20 replies to this topic

[scuba]

Trey - buddy - this is for you:

WBC:  2.3 (last week = 1.9)

ANC:  0.85 (last week = 0.65)

PLT:  221 (last week = 234)

AND ..... my FISH came back.  0 cells detected.   According to FISH I have zero cells detected for bcr-abl out of 200 cells measured.

Now this is something ... I am still waiting for the PCR results.  I have been 7 weeks with no TKI whatsoever with FISH at 53% and after only two weeks of Sprycel - low dose at that (70 mg instead of the normal 100 mg) back in January and now my blood seems to be normalizing. 

I have not heard back from the Onc's yet, but I bet they want to do a bone marrow biopsy and take a close look.  That or use me for a paper.

For what it is worth Trey - I don't believe I am some miracle case.  I still believe I have CML.  For whatever reason it is going dormant.  The stem cells are probably quiet and the Sprycel gave my system just enough punch to allow my immune system to get ahead of it for now whereas Gleevec couldn't do it.  It must be at the Pluripotent stem cell level (higher up than what Gleevec affects).   At least that is how I am interpreting the results. 

For everyone else - once you get a CML diagnosis - there is no going back.  I will always have blood tests and have to track this for the rest of my life until they truly get a "cure".  But this sure feels nice to know that I can be without TKI's for awhile - maybe years.  Let's see what the transcripts show (PCR).

It must have been the Curcumin, or the Goji berry juice or the extra vit C and B that my wife has me take now.

Or it was the French kissing.  I am very good at that.  Very good.

[valiantchong]

hi,

congrates... u should celebrate at the zero club,,,,,good luck,,,,

[scuba]

No celebration ... I want to understand why my FISH went to zero in the absence of a TKI.  I still have to wait for the PCR results.   But I do suspect that Sprycel did something dramatic in my blood.  I suspect temporarily - but that's o.k. by me.  For whatever reaseon, the CML stem cells have gone dormant.

[Tedsey]

I got worried when I heard that your FISH increased on Gleevec.  I am thrilled to hear that it is now 0!  Wish Sprycel worked so quickly for me!  But, it did bring me to CCR within 3 months (but I may have been headed that way anyway on G).  Nevertheless, my PCR was still high in comparison to people on this board (but it went a little lower).  Hope your PCR comes out PCRu!  That would be a miracle!  Wouldn't it be interesting if "breaks" are very instrumental in getting the body to kick in to fight the CML by itself?  Pretty outrageous thought, eh?  Probably not.

How long were you on Sprycel again?  Not very, right?  Incredible that it worked so fast.  Cannot wait to see the PCR result.

Teds  

[scuba]

Hi Teds ....

I was on Sprycel for a total of 2 weeks at 70 mg.

I have no idea why my FISH went to zero, but I suspect my immune system may be functioning better and "mopping up".

All I know is that on Gleevec not much was happening at the molecular level.  Sprycel works differently and for all I know works for me in a very powerful way.

When my ANC counts get back to 1.0 and above, I have a big decision to make about going back on Sprycel.  It all depends on what my PCR level turns out to be.  I'll know that in a week or so.  If my PCR has dropped orders of magnitude (1, 2 or more log reduction), then I will stay off Sprycel and track monthly.  A de-facto trial. 

Apparently I had no good cells to speak of when this adventure began - but my body is now making them?  That is clearly what the FISH is showing.  Gleevec was not sufficient.  It gave me relief from 'disease', but did not battle the bcr-abl sufficiently.  Sprycel was potent enough to drive me into severe myelosuppression from which the CML itself is not recovering.  But my normal cells do seem to be re-populating.

Perhaps now I am a recovering CML'r - and my body is getting rid of the residual on its own (RCT will weigh in on this point) and slowly re-populating my WBC's.  Like Dr. Cortes said, my pattern of recovery is that of a stem cell transplant.  Fascinating.

This is a topic for another thread - but I believe many in the general population have bcr-abl genes come into being as a function of normal cell division and biochemistry.  The level of bcr-abl in the blood is probably below detection for most.  And the human body identifies it and defends against it.  All normal.

And then for some of us, we lose the ability to defend against the bad gene and it grows unchecked until we are sick or we have a blood test.  The TKI's don't eliminate CML, but TKI's do let us cope with it.  In my case - maybe - just maybe - Sprycel enabled my normal system to get ahead of the disease with Sprycel reducing the enormous burden in my blood at the higher stem cell level (not THEE stem cell that starts it all, but the ones tied to Neutrophils).  I have always had a problem with just one line of cells ... although my platelets jumped after I went off Gleevec - and they did not jump after going off Sprycel.  I am impressed with Spryce;.

