17 replies to this topic

[AnnieB]

Hi Trey,

I have posted on here before and have gone through quite a bit of info that you and others have posted on this board which has been very helpful. Thank you all very much.  I was newly Dx. CML +phil. in March of this year have been on 400mg G.  Dr. just did peripheral blood test last week went in today and he said that I was in remission and all my blood work was normal.  I got a copy of the cbc but they are going to send me a copy of the flow cytometry and BCR ABL FISH in the mail.  After looking at the repost it states that my RBC, HGB, HCT are all low and the RDW, EOS, and ABS EOS are high.  Also states that LEUK ALK PHOS SCORE is at a high of 212.  Have tried to look the last part up but having hard time getting the ans. anywhere.  My Onc. does not seem to be concerned about these, and sad to say I do not have much faith in him, so was wondering if you could give me any insite if I should be.  Also we are cutting my G. down to 200mg a day.  Thank you for any input you might have.

Angie

[Trey]

RBC, HGB, HCT are all low: It is common for this to happen with CML.  You have fewer red blood cells, and so also you have less HGB.  It is a type of CML induced anemia that many of us have, especially at first.

RDW, EOS, and ABS EOS are high: These show typical CML abnormalities with the blood cells.  (ABS means "absolute"; first EOS number is a %, and the ABS EOS is a total count).

LEUK ALK PHOS SCORE is high:  This is something you should pursue further.  Your Onc is wrong to ignore it unless he can explain it.  CML almost always causes a low LAP score, but yours is quite high.  It may be a secondary issue like infection or something else, so don't become overly concerned, but it should be checked out.  I would first have the LAP test repeated to make sure it is correct (it can have a a high failure rate), and if it is correct, I would ask the Onc to do additional testing to understand why it is high.   I assume you were properly diagnosed with CML -- do you have your lab results for BMB/FISH/PCR?  Let me know if I can help further.

http://books.google.com/books?id=L0B-lKtvI_UC&pg=PA75&lpg=PA75&dq=leukocyte+alkaline+phosphatase+(LAP)+CML&source=bl&ots=MrDET7naEQ&sig=eno5vFYvyYCuFGJE0Qm4CGkeqlA&hl=en&ei=EPMdSrWzGeWFmQfKtN3ABg&sa=X&oi=book_result&ct=result&resnum=3#PPA76,M1

I also do not understand why the Gleevec dosage is being reduced to 200mg.  That is not standard therapy.  If you have very low WBC, the correct option is a Gleevec break.

[AnnieB]

Trey,

Thank you so much for your reply.  A BMB was done on 2-13-09 which showed early CML with Ph chromosome.  Started the G. in middle of March 09 and the blood test results that I gave you were done last week.  They were going to send me the results in the mail of the FISH/BCR/ALB and Flow Cytometry.  He said the results of those's showed remission.  I was having very bad side effects from the G. so maybe that is why he cut back, not real sure, and as I have stated before not a whole lot of faith in my Onc.  Planning to move to different town within the next six months and I heard that they have a great Cancer Center there so was going to hold out switching Onc's until then.   My next appt. with my Onc. is not for 6 wks.  Should I be concerned enough about the high LAP to get ans. before that time?  By the way...I believe some of our Onc. should be consulting with you, and you should be getting paid for this..your are the CML specialist....

Thank you again...Angie

[DancingRain]

Trey, I have read your previous discussions on PCR and FISH values and you seem like an expert person to talk to. I still am a little confused about PCR values. I was diagnosed in Oct 07 and had my lab work done with Genzyme. Then this year, all of the oncologists switched to US Labs, so I am having to start all over again with my PCR values. I had a PCR done at Genzyme in Nov 08 and it was 0.004%. Then in Mar09 with US Labs, it was 0.017% and has been going up and down since then. I have had a PCR done every month since Mar. My BMB this month showed a FISH of negative, but the PCR was 0.297% if you add the two marker chains together. Genzyme used to add the 3 different enzyme chains or test together for a total, US Labs do not. Also Genzyme used different markers for their tests. I do not know which is more reliable, and am getting really confused about the whole thing. Do you know the differences in the laboratories? I have read in your discussions that there is no standard testing procedure. So how do I know what is true? We also tested for genetic mutations with Gleevec and found none, and my Gleevec blood values are normal.  Any guesses? I have thought about emailing Dr. Druker and asking him. Thank you for your reply!

[Trey]

I am not a medical professional and cannot provide expert opinions. I just try to point people in the right direction as best I can, if I think I can be helpful.

