2 replies to this topic

[DebDoodah22]

My test results had been climbing slowly over 9 months for some reason, despite pretty good compliance (missing only 1 or 2 doses) ...then in April I had a series of bronchial and sinus infections that would not clear up. I was running low fevers and dealing with chronic coughing for about 6 weeks. During this time, I was feeling awful, despite the antibiotics and I messed up royally on my sprycel missing about 11 pills over the period. I did not intend to miss and frankly I was a bit shocked by how many I actually missed when it was time to reorder meds. I was really worried when I went for my blood draw that I was going to lose response or see the numbers continue to climb and then this report with a steep decline! Can this be real? I am on 80 mg Sprycel, diagnosed in Nov 2013. Can your numbers dip like this or is this not a big deal, because it feels big to me even though I am still operating in the foggy headed fatigue zone. Is this good or a fluke?  image.jpeg   57.95KB   2 downloads

[scuba]

Deb - You're doing great! There is a very high likelihood that you don't need 80mg Sprycel to maintain excellent response. You are responding very well to Sprycel. You should talk to your doctor about cutting your dose to 40mg and see how things go month to month. I would not be surprised if your PCR continues to drop.

[Trey]

It is not as though TKI drugs work each day to kill off leukemic cells which popped up on that same day.  Because leukemic cells take several weeks to develop fully, the TKI can stop them at any point along the way (except generally at origin due to alternate stem cell survival pathways).  So occasionally missing your TKI pills here and there is not as critical an issue as it might seem.  If you don't get the leukemic cells on any given day, there is always the next day.  But you don't want to miss several days in a row unless a drug break is required.

 

However, there can be a delayed effect where the missed dosage had an effect later rather than sooner.  That is because the blood cell development is in the marrow, while the PCR is usually done on the blood.  It can take a couple weeks for marrow cells to develop fully and go out into the blood.  So a PCR within a couple/few weeks of the missed dosages may not show the full impact.  Secondly, for some of the tougher leukemic cells (higher order progenitors) it might take a higher concentration of TKI inside the cell, and that could rely on a build-up over several days.  This is because the leukemic cells do not have just one BCR-ABL signal mRNA inside them (even though there is usually only one Philadelphia Chromosome per cell), but cells usually have multiple messenger BCR-ABL mRNA per cell.  And each one must be inhibited to make it self-destruct.  Also, some patients just need more drug in their plasma in order to overcome specific issues with drug uptake into the leukemic cells, so missing occasional dosage can have a greater impact for them. 

 

But most patients can miss several days per month without an effect on their drug response.  But it is best not to have those missed days occur all in a row, because that becomes a problem of allowing the cells to divide in an unhindered manner.  Also, many patients could take less drug daily, and the excess dosage is generally wasted.  We are not all the same.