15 replies to this topic

[BP3]

Hello all,
Been watching this forum for a while, just never posted. I am a 40 yr old male dx in April 2014 with cml. Took hydrea and allopurinol for a bit then went on tasigna. Had low whites for a bit, then they recovered. My platelets then dropped to 11, had an infusion, quit tasigna then they jumped back to 400 or so. Took half dose 150 mg of tasigna again until platelets dropped to 20's. Quit tasigna again(July ) and have not started back. Onc put me on 20mg of sprycel today. Hopeful it will do its magic.
I guess I am just looking to see if anyone else has experienced similar issues with their tki and what their experience was.

[Trey]

The platelets are usually the last blood "cell" issue to normalize during TKI therapy.  Extended periods of low platelets are fairly common.  The drug breaks should help.  Our docs need to realize we can live with fewer platelets than they would like us to have.

[BP3]

Thanks Trey.

[Damerault]

I have had a very similar experience. My PLTs dropped on 100 MG of Sprycel so took a break and they recovered and went on 50 MG Sprycel and the same PLT drop so off Sprycel again. Then after the PLTs recovered went on 300 MG Tasigna twice a day and the PLTs dropped Again! Went off that until they recovered and now on just 300 MG Tasigna. At this point I was referred for a BMT and tested for any abnormalities in my bone marrow that would make me resistant to the TKIs. Luckily that was not the case. The plan then became to stay on Tasigna for 3 months no matter what. I have received multiple PLT transfusions as well as Red Cells and a shot to increase my Granulacytes to help fight infection. After a lowest PLT of 15 I am now back up into the 60s without any transfusions. Hoping to stay on this upward climb. Wishing you good luck.

[BP3]

Thanks damerault. That sounds almost exactly what I am dealing with, just a reversal of meds.

[Damerault]

I'm being treated at a great local hospital and Mass General Hospital in Boston. The idea to push through the low blood counts and not go off the meds seems to be working for me. Next appt next Tuesday and hoping for higher or at least the same counts. If I can stay on the Tasugna and not get a transfusion than it is a good day. I get tested every two weeks. Keep us updated on how you do.

[BP3]

Platelets were up to 64 yesterday. Hopeful they keep climbing!

[Damerault]

Good news!

[BP3]

How did it go damerault? I went today...dropped from 67 to 47. See the doc Tuesday.

[Damerault]

Unfortunately not going well. I am still fighting low PLTs (36) and low red cells HGB 7 two weeks ago required transfusion. My hematologist Onc thinks it might be medication (depacote) I am taking for my headaches. I don't think so as that has been almost three weeks being off and my counts haven't come up. Ironically, the headaches are a side effect of the Tasigna. I wonder how long these low counts will last and if they will let me stay on Tasigna. It is lowering my BCR-ABL which at last test was 2% PCR.

Hope you have had higher numbers.

[Trey]

Tasigna is the main issue, but I would not take Depakote with Tasigna since it can also cause lower platelets by itself.  I would use naproxen.

 

https://www.depakote.com/

 

The body must transition to making good cells after it made leukemic cells for so long.  The platelets, red blood cells, and of course white blood cells are all affected in CML because the leukemic stem cell is above the level where the platelets, RBCs, and WBCs branch off in the blood making process.  So the platelets and RBCs are negatively affected by the CML. 

 

So the Tasigna has a suppressing effect on PLT and RBC, but the main issue is the body recovering from making leukemic cells instead of good cells.  For some this recovery can take a long time, even years.

 

In the meantime you may need to take drug breaks or lower dosage to 300mg once per day.

Edited by Trey, 08 December 2014 - 10:43 AM.

[rcase13]

Can lowering the Tasigna doseage or stopping for short periods cause mutations or resistance?

[BP3]

Still hanging in the 50's here. On 40 mg sprycel. May be put on 60 tomorrow. I used to take depakote for seizures in my teens. Really did not like it much. The only drug I take now is the sprycel. Good luck on your journey.

[Trey]

There is no reason to believe that lowering dosage causes mutations. 