Regarding what you are calling your PCR "enzyme chains" and "marker chains", I assume the reason you are mentioning these is that you have more than one BCR-ABL breakpoint?  Otherwise you should not really care about that stuff.  The 3 main types of BCR-ABL are b2a2, b3a2, and e1a2.  If you have more than one breakpoint, the values in the PCR should be added together to get the total PCR result.  But they will usually be reported as separate numbers.  So you can just add them together yourself.  Is this what you meant?

Here is some more info on this issue:

http://ubb-lls.leukemia-lymphoma.org/ubb/Forum17/HTML/001433.html

If US Labs has a standard PCR log reduction value, they should provide that to normalize the results.  But I would monitor your PCR results closely, since they are rising by more than 1 log.  That could be a reason to either increase dosage or change drugs -- ask your Onc about these options, since that is possibly what a specialist might recommend.  If you believe your Onc is not qualified to handle your case, it would be wise to consult a CML specialist.  Dr Druker is certainly outstanding.  You can contact his nurse Carolyn Blasdel and she would be very helpful:

http://www.ohsucance...p&list=leukemia

http://www.ohsu.edu/...or.cfm?id=10931

[Trey]

If it were me, I would have a LAP re-test done now, then if it was still high, continue to try to figure it out.  Since a high LAP is unusual in CML, I would not wait 6 weeks to pursue it.  But again, it could be a secondary issue unrelated to CML.  I just personally believe in sorting out unusual issues when dealing with CML.

[AnnieB]

Trey,

Again thank you for your responce.  While you might not be a professional, the value you add to us here is ...  Dont seem to sound like the commercial but...Peace of Mind....Better Understanding....Your time and support....PRICELESS!!!!!!!!!!!!!   Your the Bomb!!!!

[kendavies]

So Trey,

Daughter Suzie has finally received, (12 months after diagnosis), her PCR, (supposedly a 9 month test, but which took the lab 6 attempts over 2 months to get a reading).

0.1%

At 6 months, (December 2008), it was 0.01%. A much nicer number and then seen by the onc as a 3 log reduction.

Looks like she is back at 2 log.

Please don't let it be a genetic mutation.

Her 12 month BMB is scheduled for next week which hopefully will show the trend and answer the mutation question.

What do you think about now pushing for a swap to Nilotonib, (within her clinical trial protocol), without waiting another 3 weeks or so for the BMB result?

PS.  Have you ever considered authoring THE definitive book on CML? That way you could just point us all, (patients, carers, med. students, lab technicians and even the oncs), to the relevant chapters without having to continually repeat yourself as we all flounder.

[DancingRain]

Thank you Trey for your support. You are correct in correlating the breakpoints. Genzyme used different markers than the ones you mentioned, which are the breakpoints that US Labs mentioned. My Onc has colleagues at OHSU and will contact them.  I believe that the next step for me is to switch to Sprycel. I took care of a patient that was on it and he seemed to tolerate it well. I have been reading other discussion boards to see how other are responding. I will look at the websites you posted.

I would really like to thank you for your hard work in providing support to the CML community. It is greatly appreciated!

DancingRain

[Trey]

Ken,

If you can trust the PCR numbers (you have pointed out that the history of her lab testing is questionable), then a 1 log increase is not the best news.  She could wait for another PCR, or switch to Tasigna now.  She has been 1 year since diagnosis.  There is a growing trend to switch drugs sooner rather than later.  If it were me, I would likely switch to Tasigna now.

[kendavies]

Thank you Trey.

One piece of news I've learnt from Suzie since my last post is that the nurse who rang her at work to drop the "bad news", told her a kinase mutation test on her last sample had shown no mutation present.

Prior to reading your ARUP link on kinase domain mutation testing, I wrongly believed a BMB was necesaary for this sort of test. Perhaps I was getting confused with chromosonal mutation testing.

Anyway, the nurse's comment has given some comfort but I am really puzzled as to why the PCR would go into reverse from a 3 log reduction to a 2 log reduction if there is no mutation.

Is this possible and what could be the cause?

Maybe a Tasigna switch will alleviate Suzie's major side-effect problem with edema.

Thank you again for being there.

[Trey]

CML does not play fair.  There is not just one reason for loss of response to drug therapy.  Researchers have learned that besides the BCR-ABL kinase mutations, loss of response can also be caused by over-expression and activation of LYN kinase in the CML cells, giving those leukemic cells superior survivability.  Bugger.

It seems that Sprycel is the better alternative when LYN kinase over-expression and activation is an issue. That may argue for dropping the clinical trial and starting Sprycel if switching to Tasigna does not work quickly.  If it were me, I would give Tasigna a quick try (couple months) then be prepared to switch to Sprycel and drop the trial if it does not work.

Another cause of lack of response can be low Gleevec absorption (previous Gleevec Blood Level testing shows Suzie has no problem there).  Otherwise, I am sure there are other reasons for loss of response to drug therapy that have not yet been identified.

