12 replies to this topic

[dolphin]

Hi everyone,

I have nt posted in a while, I guess had become quite relaxed after my mother's last PCR test in Jan'12 which was 0.6%. However we did her test again last week and the report came in today. I was shocked to see her pcr at 13.39 %. I will be taking the doctor 's appointment for tomorrow but till then i was hoping to get some answers here.

She was diagnosed with cml in sep 2010 with the following dosage and PCR results :

Diagnosed in Sep'10, Gleevac started on 28th Sep '10

PCR in Jan '11 - 17%  (400mg Gleevac)

PCR in May'11 - 12.35% (dosage increased to 500 mg)

PCR in Oct'11 - 12.5 % (dosage increased to 600 mg)

PCR in Dec'11 - 0.3% (dosage on 600mg)

PCR in Jan'12 - 0.6%

PCR in May'12 - 13.36% (Between the months of Jan '12 and May'12 , she has been slightly irregular with her dose due to nausea and flu in India; nevertheless she has taken 400 mg most days and would have missed the dose completely may be twice or thrice)

I am worried that does that she has developed resistance to the disease in these couple of months or she needs to be regular on 600 mg to control the disease.

From everything that I have read , once a patient reached under 1 % PCR then the chances of disease progression or resitance are very low. Is that so ?

Are there any people in this forum whose PCR would have shot up so drastically and then came back down..

.

I am very disappointed with my doctor her in India, after her 0.6 % pcr he asked her to reduce her dosage to 500 mg . i was nt completely conviced with this so I had posted in this forum in Jan and another group that I am part of . And they all said to continue on 600 mg so she as been taking 600 mg on and off

Trey, I am hoping you ll be able to help me her with the next few steps.

Hoping for some answers before doctor's visit tomorrow.

God Bless

Surabhi

[cberwick]

Hi Surabhi,

Gleevec/Gleevic at 400mg is a maitenance dose. It sounds like your mom has lost her response and most likely needs to switch to one of the 2nd generation TKIs (Sprycel or Tasigna).

How are her other numbers (CBC)?

What did her doctor say?

Chris.

[Happycat]

Surabhi,

The 600 mg seems to have been working, certainly better than 400 mg. She may have lost response, or she might have efflux issues (cells kick the drug back out before it can do its job).   Some people, maybe 10-20%, have efflux issues, if I am remembering Dr. Druker's video presentation on YouTube correctly. The videos are worth watching if you have the time. He does one on people who lose response, and what some typical reasons may be. I'm just intrigued that your mom didn't show response until she hit 600 mg, which makes me wonder if efflux could be a problem for her.

HTH,

Traci

[pamsouth]

The oncologist may not want to increase her dose because of her other counts, and organs which are important too.

What is her age? She also seems to be having other health issues, that might be another reason he doesn't think he should raise the dose.

Is the high dose of Gleevec making her sick.  I mean sometimes you have to see what level of dosage the patient can tolerate.

Also if she has had the flu, that will raise your white counts.  Because when you have the flu the white cells need to come out and fight.  Even though the BCR/ABL is not normal, they still do function.  I think maybe you should ask some more questions of your doctor.  Maybe there is a much bigger picture that he is looking at that you are not aware of.  I don't know how in India things work on the doctor/patient communication.

PamSouth

[Trey]

Some people need the high dosages just to maintain the response, and even small variations can affect the results for those people.  Your Mother seems to need the higher dosage and should continue to take the 600mg.  As for when a person is safe from resistance or progression, if the patient can make it a little over two years without resistance, then the chances of resistance drop to a very low level. 

[dolphin]

Thanks Trey, appreciate your response ..

But do you think a little variation in the dosage can make her pcr jump ..

Also ideally should we be shifting to the second generation drugs ..I have read that have a lot more side effects related to the heart .. ?

What should be our next step ..? Our doctor has asked us to get the mutation analysis and till then continue on 600 mg ..

I know silly question but does this look like resistance to you .. I am feeling really an anxcious while waiting for the results for the mutation analysis ..

[Trey]

The recent PCR was not good news, but another PCR is needed to confirm a loss of response.  So I do not know, since PCR tests are not always accurate.  So another PCR would be the preferred next action.  You would also want to confirm that the most recent PCR was done at the same lab as the previous ones. 

"Resistance" can be caused by several issues, not just kinase mutations.  The Kinase Mutation Test is a good idea, but only 1/3 of TKI drug resistance is caused by such mutations, so it is not a definitive test.  Repeating the PCR is the proper way to show loss of response, or drug resistance.  A FISH test could also be used.  If either test confirm a loss of response (drug resistance) which includes loss of Complete Cytogenetic Response (CCyR) then a Bone Marrow Biopsy should also be done.

If the other TKI drugs are options for her in India, then switching drugs would be the best approach.  If the cost is very high and must be considered, then 800mg Gleevec may work.  But if it were me, I would switch drugs.

[niciop]

Trey, You seem to know quite a bit about PCR reports.  I have AML, not CML, diagnosed in Feb. 2011.  I am not getting Gleevac, I guess it is not effective with AML.  However, I have had 9 rounds of chemotherapy (including induction) and they are monitoring my PCR.  My doctor wants me to continue chemotherapy to try to get my PCR to 0.  My last PCR was .02.  No one on the AML blog knows anything about monitoring with PCR, but I see it is done with CML.  Do you know if it is possible to get a PCR of 0? 

