10 replies to this topic

[johnny99]

Hi fellow CMLers! I stumbled upon this site yesterday and so glad I did! I have spent the whole day reading threads, and I have a question of my own I could use some help with:

I was diagnosed 6 months ago, CP, and have been on dasatinib on and off ever since due to low platelets. Achieved CHR quickly, but at 3 months I had minimal cytogenetic response and no drop in PCR. Will have BMB again in a couple of weeks but not very hopeful as I have been off dasatinib about half the time and if all goes well only 3 weeks on it at 50mg immediately before the BMB. (I'll save the interruptions/dosing issue for another discussion) At diagnosis and also at 3 months about 1/3 of the Ph+ stem cells were also -Y  (missing Y chromosome). I have been told this can happen in older men, but I am only 27! My onc is worried this may be the reason for the myelosuppression, as maybe my "normal" stem cells are also -Y (no evidence of this yet) and slow to repopulate, and thus a BMT would be necessary. I speculate that since I was diagnosed fairly late (300 WBC, spleen huge) it could just be plain garden variety myelosuppression, which is bad enough I guess. According to articles I've read, the jury is out on significance of -Y, but not a good sign for sure. I am interested if anyone has any knowledge or even first hand experience of -Y and its impact on low counts/slow response?

Thanks!

John

[Tedsey]

Try not to stress out about the PCR.  It is only useful after a Complete Cytogenic Response (or zero Ph+ cells).  I have not heard of -Y chromosomes having to do with CML or myelosuppression, (just long ago, before TKIs, it may have predicted greater longevity in adults dx with CML).  I am sure some others will chime in with their knowledge.  Reaching CCyR at 6 months would be very quick.  CCyR is expected 1 year to 18 mos. after TKI therapy.  I think you are not making greater progress because you have had too many drug breaks for the TKI be more effective.  Let me know what your PLTs are and what they have been like for the last 6 months.  I have dealt with this issue for a while now.  I can tell you what my treatment plan was.

If you were dx in the CP, having a large spleen and 300K WBC probably doesn't have much meaning when it comes to optimal, partial, or bad response to TKIs.  The most important thing is that you have 0 Ph+ cells after 1 year to 18 months, and the BCR-ABL protein stays low.  The hardest part about this disease is mental, thus, the time it takes to see how your particular CML story plays out.  And no one, not even hems or oncs, can predict the future (although some may like to try, but most of them can only tell you confidently what the drug companies have published).  In this day and time, despite some possible bumps in the road, most people will likely outlive the CML in their bodies.  Glad you found us.  It will always be in your best interest to be one of the most knowledgeable persons in the room about CML.

Please take care.  Hope your journey to healing is smooth.

Tedsey

P.S.  Try not to freak out about myelosuppression.  I have been low and even lower for 4 years now and have been relatively healthy (it may be luck, but probably my immune system is still doing its job).  I hope your doctor is not shouting fire and scaring you.  You can always contact me.

[Trey]

So you are a 45,X instead of a 46 XY.  Interesting, but don't worry, your non-blood cells are still solidly male (46,XY), so no worries on not being male any more.  Just a little cytogenetic humor to warm things up. 

Anyway, the -Y is not necessarily a bad thing, especially if it is only in the leukemic Ph+ cells.  They need to die anyway.  I would be more "concerned" if they were also in the Ph- blood cells.  The BMB should have pointed that out if it were true, so I assume it is not. 

You may have read about -Y in some older articles, but remember that Gleevec was approved in 2001, so articles older than maybe 2005 are useless since they dealt with patients who were on Interferon and ARA-C crap.  So ignore anything that old.  In the TKI drug era these things are not so relevant, but then I would be fooling you if I implied that everything is known about such issues.  But the chances of success for you on TKI drugs is still high.  The Ph+ cells will likely be killed by the TKI drugs, and the normal blood cells will likely be 46,XY.  So overall the chances are good that all will be well.

You do not say what your WBC and ANC counts are.  Some Oncs get overly concerned and stop TKI drugs too soon.  Most of us have low counts, so it is a matter of degree.  To some degree, if your WBC is low then the TKI is working, regardless of the PCR.  It may take some time for things to level out.  Overall I would tend to default to accepting more myelosuppression while taking more drug than vice versa. 

An interesting side note is that -Y leukemic cells seem to resist transition to latter stages of leukemia.  They actually tend to be more stable.  Odd, but apparently true.  So even that is on your side.  Again, not a lot of evidence, but enough to be relevant.

http://www.unboundme...leukemia__CML__

Please do not read articles about overall body cells being 45,X citing "mixed gonadal dysgenesis" and other things.  I repeat that your overall body is solidly 46,XY and therefore solidly male.  It is only the leukemic blood cells which are hermaphroditic (just a little cytogenetic humor to end with).

Welcome. 

[johnny99]

Thanks for the info Trey! So I will not be buying a purse and some heels just yet

Some Oncs get overly concerned and stop TKI drugs too soon. --> I think this is the case!

