UK CLL Forum, UKCLLFORUM

Is prognostic testing over rated?

Topic Made On: Jul 14, 2011 03:18pm
Nick

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A recent commentary piece by Dr. John Gribben a leading CLL researcher now at Barts in London, discusses the value of prognostic tests in CLL. An important read for UK patients perhaps. As invariably we use US facilities to access information and support, necessary for us to progress, we also can pick up misleading trends as fact or normal. Perhaps one that can affect us greatly is the patient culture of prognostic testing over there. When the reality is that here it is not available to us pre treatment and is considered unnecessary, This then can leave us believing we are being failed by the system, Apparently not so, Dr Gribbens article goes along way to explain the thinking behind this. This may help us not be distracted by medical systems that are not relevant to us and could help us come to terms with our disease sooner?

In his article he poses the following questions:

"Is there any benefit in assessing prognostic factors in CLL patients at presentation?



"Which prognostic factors need to be determined at the time treatment is required?"



"Do these prognostic features alter our approach to therapy?"


The article is written in a conversational format so is not hard to understand.
You must be a member of the Cancernetwork to read these papers but it is free to join...

Dr. John Gribben's article:
http://www.cancernetwork.com/leukemia-lymphoma/content/article/10165/1899632






Replied On: Jul 15, 2011 05:09pm
pastongriffin

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Like many other CLL patients, I have not had all the prognostic tests - but those I had appeared favourable. 13q,Stage A, but the cancer progressed quickly, doubled lymphocytes in 6 months and B symptoms and I ended up needing treatment within a year. It turned out my bone marrow was 70% infiltrated with a diffuse pattern. My haematologist says the only sure way to know what is going on is bone marrow test from this time forward...not good news, I hate them!



Replied On: Jul 16, 2011 02:07pm
Nick

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I am beginning to understand that everything can prove an exceptption to the rule. Even the mutated unmutated status of HvIg, although this seems to give the best indication of how the disease may progress, even this doesn't follow rules, as we now know that the particular family of genes in use can be the trump card good or bad. So you can be unmutated and indolent or mutated and more progressive, Instead of the more normal pattern. The Hv family of genes can also trump your kareotype status thinking, for this can cause some 17's to be indolent and some 13's to be more progressive too. Many are still not understood.

I found out my kareotype as tri 12 which is labelled as an intermediate type, and probably unmutated as the majority are, but is of little conclusive value as a prognostic result, my bone marrow is /was 45% infiltrated.

A year down the line, monitering my wbc alc and tissue involvement/nodes/spleen/liver are the only signs/Indicators available and I have faith in this process. When adding this to the doubling time at the time, I think sufficient evidence would be available to tell me when treatment or further investigation may be necessary. Perhaps when thinking of the skills required by CLL medics I now consider the application of their knowledge as an "art", criticle for us to be treated correctly. I am very pleased to be under the care of some one with this knoeledge. The disease is going to do what it's going to do. We just need to know we can enjoy life and if or when treatment comes we feel we are in safe hands??

I agree a BMB is not a pleasant mental experiance, but the procedure is very straight forward and pain free, if not a little uncomfortable, I intend only to have another at treatment or during/following when assesment is necessary,



Replied On: Jul 16, 2011 04:52pm
Nick

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Professor Hamblin has just posted his opinion and take on "Who should have prognostic markers done and when?" He has split the patient group into four categories . I don't know how we NHS patients in the UK can apply his suggestions in practise as prognostic testing pre treatment is not available outside of trials and much information is withheld from us? How much is available to us at treatment and what is standard testing protocol at treatment? He does suggest for some, much understanding is needed but as more knowledge accumulates it may become more useful.

http://mutated-unmuated.blogspot.com/2011/07/who-should-have-prognostic-markers-done.html

Terry Hamblins article is thought provoking and does also include both patient view points pre treatment.I guess I fall into the category of; If want it, can't get it but, don't need it regardless. For without further information answers can not be given as I am tri 12? Perhaps a good enough reason for me to continue pushing for testing, or join the CLEAR trial (if eligible)? If not for me , for others down the line.

