrow sample so that we can count it. Don't ask me for the specifics, I'm an engineer :-), although I do occasionally work with people who research platelets and WBC and they assure me that the PCR test is not hard at all. It's a little like taking a picture of something and then seeing something really small in the top LH corner that you want to measure the size of. So you zoom in and the picture becomes all pixelated but at least you can see how many pixels across the thing of interest is and if you know the pixel size you get a rough estimate of the size of the object.

The resolution of most commercial PCR tests is 4 or 4.5 log reduction. A log reduction (base 10) is a complicated way of saying you move the decimal place once. So a one log reduction is going from 100 to 10. A two log from 100 to 1. A four log reduction is going from 100 to 0.01. There was a reason that I started each of those examples from 100 and that is that the PCR test that we use for CML is (or should be) standardized so that the average person is 100% at diagnosis (generally they report as a % even though technically it is a count rather than a %). There is a bit of variation in this average but not enough to get worried about. Still it confuses many because they can be diagnosed say with 120%.

The first land mark in treatment is generally not from a PCR test. The first goal is to get to normal blood counts - CHR (complete hematological response). The second goal is to get to a complete cytogenetic response (CCyR) which means when they "look" at the marrow or blood and try to count the number of BCR-ABL cells they can't see any, or they get lucky and only see one. When you get to CCyR your PCR test would generally give a number of around 1% (which is a 2 log reduction, i.e. move two decimal places to get from 100 to 1). Getting to CCyR is something you definitely want to aim for as it is associated with a much better prognosis. The next two milestones are MMR (major molecular response) which is a 3 log reduction (PCR = 0.1) and PCRU (when you PCR result is so low it can't be detected) which is generally a PCR of less then 0.01 or 0.003 depending on the quality of the lab doing the test. All of the above numbers assume that the lab is using international standards, even though different labs do the test with a different control gene. The accuracy of the test i.e. the variation you can expect is plus or minus half a log so if you took two your blood samples on the same day and sent them to the same lab you could get a result that varied by up to one log e.g. one sample could be 1% and the other 10%.

[Trey]

PCR and other CML testing explained:

http://community.lls.org/docs/DOC-1273

[Barb@Anderson]

ThanksTrey and jjg, Trey, the site you sugggested was very informative although a lot of it was over my head.. Thanks to both of you for the explanation.  I am reading everything I can about this to try to understand more.  I just hope I am not losing time by experimenting with the Gleevec if in fact it has stopped working and I need to change.  I don't go back to him til May because he said he wanted at least two months of the adjustment of 400 MG Mon, Wed and Fri and 200 the other days to see if it was working to bring the numbers down.  Wow, that would be a bummer if the Gleevec has just stopped working and I have wasted two and half months fooling around with my health.