[Trey]

PCR can be used to monitor low levels of leukemia, and is the most sensitive test available.  For CML patients the PCR looks for a product of the CML genetic translocation (mutation).  For AML, there are numerous sub-types, and therefore numerous types of PCRs.  But in general, when the PCR shows as "zero", the disease will be at a low level but the patient will still have approximately 1 million leukemic cells in the body.  So you should understand that zero is not really zero.  That may impact the decision process regarding target PCR levels.  Regarding whether it is possible to get to zero with chemo, it certainly is, although it may be sometimes kill off most of your good blood cells at the same time.  I am not able to say whether it is the right choice or not, just trying to provide some info so you can ask your Onc some questions.

So your last PCR was .02, but that does not tell you how close to undetectable you are.  Undetectable may be less than .0001 depending on the PCR test for your type of AML.  So I would ask your Onc how much chemo it would take to get to PCR undetectable.  And ask the Onc about probability of relapse at your current levels vs. probability of relapse at PCR undetectable.  That should help you make a decision.

http://www.texasonco...eloid-leukemia/

[niciop]

Trey, thank you so much for taking the time to respond!  I visited the link, and although some of the information was outdated (1995 New England Journal of Medicine reference) I appreciated the information about AML t(8;21) which is the subtype I have.  I was surprised that when the PCR shows "zero" there are still 1 million leukemic cells!  I have 3 different opinions from different oncologists, so it has been confusing to determine the best course of action.  I am unusual in that my AML is a "secondary" cancer from previous breast cancer treatment.  One oncologist is pushing me to have a stem cell transplant, another wants me to keep trying to get my PCR undetectable.  One onc tells me that if my PCR is undetectable, I have a 70% chance of remission, another onc tells me that a relapse is inevitable regardless of PCR.  I have already had 9 chemotherapy treatments, which my husband worries will damage my organs.  I will continue to try to educate myself as much as possible to make a decision, but it is scary, because my life is at stake!   I hope your treatments have gone well. 

[Trey]

The relapse rate for AML is fairly high since the chemotherapy cannot be administered in high enough doses to kill all the leukemic cells without also killing off the good blood cells.  Essentially, the goal of chemo in leukemia (except for BMT preparation chemo) is to try to kill of the originating leukemic cells and stop the leukemic process without killing too many good cells, but this is a "hit or miss" proposition with no way to know if it was successful until relapse either occurs or does not occur.  It works better for some types of leukemia than for others.  Since this process uses somewhat "lower" dosage chemo, it is often unsuccessful.  During preparation for a BMT, very high dose chemo and radiation are used to kill off (hopefully) all white blood cells -- both leukemic and non-leukemic -- including the stem cells, and start again with a new set of blood making stem cells from a donor.  The literature suggests that t(8;21) AML has an overall relapse rate of about 30 - 40%, and higher if there are any high risk factors involved.  So it is not an easy decision, since both choices include significant risks. 

So the questions for your Onc might include:

1) What is my probability of relapse, with or without more chemo?

2) What AML high risk factors do I have, if any?

3) Should I look for a possible donor, if not already being done?

4) If I were your wife, what would you recommend?

Here is a paper titled Bone Marrow Transplant, Introduction and Basics that might be useful:

http://community.lls.org/docs/DOC-1375

AML t(8;21) detailed description:

http://www.hindawi.c...bb/2011/104631/

PCR for AML t(8;21):

ajcp.ascpjournals.org/content/125/2/267.full.pdf

[niciop]

Trey, Thank you so much!  You have been a wealth of helpful information!! I am SO conflicted!  As far as the questions:

1) What is my probabilty of relapse, with or without more chemo? All oncs say inevitable relapse without 0 PCR, one says inevitable with a 0 PCR, one says 50/50 with 0 PCR, one says 30% with 0 PCR

2) What AML high risk factors do I have, if any?  Seconday AML is a risk factor, previous intense chemo & radiation for aggressive breast cancer (2009-2010), 9 chemo treatments for AML, older age (60)

3) Should I look for a possible donor, if not already being done? I have a 10/10 match and a spare at MD Anderson.

4) If I were your wife, what would you recommend? My main onc tells me that he is working hard to make the best decisions for my survival, would consider it a personal success or failure depending on the outcome of my case. He is the one who thinks my relapse would be 30% (70% chance of remission) with a 0 PCR, wants to get me to 0 with more chemo.

I still struggle with what to do!  At first, I was leaning toward BMT, but some of the info in the Texas Oncology link you sent me stated that waiting for a BMT until a relapse is not unreasonable with t(8;21).  I know a BMT is my best chance for a cure, but the transplant doc at MD Anderson predicted about a 30% mortality in my case.  That made me want to keep trying with the chemo.  But my PCR is not 0 and the transplant doc implied that constant chemo is not a good idea if I am going to have a BMT.  So now I don't know if I should wait until a relapse to get a BMT!

    I was in a study at MD Anderson that started out with Mylotarg, which showed promise as an AML drug.  But before I could receive it, it was removed by the FDA.  So I received the ususal chemo drugs used for induction & consolidation.

    Anyway, you seem to be very knowledgeable and I appreciate your time giving me information and helpful links! If you have any other thoughts or opinions, please share them!  (By the way, I have a son named Trey if that is your real name). Thank you again!

[niciop]

Trey, Your article about Bone Marrow Transplants was very well written and easy to understand.  Those of you with CML are very fortunate to have Gleevec and other drugs to avoid the BMT while those of us with AML are not as fortunate.  I don't understand the biology well enough to know why Gleevec works with CML and not AML.