Prognostic markers and the future. Genetic testing.

[Kwenda]

We have only just scratched the surface with our tests for 13q, 11q 12 tris and 17p.

The real world is a lot more complicated. However the costs for such detailed testing continue to fall and thus there becomes hope for real knowledge of how CLL develops, is then tested and thus treated.

For additional information see Dr Sharman’s Blog of Sunday February 24 2013. Prognosis Markers Defined.. cll-nhl.com/

DM W & W 13q

[Cllcanada Top Poster CURE Hero]

Here is an example of a U.S. company doing advanced CLL testing. However, clinical, other than 17 p these tests won't mean much until there are new sub clone targeted therapies...

There are other companies doing these as well, this is an example

not a promotion for this particular company...

CLL CompleteSM includes cytogenetics, immunohistochemistry,

and molecular diagnostics methodologies. The tests included are:

MatBA®-CLL Array CGH

IGHV Mutation Analysis

NOTCH1 Mutation Analysis

SF3B1 Mutation Analysis

TP53 Mutation Analysis

FISH: TP53, ATM, D13S319, c-MYB, chr.12, CCND1/IGH

Karyotyping

CD38

ZAP-70

Blood or Bone Marrow...

cgimatba.com/matba-for-cllsll/

[Quarry]

Thanks Kwenda. Dr Sharmans's blog is good and, what is even better, understandable.

However, I don't know what CLL marker I have! I was only diagnosed 3 months ago, but was naively expecting to be told at last meeting with consultant which marker I had. I could thus walk away with some greater certainty about what might happen into the future.

However the response was firstly, any test would be inconclusive (as I don't have enough bad cells) and secondly, that just because I have one marker today does not mean others won't appear. Thus, for instance, knowledge that I have a reletively harmless variety today does not mean one of the really bad ones will appear tomorrow.

I don't doubt any of this.

So I am now assuming knowledge of a marker is really only to guide any treatment you need at that time (if you need treatment). Knowledge of your current marker It is not a reliable indicator as to what might happen in future, beyond indicating prognosis assuming your current marker continues alone.

So it is not a simple one-marker-to-overall-prognosis realtionship.

What do others understand?!

Andy

[Kwenda in reply to Quarry]

I think this will all depend upon the degree of progression of the CLL..

If you have only just been diagnosed and the ALC, Absolute White Count is only a small amount above normal, then perhaps waiting a while is best. The labs do need a reasonable sample and anyway your progression could be very very slow. ( Hopefully.! )

But if the ALC is significantly above normal then the mutated / unmutated testing should be done as this is a good indicator and mostly does not change.

It is true that clonal evolution does often occur and that a person might start with 13q del and then progress to 11q or 12 tris. ( See CLLTopics for more on this )

It has also been recently proven that chemotherapy does cause some clonal evolution, so waiting until treatment become absolutely necessary is also a good plan.

The BEST plan is to hold on until the new drugs such as ibrutinib become readily available. They are undergoing trials, and the results are spectacularly good.

[Quarry in reply to Kwenda]

Thanks Kwenda. My White Cell count is indeed only marginally above normal, though lymphocytes outnumber neutophils by more than 2:1. My consultant not worried about that though (not quite what CLL Support Association site blood-results-guide says, but I totally trust consultant). I am hoping for a v v long W&W ...indeed I will need a v long time to understand CLL, as it is obviously not a simple disease!

I might well be being dense, but where is the CLLTopics you refer to?

Thanks

Andy

[Kwenda in reply to Quarry]

Hi,

CLLtopics is quite a good website. clltopics.org/index.php.

For clonal evolution go to :- clltopics.org/DC/ClonalEvol...

And also :- clltopics.org/Alert/direct_...

Also see :- cllcanada.ca/2010/pdfs/arra...

And also :- cllcanada.ca/2010/pdfs/adve...

That is more than enough reading for one day..!!

Take the time to slowly read and follow the various websites, so that you are up to date and can then talk knowledgeably with your oncologist / haematologist.

As Andrew Schorr of Patient Power says ‘knowledge can be the best medicine of all.’.

Dick

[Cllcanada Top Poster CURE Hero]

Each of the old basic markers like 13q, 11q, Tri12, 17p, have both indolent and more aggressive sub clones. For example 13q generally is indolent, but if the size of the deletion is large and RB1 gene is damaged, then 13q gets more aggressive, Similarly, Tri12 is moderately aggressive, however if the NOTCH1 gene is mutated, Tri12 start to approach 17p. with TP53 mutation, the most aggressive.

So, while the FISH tests may give you basic marker, it doesn't really say very much about an individual patient's prognosis.

New tests are round the corner and we will have a far more accurate picture of CLL in the future.

~chris