A reasonable question would be how to test for LYN kinase over-expression/activation. It is not done as a standard test at labs.  She needs to ask her Onc about it.  (She may need to take an article along to describe the problem).

http://www.sciencedaily.com/releases/2008/06/080624174903.htm

http://www.medscape.com/viewarticle/576661

http://www.medscape.com/viewarticle/577901_4

[kendavies]

Thank you so much Trey.

This is scary. We were feeling relatively comfortable when she achieved a 3 log after only 6 months.

And now this.

I will certainly get Suzie to raise the LYN kinase suppression issue with her onc.

Thank you again.

[Trey]

Remember that it is still possible that her PCRs are not quite accurate due to the lack of adequate quality control processes by the lab where her testing is done.  So a next PCR could look better just due to lab variables.  It is even possible that her 3 log PCR was the one that was wrong (too low), so that she may not have even retrogressed at all.  The LYN issue may or may not apply to her case, of course -- I was just answering your question about causes of loss of response.  But given all that, a switch to Tasigna would not be a bad idea.

[kendavies]

Thanks Trey,

This has been exactly my hopeful train of thought.

The BMB should be illuminating.

I was not saying your information was scary. Just the whole "cancer has a mind of its own" scenario.

Your help always calms those thoughts.

Your blog (book) is incredibly impressive and I hate to think how much time and effort went into its compilation. It now has its separate icon on my desktop.

Again, my thanks.

[kendavies]

You were right, Trey, in saying CML does not play fair.

Suzie has now had the 12 month BMB and we await the results next week. Maybe they will show what on earth is going on.

In the meantime, the oncs conducting her clinical trial have now advised that the blood test late May showed a PCR of 1.0% and not 0.1% as told to her by the nurse on the phone.

That's a 2 log increase since she achieved a 3 log reduction, (0.01%), in December 2008 within 6 months of commencing Glivec.

Subject to ECG's and an Echocadiogram etc next Wednesday, she will be switched to Tasigna that day.

So frustrating, but thank goodness there are still drug alternatives.

[Trey]

I would suggest she get a copy of the kinase mutation test report to see exactly which kinase mutations it tested for, and exactly what the results were.  Not every mutation test is equal, since there are over 100 known kinase mutations.  And the lab has not shown a history of excellence and quality control, so I would double check all lab reports to make sure the correct drug is chosen.  Sprycel and Tasigna each have their own strengths and weaknesses if a mutation is the cause of loss of response.  Otherwise, Sprycel seems to be better for LYN over-expression.  Both the kinase mutation issue and LYN issue are discussed in the following article:

http://www.cmlsupport.org.uk/?q=system/files/Mechanisms+of+Resistance+-+Imatinib.pdf

But starting Tasigna next week while continuing to figure this out would be a reasonable option.  Gleevec is obviously no longer working, so a drug change is needed.

The BMB results may possibly be helpful, but unlikely unless there is a second chromosome abnormality.  It will not help shed any light on the kinase mutation or LYN over-expression issues.  So we would hope for no new info from the BMB.  It could possibly be slightly positive for BCR-ABL, although it would have previously been negative when the PCR was down low, since it only checks 20 cells.  Hopefully a FISH and/or PCR was also done on the aspirate fluid.

[kendavies]

Trey,

You will never know how much I gain from your interest, knowledge and support. I've read all you have said and also the linked documents.

Saying "thanks" just doesn't seem enough.

At this stage, Suzie's oncs in charge of her trial have not spoken directly to her and she probably won't see them until the ECG's etc starting Tuesday.

She will then be asking more about the kinase mutation tests and will try to get copies of the reports.

In the meantime, her referring doctor, (who is a relative), has gleaned for me from the main onc that "there are no clinical worries, she is still in CCR and, but for the clinical trial, she would be staying on Glivec which is still doing its job". Apparently, the only reason for the Tasigna switch is the fact that these retrograde readings "fit into the trial protocols for a switch".

"Preliminary results from the BMB show her marrow is still morphologically correct". "The molecular results are still to come". "There is no evidence of mutation"."There has not yet been any direct onc contact as they are not concerned but actually pleased with her results".

I certainly like hearing this but it all seems a bit vague and contradictory and a bit too comforting. However, fatherly intervention can only go so far.

Knowing the Tasigna switch is just 5 days away, Suzie is very tempted to cease the Glivec, (and her Grade 3/4 edema side-effect), in the meantime. The onc's secretary has said the trial protocols do not spell out whether this is permissable or not. I wonder if there is much risk involved?

I will post again when more information is obtained.

Thank you again for being there.