Pure speculation - but I believe that if our immune system can be reset (t-cell; nk cells) to identify bcr-abl and kill it - then we have a cure.

I do not think I am cured, however.  I think I am heading into a natural remission as part of a cycle.  All Sprycel did was get me over the hump.  I suspect the bcr-abl stem cells are quiescent right now.  And if that is truly the case then drug breaks for many may be what is in our future and we don't have to stay on these TKI's like we are told to do so now.  I do believe that if I stay off Sprycel, eventually my bcr-abl counts will come back.  But when - in six months, two years, 10 years....?

Right now my FISH = zero.  Perhaps someone would like to comment on what they think it means.

[valiantchong]

Should celebrate you CCR... If your PCR results come out negative then CMR.... good for you... should think positive.. may be spontanous remmision... may be u are cured.....keep us posted interested in what Dr. Cortes theory behind this... should u join the STIM trial ?

[scuba]

V,

I am not cured.  I have had an "interesting" response to a very short term low dose Sprycel exposure.  Dr. Cortes wants to see me immediately and re-test to confirm (make sure it is not lab error) - but did say that he has little doubt that the current tests are correct (especially for FISH)  because my myelosuppression recovery is following a stem cell transplant profile.

For whatever reason - CML in my body is decreasing without TKI being present.  This is very different than those who are PCRu and go off medication - many of them relapse.

But at least bcr-abl is going down and not up.  Why it is going down is a mystery right now.  Could be natural defense (I have not read that anywhere) or it could be the Leukemia going into a quiescent phase (bcr-abl stem stells not dividing) - which is what I suspect is happening personally.

[Trey]

The repeat of the FISH test is a good idea.  But if it is accurate, the result is interesting so far.  But it is still too early to tell.  The curcumin combined with the Sprycel could be an interesting combination worthy of further study, since curcumin has shown some ability to impact CML cells, but not very effective on its own.

[scuba]

Trey,  what an odyssey this has been.  I really thought I would take 400 mg Gleevec every day and that would be it.

But my disease symptoms, Blood counts and reaction to TKI's has been anything but normal.  I also have not had the side affects most complain about.

Especially with Sprycel (although it is a lower starting dose and may explain) - no headaches whatsoever.

It's possible that I have a residual capacity to defend against the aberrant gene.  From Dr. Cortes perspective I am not within his experience.  He has not seen this before (although he has seen spontaneous remission prior to treatment (the Jamaica type)).

The good news is that I am not getting worse.  I look forward to the PCR results next week and follow-up with MD Anderson.  I bet he is going to try and talk me into a bone marrow biopsy and an immunological protein test.

[Trey]

I would want every test they could perform: BMB, flow cytometry, rectal leakage flow test, whatever.  More data is good when the situation is unusual.

I would put you under the category of a blind squirrel finding an acorn.  You just don't know if it is repeatable.  Happy hunting.

[PhilB]

Congratulations Michael - truly wonderful news.  Given the extent to which the Sprycel seems to have instantly machine-gunned your Ph+ cells it's scary to contemplate what might have happened if you'd been nearly 100% Ph+ at the time you took it rather than 53%!

[scuba]

PhilB - I gather that is why Dr. Cortes wanted my CBC's checked once per week (which I thought was too often) as I started the new drug.  He mentioned that if Sprycel was going to work for me - it will have dramatic effect fast.  He expect CCyR in 3 months.

I just received my PCR test results and it shows the same level as in January (35% - International Scale) - so I am not out of the woods by any stretch.  But it is good to know that Sprycel is so potent for me.  I have a suspicion that when I go back on Sprycel (and I surely will), I won't have as severe myelosuppression.  I have more normal cells now.  And perhaps I won't need as high a dose (maybe 50 mg. is enough).  Like a race car - have to do the fine tuning for all of us individually.

[PhilB]

I have to say I am intrigued as to how there could be such an enormous discrepancy between the FISH and the PCR.  Any thoughts Oh Mighty Treymeister?

[scuba]

My own guess is that the 'fewer' cells are producing a lot of transcripts which is what PCR measures.  I find it interesting that my body is not responding to the level of transcripts as measured by cell counts (my WBC's are only slowly rising).