[johnny99]

Thanks for the encouragement Tedsey! You're right, the hardest part is mental. My myelosuppression story nothing like the ordeal you had with transfusions and stim shots, nonetheless it was not quite the start I was hoping for. After all, its a complication that most people don't have, so you get this nagging 'things are not going well' feeling. I took some comfort in reading how you and others got through this problem. Here's my story in case someone might find it useful:

week 1: Started on 100mg dasatinib, CHR in a couple of weeks

week 4: PLT drop to 30, pause in dasatinib, they stay around 20

week 7: PLT up to 80, restarted on 100mg

week 8: PLT 150

week 10: PLT 75

week 11-12: PLT around 50-60 (plateau?)

week 13: PLT dips slightly below 50, paused dastinib, PLT stays around 50

week 16: PLT 90, restarted on 70mg

week 17-19: PLT 80-->60-->40, pasued again!

week 20-21: PLT 55-->65

week 22: PLT 90, restart at 50mg

week 23: PLT 90 .... (that's where I'm now)

 

During all this time ANC held its own, lowest was 0.9 during 2nd break. So as I said, not an extreme case, but still bad enough to cause disruption to smooth treatment. The BMB at 3 months showed marrow was hypocellular, so I think it's a matter of the marrow not having recovered yet combined with dasatinib suppressing production. Also my onc is very cautious, if it were up to me I would just plough through, stopping only to avoid a transfusion. I guess now I just have to wait and see how things play out at 50mg.

Thanks again!

[hannibellemo]

johnny99,

If it helps, there are a few of us on here who are taking less than 100mg. of Sprycel and we're doing fine. Interestingly, (to me anyway), Gleevec caused my CBC counts to tank but Sprycel didn't. Then I had to stop Gleevec because of liver toxicity. We all react differently!

I had to lower my Sprycel dosage due to a pleural effusion. I've been on 50mg. for about 18 months now and finally got back to MMR after 15 months at the lower dose. Hope this encourages you to convince your onc to stay the course for a bit longer!

My WBC and RBC have, until recently, always been below normal. Now they tend to fall into low normal or slightly below normal. So I guess I'm as "normal" as I'm ever going to be! There are those who would say that isn't saying much!

Pat

[Tedsey]

Thanks for sharing your numbers, and I see you do your homework!  I tended to post a lot during my ordeals.  It made me feel better to get it all out.  You can sure feel alone when things go, what appears to be, "haywire".  I guess it is all in the course of healing, (but I didn't know that then).  Anyway, you could ask your onc to email Dr. Druker at OSU to see what he thinks about your case.  That is what my 1st onc did.  That is also why I stayed the course with the medication "due or die" (per Dr Druker's advice).  Moreover, I think that may be why I am bcr-abl negative for the 2nd PCR in a row now (but I also understand having a negative PCR has a bit of luck in it and is probably just as good as MMR as deep responses go).  Obviously, it is extremely important to stay on the medication when things start to smooth out.  In the last almost 4 years, I only missed one night because of the stomach flu (threw it up).  I so desperately want to live, I even took it when I knew I wouldn't be able to keep it down. 

Oh, the full blood transfusions I had were only because my hemoglobin was so low (and I couldn't breathe).  I had severe anemia after 6 months on Gleevec.  So, if your HGB is close to normal, there prob. won't be any blood transfusions in your future.  As for a PLT transfusions, (which is avail. too), it will likely only happen if you have signs of bleeding (gums, nose, cuts won't heal, bruising, red blood in stool, tarry, black stools, etc.).  Some people do fine around 20K (but not below).  Most people won't have trouble clotting above 20.  But, everyone is different.  Eventually, my low PLT increased to 90 in the last 4 years (so if your onc takes you off at 90, that's nuts).  This is presently my new normal.  Oh, and the shots I had were for the rest of my low white blood cells and there was one for red.  I hope you will never have to go near any of that. 

Hope you can stay on the Sprycel this time and then kick the CML down to low levels at lightening speed.

Take care,

Tedsey

[Tedsey]

Sorry I overlooked this.  Looks like your onc feels comfort at 90.  In the past, I stayed the course on 100mg dasatinib as low as 22.  Until recently, I had flux from 22 to 70.  But I know some people are more sensitive to dastinib and still do well at lower doses (but they usually started out with higher).  As I think it is still the common thought, it is best to treat the disease with as strong a dose as possible in the beginning.  The idea is to wipe out as many of the lower level leukemic cells (which appears to be what is going on in your case already), so the drug has a chance to get at the higher level leukemic cells that will be left (more or less, the parents of the lower level cells).  "Progress" will seem to go much slower at that point in your treatment.

[johnny99]

I would prefer a more aggressive approach than the present -- within reason... I'll see what I can do about it. I doubt I would go below 20, but hard to say anything for certain as longest continuous interval was 6 weeks on 100mg. BTW just curious, in case this is where I'll end up, what do you mean by flux from 22 to 70 ? That they would go back and forth between 22 and 70 without a clear trend?

[Tedsey]

Sorry I wasn't clear.  The counts fluctuated from 22-70, (ex. 22, 41, 70, 37, etc.), for a couple of years (I just checked the graph).  Crazy, huh?  I am not sure what an average fluctuation is, but I know all blood counts fluctuate, (for example, what they are in the morning may be different from the evening or day to day).

[Trey]

The platelets in the CBC do not tell the whole story.  The spleen sequesters (holds on to) platelets until they are needed.  So as long as the spleen has enough platelets in reserve you should be fine at your levels, which is likely.  The CBC does not know how many platelets are in the spleen since the spleen is very secretive about the cards it is holding.  (So don't play poker with your spleen -- you cannot tell when it is bluffing). 

I have a suspicion that after the spleen has been greatly enlarged by the CML and then the WBC is brought down to normal levels, the spleen may sequester extra platelets since it is still enlarged but does not have many other blood cells to hold on to.  So it may sequester extra platelets for a while to fill the void.  Just a theory.