BCR result

Hi Wal

I'm not an expert on this, but from what I can see it looks like you're in great shape.  From everything I've read, it seems as though drugs like nilotinib work very fast at the beginning and then slow down as time goes by.  This makes sense - there were many leukaemic blood cells to target when you first started treatment, and now there are very low levels of disease left in your blood, so the drug has a harder time eradicating the cancerous cells.

I will make a farming analogy to explain the point.  Let's say you're in a field of corn that is being attacked by hordes and hordes of locusts, and you have pesticide in your hand.  At the beginning, when every sheaf of corn is covered in locusts, it will be very easy to eradicate large groups of them at once, as you would just spray everywhere and be virtually assured of hitting a locust.  However, some of the locusts will survive this attack and, if you allow them to breed, they will return in full force.  This is why you would keep searching for them by entering the cornfield every day with your pesticide, spraying any locust you see.  This is much harder than before because there are so few of them left, and you might spend days without killing one.

I think it's the same with the nilotinib.  At the beginning of treatment, the leukaemia cells are everywhere, and the drug isn't short on targets.  However, when there are as few as 18 in a thousand left, it is very difficult to find and eradicate those "hidden" cells.

Also, in terms of response times, you're doing GREAT (much better than me!).  You are way ahead of the goal of being below 1% at 6 months and you have a further 6 months to eradicate those pesky remaining cells!  You will definitely get lower, but it will in all likelihood take longer to get rid of the last few.  Anyway, your BCR-Abl has almost halved since your last test, and that is wonderful.

For comparison, here are my results:

Diagnosis 72%

3 months  2.7%

6 months 1.6%

9 months 0.57%

12 months 0.36%

15 months 0.27%

18 months 0.16%

So as you can see, my response is nowhere near as good or as fast as yours - I'm on dasatinib and my doctor is satisfied with my progress.  

I hope this gives you some confidence in your own response!

Best wishes from South Africa

Martin

Hello there,

I agree with everyone's responses to your post up to now that your result is indeed very good news.

My diagnosis was a month and half prior to yours and i'm also on nilotinib 300mg twice daily. My 3month was 0.9% and after having started on interferon weekly as adjuvant therapy i was able to get my figure down to 0.08% at 6month time point. But i've now stopped interferon and back to monotherapy with just nilotinib due to a transient thyrotoxicosis.

Anyhow, i just wanted to add a separate perspective for consideration on top of MartinZA's already great explanation on why small residue of leukemia cells persist in high number of CML cases requiring lifelong TKI therapy. To elaborate on that briefly; one of the intended mechanism of actions of a TKI is to block off the BCR-ABL tyrosine kinase's activity critical to the survival of Ph+ leukemia cells in order to kill them. Unfortunately, this "seek-&-destroy" mechanism of the current available TKIs (nilotinib included) only binds to and kills off differentiated leukemia cells but spares the leukemia stem cells (LSCs), because these abhorrent hybrids are self-renewal and do not depend on the tyrosine kinase's activity of BCR-ABL1 to strive relative to their biogical (and histological) stability, differentiation and proliferation. As a direct result, these independent LSCs continue to survive, replicate and differentiate indefinitely into leukemia cells in CML. Therefore, there will always be a traceable reservoir of leukemia cells that persist which possibly triger the acquired resistance in refractory disease relapses in the absence and/or prolonged disruption of a TKI treatment which in turn may promote progression to the terminal stage in this otherwise manageable chronic disease.

Now, back to your result, to me it shows nothing short of an optimal response to your TKI therapy according to the ELN's current treatment management and assessment guidelines for CML.

So, i wish you the best of health in your journey with CML.

Best Regards,
Ellie.

Dear all, First of all thanks a lot for your explanations; it cools me a bit down. Bit i read the more it goes down at the beginning of the treatment the higher is the likelyhood to stopp treatment at all after a some years.possibly Interferon in addition would be helpful. Does anyone has experiance with Interferon as an addition? I would be very happy if someone could share his knowledge. Best regards

Dear Ellie, thanks a lot again. I know there are some clinical trails which combines nilotinib and interferon. And from what I read (also your development) there are indications whereby a combination leads to better results. I am seeking for further information/experiance on this. From what I understsnd so far pushing down the bcr level is most crucial in respect of this illness and increases the chance to stop drugs at a later stage. Best Regards