 

Below is a re-posting of information I have provided in the past related to this question:

 

I do not personally believe in the "low dosage resistance" theory, which makes no sense to me.  The leukemic cell mutations generally occur when the leukemia is not well controlled, certainly well above CCyR.  A few years ago the leading Oncs were  expressing concern about dosages below 400mg causing drug resistance.   These same Oncs have softened their statements over time.  The NCCN Guidelines recommend dosages below 400mg for low counts and other severe side effects.  Dr Druker has said he is OK with lower dosages for those with low level disease as long as they maintain a  minimum Gleevec plasma drug level of 500 ng/mL.  Quoting Dr Druker:

"Certainly, I would consider lowering the dose for patients who have had a least a 3-log reduction, have a very low risk of relapse, and maintain this for a couple of years.  I would also consider lowering the dose for people with a complete cytogenetic response who have maintained that for at  least 4 years, when I know their risk of relapse is extremely low, and  for anyone for whom imatinib is affecting the quality of their life.  How would I do this?  First of all, I'd look to see what doses did it take to get them to their response. If they needed 800 mg to get to a complete cytogenetic response, I'm not going to be eager to lower their dose. If we started them on 800mg, and they got a very rapid response,  I  might actually think about lowering them. I would absolutely recommend  monitoring plasma levels and not reducing below a drug level of 500 ng/mL"

http://www.leukemia-...scriptfinal.pdf

So Dr Druker obviously believes that 500ng/ml is "safe".  And some can achieve that on lower levels than others -- some maybe on 300mg, and some on 200mg per day.  This is where "your mileage may vary".  Since 400mg will generally provide most patients with 1000 ng/ml or higher, you can do the math.   But recall, the Gleevec absorption rate differs in each person, so Dr  Druker recommends Gleevec plasma level monitoring for lower dosages.  Dr Shah (in a speech in Canada) said that he was rethinking the issue of whether lower dosages could cause resistance, since it now appears that the basis of resistance is probably there from the beginning stages of the CML and not caused by a lower dosage (paraphrasing).  This is shown by the fact that most drug resistance occurs within the first year or two after diagnosis as the low  level resisting cells grow slowly over time to detectable levels while the non-resistant cells are killed off.  That is why the leading Oncs say that if we make it through 2 - 3 years without  drug resistance, then it will not likely occur after that (but there can be rare exceptions).  [NOTE: I am NOT implying that Dr Druker or Dr Shah would agree with my actual dosage reduction.]

There  is another way to look at this issue logically.  The issue of drug resistance is best shown by antibiotic drugs.  Most of us have taken antibiotics, and we were always sternly warned to take all of the pills in the bottle, even if we feel better.  The reason is that the antibiotics kill bacteria, and and if we only partially kill a bacteria (only take partial antibiotic dosage), then that bacteria may just be "stunned" but then survive and grow stronger and learn how to overcome that drug.  That is why antibiotics must constantly be changed and new ones invented, as bacteria becomes resistant to the older antibiotics.  But Gleevec does not work in tha same  way to kill leukemia cells.  Gleevec will simply latch onto a docking  port that the leukemic cell needs to use to proliferate and survive.  By occupying that docking port, the leukemic cell is shut down.  There is no partial shut down.  It is either turned off or it is not.  So logically it does not appear that typical drug resistance is likely to occur for these TKI drugs.  Additionally, because we cannot take enough drug at first to shut down all leukemic cells, one would assume this  would cause resistance in the cells that only saw "partial" dosages, if  the TKI resistance theory were true.  So the issue of resistance does not really fit the TKI drugs (any of them).  But most docs revert to what they have seen drugs do in the past, so they are cautious about this issue until  proven otherwise.  So it seems that the issue of TKI resistance (which has always been unproven) should not be an over-riding concern in the face of bearing long term side effects.  This should allow Oncs the flexibility to use lower dosages of Gleevec, Sprycel, or Tasigna in patients  where it makes sense.

Another issue is relates to leukemic burden.  At diagnosis most of our WBCs are leukemic and there are about 20 - 30 times more than average.  At PCRU very, very few are leukemic and the total number of WBC cells is normal or often less than normal.  So why would it take the same drug dosage to deal with these various levels?

If a person is PCRU for over two years and can decrease to 300mg or even 200mg Gleevec for the long term (or simliar reductions in Sprycel or Tasigna) why make the patient continue to take full dosage forever and suffer with side effects?

[rcase13]

Trey, thanks for repeating that for us newbies.

[Damerault]

Thanks for the info Trey. I am really surprised at my Neurolgist who knows my medical history put me on Depakote when a known side effect is low platelet counts. I am going to look into the Naproxen. My big concern now is that they won't let me stay on the Tasigna because of these low counts. I have already been reduced to 300 mg once per day. That is what I am taking now.