39 replies to this topic

[random]

!!!===== APRIL 2011 was the actual date of this thread. I've edited thread subject and that's why it shows the actual date.===

Happening in APRIL 2011:

----

Hi everyone.

One of my friends has CML. On his latest blood test, the leukocytes are for about 4800 and the Philadelphia chromosome is present for 90%. Is this a sign of progression of the disease?

He's taking Gleveec for 5 years.

And, another question: if the Philadelphia chromosome is present but the leukocytes are small, can the disease progress?

[Trey]

The 90% after 5 years is not good.  But a different drug may resolve the issue.  Your friend needs to see the Onc right away about switching drugs.

"if the philadelphia chromosome is present but the leukocytes are small, can the disease progress?"

Yes; the WBC is independent of the "percentage" of leukemic WBCs.  The percentage is more important when it comes to assessing response to therapy.  90% leukemic cells is not good even with low WBC.  The WBC would eventually rise very quickly under these circumstances if the treatment is not changed to a drug that works.

[random]

Trey, you mean - my friend is in the CML accelerated phase now?

PS: When 90% discovered, he took 2 Gleevec pills. Now onc has increased treatment to 4 pills.

[valiantchong]

Hi,

Normaly drug given in 100mg per tablet or 400 mg per tablet. As for a patient when diagnosed, the doc normally prescribe 400mg dosage per day and track the response for CBC for monthly or once in 2 weeks when start of diagnosed. For an average individual if under 400 mg/day, one will achieve CHR in a month time, meaning the WBC is under control < 10.5. If the person response to the drug well, he will achieve MMR in 6 months to a year. If one response very wll he could achieve CMR (no PH+ chromosome detected) within a year or less, some achieve PCRU in 2 years time, but only few ppl will achieve this.

As your friend he is still 90% of PH+ meaning the drug only control in CHR phase or complete Hematological response or mean WBC in control. There is a milestone to track the progress of the prognosis.

Normally the doc will recommend to increase the dossage to 600 or 800 mg if the patient failed to response to the drug to achieve MMR or CMR in the timeline given. Or some doc will switch drug to 2nd generation TKI like Sprycel or Tasigna.

[hannibellemo]

We don't have the right kind of information to tell you what stage your friend is in at this point. He would need to have had a recent BMB and his doctor could easily tell at that point. The number of pills he takes isn't really helpful either, it's the number of mgs. per day that he is taking that is important.

No matter how much Gleevec he is taking now it sounds like he needs to be on a different TKI and the sooner the better. I would suggest he talk to his doctor about Sprycel because its mechanism is totally different than Gleevec.

Is that drug available to him?

Good luck, you are a good friend to be so worried for him!

Pat

[Trey]

As Pat said, there is not enough information.  The friend needs to switch to a different drug, not just take more of the same drug.

[random]

Thank you everyone for your answers.

I will keep in touch with you and post the health evolution of my friend.

Feel free to post any advices.

[CallMeLucky]

You need to specify the milligrams of the pills.  Something doesn't sound right.  Gleevec comes in 100 mg and 400 mg doses.  So he was either taking 200 mg per day and now 400 mg per day or he was taking 800 mg per day and now 1600 mg per day.  Since the latter is really not conceivable, the first case seems to be the likely scenario.  If that is the case, then your friend was under-dosed and that could possibly explain why he is not achieving a good response.

A move to 400 mg could make a big difference, but the question needs to be asked why was he only getting 200 mg.  If this was by choice of the doctor, then he needs a new doctor.

I'm making some assumptions here, but something about this doesn't sound right.

Best of luck

[random]

Guys,

Thanks so much for your informations.

Find out some new informations about this:

- He was taking 200mg of Gleevec when 91% (this is the exact value) of PH+ was detected. He started with 400mg/daily at the begining (100.000 leukocites detected at the first medical results)

This was the onc's decision about decreasing the dosage.

Now the onc has increased again to 400mg/daily of Gleevec.

Willing to know your opinion about this. Should he change the doctor? Does this makes any sense?

[hannibellemo]

How long was he on the 200 mg.? That is below therapeutic level and unless there was another reason to lower the dosage for a short period of time (not five years!) he should have been taking 400mg. per day. The guidelines are that your friend should have reached Complete Cytogenic Response (CCYR) by one year, definitely by 18 months, or been switched to another drug - Sprycel or Tasigna.

He should be getting frequent PCR testing (3 - 4 times/year) to see how the BCR/ABL is responding to his drug.

I gotta say, I wouldn't stick with a doc who doesn't appear to know what he is doing, but, again, I don't have much to go on here.

Pat

[Trey]

200mg is not enough unless the Onc was treating very low blood counts.  If the 400mg does not have an effect in a month or so, he needs to change drugs.  Or else change drugs now.

[CallMeLucky]

You asked if he should change doctor.  I can tell you that I would be very wary of a doctor who chose to treat CML with 200mg of Gleevec.  I think he needs to have a very frank discussion with the doctor about why that decision was made.  I have not seen anywhere in the treatment guidelines where 200 mg dosage is advised.  My understanding is that it just isn't enough.  Perhaps as Trey said, with low counts it could be something they try, but I would expect that to be for a very short duration.  So the question really is why that dosage?  If the doctor doesn't have a very good reason I would find another doctor (even if he did have a good reason I would still question it to an extent, but you have to look at how the relationship with the doctor has been overall and what your confidence level in him is).  I would question how many CML patients the doctor has to get an idea of his experience treating CML.  Depending on what you have available to you, it would probably be worthwhile to get a consultation with a CML specialist to review his case and get a definitive treatment plan.