Excerpt
"At the moment there is no need to test for trisomy 12 or del 13q, but if these are available in a cheap package you may as well since I do believe that as more knowledge accumulates they will be useful. With del 13q it is likely to be the size of the deletion that is important. It is always better to get the markers done at research labs rather than at commercial labs, because they often obtain more information than you pay for and as time passes that information becomes useful. I am still waiting to see what becomes of the information that those with trisomy 12 often have trisomy 16 and sometimes 18 or 19 as well. They may all belong to a single stereotype.


On this topic following these comments and opinions on a US site, Chris Dwyer a Canadian patient advocate and researcher who has been instrumental in a lot of my learning commented:
"While these test are fairly common in large research hospitals in the U.S. the fact is that they are simply not available for patients in other countries...this is true of IGHV outside of clinical trials."

"Clinically, the only one that matters is the FISH markers for patients that have aggressive CLL, to separate out 17p deleted patients..."

"IGHV is probabaly more important as a Quality of Life matter... "



The CLL Canada website At:
http://cllcanada.ca is a more technical and detailed patient site containing much current published information, put together perhaps with an eye on a system a lot closer to our own than the American. It is a very useful research tool and chris has become a friend.




Replied On: Jul 18, 2011 11:08pm
pendle witch

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I feel as though I am trying to wade in on your discussion, without really knowing what you are talking about. I was diagnosed a year ago and all I have been told is my white blood cell count,so sorry I don't understand the other prognostic indicators you mention. This may be something you know about already, but there was a trial published on the web a few months ago, directly relating CLL to poor digestion, which resulted in the immune system sending the wrong signals. Stupidly I didn't favourite/bookmark it (don't want to upset my husband), but at the risk of sounding naive, it's probably worth getting an allergy test uk, check up. I found I was very low in the probioics needed for digestion, together with zinc (needed for immune system). Check out their website for nearest practitioner: allergytest4you.co.uk. It was a real eye opener - I feel tons better and everyone keeps commenting on how well I look, plus lost around 1 st in weight. It isn't hugely expensive, around £70.



Replied On: Jul 19, 2011 11:46am
Nick

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Hi pendle witch, Some times I wonder if I know what I talk about!! LOL
The gist of my thread was explaining that combined with the Binet monitoring scale our physical symptons and doubling time, is all the majority of us in the UK have to go on, and how much of the rest is important to us anyway? I posted on the same thread that I joined on a US site below, following Chaya's review. She has a very colourfull and understandable way of presenting the facts and her opinions. But American and perhaps relates more to them than it does to us?
--------------------------------------------------------------------------------------------------------- Chaya has published her take, interpretation and opinion on Dr John Gribbens comentary and included Professor Hamblin's in her review.

http://updates.clltopics.org/3695-prognostic-indicators-who-when-what-and-why

on prognostic testing pretreatment I believe I fell into her A category, those who wish to learn and if not influence, be an informed party involved in the treatment decisions necessary as my disease develops. Her writing has at times been what enabled me to understand in detail, knowledge about the disease and the meaning behind the evidence. But then I hit the personal barrier I could not implement what I had learnt as I am within a totally different health care system and do not have the flexibility to maneuver, that you guys do. Chaya briefly explains how foreigners who's expectations have been lifted by knowledge of new prognostic testing capabilities will suffer when these can't be carried out at home. I pasted below an exerptt that really does not help me. But I hope makes you all realise what opportunities you still have and can find out enough to make some short term decisions at diagnosis.

