Change in 13q deletion?

[hhk50]

I recently had a BMB performed, the first since I started Ibrutinib four years ago. I noticed that my 13q del has dropped from 21.2% in 2018 down to 0.4% today. Why would this be? A result of the Ibrutinib therapy? I didn't think that therapy would change the chromosomal structure.

[AussieNeil Partner Administrator]

You haven't provided enough information to provide suggestions. Knowing your lymphocyte counts now and when you first had your FISH tests done would help. It may be that ibrutinib has wiped out nearly all your CLL, so your FISH test is mainly measuring healthy B cells, or perhaps a new clone without 13q del has become dominant. The latter would be unlikely.

Neil

[hhk50 in reply to AussieNeil]

Thanks, Neil. ALC in 2018 was 82.6; today it is 1.90

[AussieNeil Partner Administrator in reply to hhk50]

Most of those lymphocytes remaining now would be T and NK cells. You should have very few B/CLL cells.

[hhk50 in reply to AussieNeil]

Thanks very much, Neil.

[country76 in reply to AussieNeil]

Does that mean he possibly can go into remission with Ibrutinib?

[AussieNeil Partner Administrator in reply to country76]

It's entirely possible to reach uMRD on ibrutinib and enjoy a remission with a treatment holiday. 10% of the participants in an early ibrutinib trial achieved uMRD after 4 years on the trial and 13q del is the most advantageous prognostic CLL marker.

We are still learning which markers are the best predictors of what will happen long term on BTKi drugs like ibrutinib. Some experience tumour flare after they stop taking their BTKi, which is reversed by restarting on it.

hhk50 , you might like to discuss this with your specialist or perhaps a dose reduction if you are experiencing side effects you'd rather not have. Most specialists prefer patients stay on their BTKi for as long as it keeps working, however.

Neil

[hhk50 in reply to AussieNeil]

At the age of 72, my wife and I still have a goal of a long-term overseas mission assignment. This has been impossible due to the Ibrutinib leash that keeps us in the United States. But, perhaps, with an Ibrutinib holiday? Definitely at the top of my list to talk to my specialist about. And, it's all in God's hands.

[SofiaDeo]

My understanding is that the FISH percentages refer to the number of cells in a sample overall showing abnormalities. So if before treatment, X percent of cells are defective, after successful treatment killing off defective cells, one would expect the percentage of cells overall with defects to decrease. It's not "X percent of the DNA" in every cell is defective.

originalText

I have a complex karyotype CLL including a 17p deletion, but that percentage of cells is very low, and only one DNA allele is affected. So I do have some functionality/ability to produce the apoptosis proteins that the 17p region codes for. I just don't have the normal amount, since one allele is deleted. The other mutations are the predominant ones, and my 13q deletion is biallelic, meaning both the DNA strands are affected. Those cells have zero ability to produce the proteins the 13q region codes for. Since CLL cells do eventually die, I theorize one reason I am still around/responding to treatments, is that the bulk of my CLL disease are cells sensitive to therapy. IMO the amount of cells with the 17p deletion are low enough that they eventually die before they grow enough to impact other organ systems. And my 13q deletion, which is the predominant one at 77% of cells affected, seems to be calling the shots as to whether treatments are working or not.

So my theory is it's not simply the fact of whether or not one has a specific deletion, other things also come into play. Is it a single strand mutation or both DNA strands, the percentage of those defective cells, and probably other things that scientists have yet to discover since things are inter related throughout our body systems. With CLL being a rare cancer, we are not likely to find out exactly how these variables affect our disease state for a while yet. A larger number of patients will need to be assessed and studied, and data compiled. That takes longer with a rare cancer.

[bennevisplace in reply to SofiaDeo]

Hmm, could this be a case for OGM? healthunlocked.com/cllsuppo...

[SofiaDeo in reply to bennevisplace]

I think so!

[Big_Dee]

Hello hhh50

Not surprised, your percentage of deletion will raise as you go through W&W, then drop after treatment started. I have had 4 FISH tests. 13q deletion increased at each test before treatment, then went to 13q normal after treatment with B+R. Latest FISH shows greatly increased deletion percentage as I am now relapsed and awaiting treatment. Blessings.

[hhk50 in reply to Big_Dee]

Thanks, Dee.

[Analeese]

When diagnosed my fish test showed deletion of 11Q and also trisomy 12. After treatment my fish test showed negative for all chromosome changes.