Best of luck

[random]

Your feedback is platnium-valued for me. Thanks so much guys.

I'll talk to my friend and tell him what you said. I'll go to the doctor with him and ask some questions.

Here are some results provided by my friend:

- 400mg - 6 months
- 300mg next 4 months
- 200mg next 6 months (WBC ~ 2.5)
- 200mg / 100mg next 2 months (WBC~ 2.7)
- 200mg 2.5 YEARS (WBC ~ 3.0)
- 400mg in prezent

Initial results:

- WBC 120.000
- RBC 3.49
- HGB 9.9
- PLT 838

Current results:

- WBC 2.1
- RBC 2.68
- HGB 9.4
- PLT 97

Tell me what you think please.

[CallMeLucky]

Blood counts are not enough to tell what is going on.  It looks like he is having low counts and that is why the doctor reduced dosage.  We need to see his FISH and PCR test results over this time frame to understand what is going on.  Despite the low counts, 200 mg Gleevec is usually not going to be effective, as evident by the fact he has such a high percentage of leukemic cells even after being on therapy for a few years.

Do you have results of FISH / PCR?  Has he had bone marrow biopsy done?  What were the results of those?

[random]

As a n00b, please tell me what is FISH / PCR abreviations are? To know what to search for?

[CallMeLucky]

FISH and PCR are types of tests.  Blood counts are superficial and only tell a little of the story.  The real tests to see how you are responding to treatment over time are molecular tests that look at the cancer cells.

There are four types of tests CMLr's tend to get.

The Complete Blood Count (CBC)

Cytogenetics/Karotype

FISH (Fluorescence In Situ Hybridization)

PCR (Polymerase Chain Reaction)

The CBC looks at blood counts and are used to track first milestone of treatment where counts go back to normal.  This is known as a Complete Hematological Response (CHR).

The Cytogenetics tests are usually bone on bone marrow fluid extracted from the hip during a bone marrow biopsy or aspiration.  This is usually done at diagnosis, then again at 6 months and 12 months.  From there it depends on how things are going to see if they are going to do it again.  With the test a Cytogeneticist will review cell samples under a microscope and look for the Philadelphia Chromosome, whish is the leukemic cell.  This test usually looks at 20 cells.

A FISH test is somewhat similar to the traditional Cytogenetics test in that it looks for the PH+ chromosome.  It is a more powerful and advanced test.  Usually this test looks at 200-500 cells to determine a ratio of healthy cells to PH+ cells.

The PCR test is the most sensitive test we have and it is used to look for BCR-ABL.  BCR-ABL is the cancer gene caused by the PH+ chromosome.  PCR test is very sensitive.

FISH and PCR should be run at dx and then every three months during the first 12 -18 months of treatment.

If treatment is going well then these test results should be going down and hopefully coming back negative.  When the Cytogenetics/FISH tests come back negative for PH+, that is considered a complete cytogenetic response (CCyR) and that is a major milestone and goes a long way towards long term survival.

With the PCR test we look for something called a log reduction, which is essentially a ten fold decrease in the amount of BCR-ABL detected in the test.  So in my case I had PCR 1.2% at diagnosis.  My last PCR was .0081.  So far this is good progress and essentially a three log reduction.  A three log reduction is considered a Major Molecular Response (MMR) and this is another important milestone.  Beyond MMR an individual can reach CMR which is a complete molecular response, also known as PCR undetectable or PCRu.  Some people will never reach that, and that is okay.  Long term survival has not been shown to be impacted by reaching PCRu.  A stable three log reduction appears to be good enough.

One thing to keep in mind with PCR tests is that the way they are run varies from lab to lab, so you can't compare results from one lab with results from another.  The thing to look for with PCR is a stable downward trend over time.  Some labs have adopted an International Scale to try and make it so results can be compared across labs, but not all labs do it.

You need to get copies of all the tests and see what the results have been to understand where he is.

If you can get them and post them here, we can help you to understand them.

Best of luck.

P.S. - your friend is lucky to have someone looking out for him the way you are.

[LivingWellWithCML]

Hey all,

Great info as always.  Just curious, how do you read a PCR result?  Mine from a bone marrow test @ diagnosis is called "BCR-ABL1 Quantification: Ratio of BCR-ABL1 transcript to G6PDH transcript".  But there are two numbers stated with this:

• Ratio: 2.5E-01
  
• Log Change from Baseline: 0.50
  
• Percent: 312.50%
  

Of course, this was my first PCR so the results ARE the baseline, so I'm confused on what that percent value really stands for.  Is my baseline PCR actually 0.25?

Thoughts?

[Trey]

Your ratio: 2.5E-01 implies a percentage of 25%, but you said the report says 312% -- maybe you should quote the text verbatim.  You say the Log Change from Baseline is 0.50 -- log changes can be positive, especially at diagnosis, if using the International Scale.  Not enough info to answer.

[hannibellemo]

Random,

As a newbie you really need to read this. Everything you ever wanted to know about CML...by Trey (in 3 easy parts)

http://community.lls...mpiled-postings

http://community.lls...ctions-j-thru-s

http://community.lls...ctions-t-thru-z

This is done like a dictionary so look up FISH under F and PCR under P. etc., etc.

Good luck!

Pat

[LivingWellWithCML]

Trey - thanks.  Weird, that's literally all the report says in that section.  I think that (ratio * 100) is the starting number ... so 25%.  I'll ping the doc to make sure I'm reading it right.

Appreciate you responding -

Dan