excerpt

"I can think of a bunch of “life” decisions patients may need to make, depending on their long term CLL prognosis. Do you change jobs, possibly risking healthcare coverage or the quality of the coverage? Do you take on additional debt and move to a more expensive house, based on the assumption that your healthy paycheck is going to be around for a long time to protect your family? Would you slow down, take the time to smell the roses and spend more quality time with your family, if you knew you were in the more aggressive unmutated IgVH risk bucket? Would you make different therapy choices, perhaps line up your ducks for an eventual stem cell transplant – sooner rather than later? Would you continue to indulge in behavior such as smoking and excessive sun exposure, if you knew high risk CLL also means higher risk of secondary cancers? I can think dozens more such questions. But here is the problem: would healthcare providers consider such one-of-a-kind personal issues, if the slam dunk expert opinion is that detailed prognostic testing is only to be done in the context of clinical trials?

"CLL is a complicated disease. With the exception of a percentage of patients who luck out and have very indolent disease, majority of patients will find their CLL diagnosis comes with the guarantee that it will dominate big chunks of their lives. You will need room to maneuver, take care of personal and family issues that are not part of any standard healthcare providers’ do and don’t lists. The choice should be yours, the decisions should be made based on what you want and need."

Unfortunately many in the UK seem to be lumped into the same bucket at diagnosis, we are told you may be the lucky one but know also maybe not. So to be safe have to take everything on board prudently, including the worry that comes with the wait. But can get some on the shopping list, just not the genetics.If you are someone who feels they need to know, not knowing enough is an assault on your quality of life. I found out my Kareotype due to physical concerns and in my case that is enough. But I remember being trapped in limbo before! if you need to get them you can find providers who will for a fee.
Did getting some answers help me? I don't know as inevitabley so much time had passed, perhaps I had come to terms with diagnosis and physical changes had caused me to take stock of my plans anyway. There is the question if you were to find you were 17p deleted did you really need the news? knowing I have an intermediate type, made me realise it is real and I know now I am not in the indolent bucket, but then I think I knew that already.

Nick




Replied On: Apr 18, 2012 09:59am
lisagalton

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Hi there
I have 11q deletion and after 3 years am still not sure what it really means to me - can anybody clarify?



Replied On: Apr 20, 2012 01:23am
Nick

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Hi Lisa.

If I am honest I think it is a changing picture for me now, medicine moves on i know now FISH testing is being encouraged now as part of the diagnostic work up, to identify specific mutations such as p53, although there is considerable regional variation. Time does give us some of the picture on its own. I don’t need or wish to know as much and I realise how insignificant what I knew was. ( :

You mention it has been three years have you required treatment? I hope you have been able to learn some, if not my response may be gobledy gook. (it is late) If it is I will signpost you to something a little easier to read.

Reading back on previous posts I realise how much more I have been able understand by reading and asking my consultant questions. Also how more of the picture is beginning to unfold with new discovery. Mutational status and which family of VH genes is in use are very important.

But Yes It is puzzling, improved testing is identifying small mutations that may have significant prognostic value in indicating subtypes. From what I remember Single allele deletion responds well to the standard first line treatment approach if you are fit enough to qualify whereas double allele deletion is harder to treat and has a poorer prognosis. The recent identification of ATM mutations that can be independent of allele deletion suggest a group with different prognosis and responses to treatments and a more aggressive pathway.

In my own kareotype +12 the intermediate type apparently was of neutral prognostic value, but the recent identification of the significance of NOTCH1 Mutations as independent prognostic indicators suggests a portion of +12s should be reclassified as more aggressive.

Improved and developing testing capability has led to Identification of some of the variants, which we hope will come together in the future with more targeted treatment. I thought I knew what the significance of being +12 was !

I think I have concluded that one marker cannot determine or indicate outcome. There are too many variables and influences in a diseases course, not least the potential intervention with novel treatments in the future, too many possibilities. Perhaps others can offer their clarification.

I hope some of this may help

Nick

http://www.cllsupport.org.uk/prognostic.htm

ATM and chronic lymphocytic leukemia: mutations, and not only deletions, matter
http://www.haematologica.org/content/97/1/5.full




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