It is an interesting set of data - assuming it is correct (re-test will verify) - it tells me that I have CML and that I have to continue treatment somehow.  The only good news I take from this is that I am growing a normal population of non-leukemic cells from which I should be able to better withstand myelosuppression so I can stay on therapy to get the 3 log reduction you all celebrate so much.  FISH is encouraging, but a dramatic drop in PCR will tell me that I am heading into remission.  When I restart Sprycel, I expect my ANC to drop, but not as much and I might be able to stabilize and continue treatment.  If my ANC goes too low again, I expect it will take longer than 2 weeks to cause it and when I test for FISH/and or PCR - that my PCR numbers will be that much lower.

In the mean time - I sure am on a roller coaster - the so-called watchful waiting.

[Trey]

In this specific case I believe the PCR more than the FISH.  I don't trust that FISH result since it does not make sense in view of all the other data.  I would like to see a marrow aspirate FISH rather than a blood FISH in this particular case.  For PCRs a blood PCR is fine, but a FISH requires numerous dividing cells* (progenitor cells), which prefer to live in the marrow.  So during severe myelosuppression the FISH result may be way off due to the lack of dividing cells in the blood.  So I would guess that the FISH shows severe myelosuppression more than an unexplainable prolonged stupendous drug response.  There are always variables, such as the curcumin, but that is a long shot; and especially in view of the relatively poor PCR result.  And the FISH test could have been a lab error.  I just did not want to jump in and ruin someone's party (at least until they were in the hangover stage).

[Note: Since this issue was questioned later in this posting, I mean those cells capable of dividing, as shown by the parenthetic "progenitor cells", not whether they are resting or dividing, i.e., in interphase or metaphase.]

[cherylannes]

Congratulations Michael!!!

I do not quite understand the PCR being at 53%  OOPS I MEAN 35%  and the FISH 0, but to be honest, I am almost more inclined to trust the FISH.  The reason being is that they are testing more cells with the FISH from a cytogenetic point of view, not the case with PCR.  With PCR there is so much chance for contamination, even every slight shake of the vial with the specimen in it can virtually cause problems.  I say, this because I sat in two PCR labs and watched technicians do them, then I actually did a PCR myself under supervision (on a animal specimen).  It is a very tricky thing to do...

All of these tests are not currently standardized so that makes it all the more complex.....

When my counts were severely wiped out by IFN (so long ago) my FISH can back 0, it took a few more months but my PCR came back as undetectable eventually....

What I get from this is that you are a god candidate to, one day in the future, be part of a discontinuation trial that will surely happen out at MD Anderson.

Fingers crossed, in the meantime - enjoy the drug free break.  Any indicaiton when you need to re-start the drug?

By the ACAI fruit is another good thing, and Feverfew too.  I buy the frozen ACAI pulp at my natural health food store and make a nice smoothie with it..

Additionally, from what I had herad, I think curcumin works better if dissolved in coconut mil????

Happy Day's!

Message was edited by: cherylannes

[scuba]

No party ruined - I don't disagree.  But it is still an interesting result and one that has Dr. Cortes attention more than normal.  And I don't have "severe" myelosuppression anymore.  The test was done after my cells have gone back up (i.e. out of the danger zone).  I always thought that FISH was done on interphase cells anyway.

Regardless - I want to get back on Sprycel as soon as I get above 1.0 to get the PCR numbers down.  I have a suspicion Sprycel works very well for me - I just have to have enough good cells to take the hit.

I would have believed in miracles if my PCR was 2 - 3 log down.  That would have been more impressive.  So we'll go on to the next step - which is still, watchful waiting - no stim and take the drug when I can.  At least it will be low dose (i.e. minimal side affects).

[scuba]

Cherylannes - PCR is not at 53% .... it is at 35% - that's a big difference in my mind.

I too believe the FISH - after all they specifically are using interphase dividing cells.  I read that FISH is more accurate early in the disease than PCR and PCR becomes the only way to go when FISH goes to zero.  Dr. Cortes is not concerned.  He has always said, I have something strange going on and he finds it "interesting" and "uncommon".  Now he wants to learn more...much more.  He's cleared his schedule to fit me into his lab next week.

Once my ANC gets above 1.0, I suspect I will restart Sprycel.  It's possible they may wait until 2.0.

They are curious if I have developed an immunological response to CML - they want to check something else in my blood (this was over the phone and I can't recall.)   Regardless of the FISH / PCR - my CBC recovery profile has them curious anyway.

[cherylannes]

Sorry Michael,

I inverted the numbers when I typed.....

FISH is fine until it gets to zero, then PCR is the only way to track the status of the disease as it is looking at the BCR ABL transcripts (signals).  As for FISH, it looks at 200 dividing or undividing cells....That is why I tend to like FISH...

Your recovery is curious....And still worthy of some sort of celebration - after all we are all still here and healthy - Right!

Cheers!