Genetic Testing Questions

[kathypawpaw]

Is it possible to have CLL if you have no genetic abnormalities?

[AussieNeil Partner Administrator]

No ... and ... Yes!

No, because there has to be some genetic damage for a CLL cell to disobey an order to die (and hence become a tumour of ineffective clones and Yes because there are so many genetic abnormalities that can cause CLL that the standard FISH probe set (and even some much more comprehensive genetic testing) does not detect them all. That's why many of us receive a very puzzling FISH report that states "Normal Karyotype". That's just misleading shorthand for "Whatever is causing your CLL wasn't among the limited number of checks we could perform with the FISH testing you had."

Neil

[kathypawpaw in reply to AussieNeil]

Thanks Neil,

Great answer. I understand what you are saying because it is so well explained. This CLL thing is a very varied disease indeed. Puzzling disease too isn't it? I was happy for the news but now I see it may not actually be something to celebrate. Who knows if they will ever be able to pin down the genetic mutation you are talking about! I'm wondering in the universe of CLL folks what percent come back with a "normal Karyotype" ? And what the final typical prognosis is for that group? I was "ready" for the genetic mutations that we discuss all the time on HU but not ready for this surprise result! That is what is so weird about this disease it can be so many things. Thanks for your answer you saved me months of waiting for my next doctor appointment. If only the rest of my world were this responsive!

Be happy and well.

Many thanks,

Kathy

[tekusa in reply to kathypawpaw]

I am normal as well..... I have been trying to understand where I fit when time comes for treatment. The German study of FCR vs FC indicated normal does not do well using FCR. So frontline BCR inhibitors (in or out of clinical trials) is what I strive too. I am 57 and approval of Ibrutinib as Front Line for 65 years or older wouldn't help. That is unless things don't progress till then. I asked this question of Dr. Jeff Sharman (his blog) and he has reservations on the German results. I think others on this site do as well.... I wonder if having Genetic Sequencing performed will provide more information for Normal CLL karyotype. Below are some older discussions regarding normal. Regards!

clltopics.org/Alert/direct_...

updates.clltopics.org/2710-...

[kathypawpaw in reply to tekusa]

Thank you Tekusa,

Excellent article with lots of links to study up on which is exactly what I plan to do. I'm starting to "get" this now. So the "healthy" title is not the get out of jail free card I was hoping for! I think it is important to follow up on genetic testing again for all of us "healthy kayrotypes" especially prior to any treatment. Possibly asking to be tested for the new "6" gene defect or genetic sequencing even better. Since this is an older article they may have discovered more genetic abnormalities that they can measure predict and treat effectively. You are a young CLL patient at 57. So you say ibrutinab would not be approved for you? Why not? (Please excuse me if I ask a dumb question as I am still learning.) I hope you are feeling and doing well. What is your take on exercise and healthy eating? Do you think there may be a family link to this? In my case everyone lived to a very ripe old age without a lot of doctors, drugs or testing. So if someone in my family had this we didn't know about it and it didn't seem to impact them if it was there at all. I really appreciate the information you provided. I take great comfort in knowing I am not alone in this struggle. I thought I would be fishing for real FISH after I retired not learning about the "FISH" test! But life is still sweet if not bitter sweet at times.

All the best,

Kathy

[tekusa in reply to kathypawpaw]

> So you say ibrutinab would not be approved for you?

> Why not? (Please excuse me if I ask a >dumb question as >I am still learning.) I hope you are feeling and doing well. >What is your take on exercise and healthy eating? Do you >think there may be a family link to this?

Ibrutinab currently is approved for refractory CLL patients (Like my mother) and 17p deleted. Although soon to be approved for 65 years and older. My mom failed FCR. She doesn’t know what chromosomal abnormalities she has. As soon as Ibrutinib was approved she began taking it. Only 2 capsules not 3. She still feels bad and doesn’t like the side effects.

Her blood work looks near perfect using Ibrutinib, so much better than mine. She was diagnosed Stage 4… 5 years ago and had lots of chemoimunotherapy which didn’t work. All of that Chemo drove her immune system to the lowest it can be. She has sinusitis all the time. She gets infections easy. So she has intravenous gamagloubulin. IVIG, every 6 weeks or so. Many CLL patients do....

Dr. Byrd encouraged me to get her involved in ACP-196 trial, but mom doesn’t travel. Dr. Byrd is at OSU which is 6 to 8 hours by car. So she declined.

So as of today (and this will likely change) Ibrutinib is not approved for the very first treatment. Mostly the insurance companies will not pay, and the pills are expensive ($90/each). I have heard, online, that some patients have gained insurance approval for first treatment. So it might be possible.

MY TAKE ON EXERCISE AND HEALTHY EATING…… Is to absolutely do it, no question. I am fairly healthy for my age and work out nearly every day. And not just one routine but mix it up with different things. Bicycle, Hiking, Lift light weights, rowing machine, elliptical etc. My biggest vice is I drink to much beer and wine. I have cut back a lot since diagnosis but have not stopped. That may be the death of me! I have drank beer or wine every day for quite some time. I do eat much healthier. I suppose doing this will help my immune system. That is important I believe.....

By The Way….. My grandmom might have had CLL. She died at 94 of heart problems. Never needed treatment as her CLL would hover near normal. My Mom is 79 years old, and one feisty lady. We compare notes of our CLL all the time.

Understanding all this stuff about CLL takes a lot of work. Might even try reading how your immune system works to help to understand the various information that is discussed.

Yesterday I had a thought that I should spend more time to understand health insurance rules and requirements because treatments can be expensive. But a Cure is not far away I think.... On the other hand I think to myself is it possible to cure a Normal Karyotype without knowing the chromosomal dysfunction? Maybe some folks already have with FCR regimen.

[kathypawpaw in reply to tekusa]

Dear Tekusa,

Every time I talk to you it is wonderful. I really enjoyed and appreciate your reply to my email. I also think you and your mom are so blessed to have the most wonderful relationship ever. I love hearing about her through you. You are so lucky to have each other. I can't say that enough. Could it be your CLL has brought you even closer together? If so there is always a bright side to everything even this horrible disease if you just look. I miss my sweet mom so much so treasure every day with her as you already do. Like I said before you are a great son.

At my last doctor visit my doc (who is a hemotologist) but very well respected as the best in town told me they are doing a good job with 17p deletion with ibrutinib. Health care companies and Medicare should cover this as a first round treatment if it is the most effective thing they have to offer us. We have all paid in for many years while we were healthy so now when we need treatment it should be there. Sorry to hear about your moms chemo experience. More and more I read about getting away from chemo which makes sense since it does a number on your immune system which is already down. I love that your mom is a "fighter" and you are too!

Exercise is the hardest thing for me but I am getting better. Eating healthy especially smoothies are easier. I love wine too. I drink rarely now because it does a number on my "glands". But there are health benefits from a little red wine or beer so i think it is an individual decision to make. Life is short and if a beer adds joy to your life why not? I think all of your exercise is the most protective thing you are doing.

So yes I agree with you we "normals" need to keep trying to find the gene through testing involved so they can pinpoint treatment for us. Funny at first being "normal" sounded really great. Oh well it was nice while it lasted. If they figure mine out I will share. I think finding this community was another bright spot for all of us. So thanks.

Lastly, I am not sure if this CLL was in my family history or not. Everyone lived to be quite old so if they had CLL it was the kind that was pretty low maintenance. Good luck to you and your mom.

Have a great day!

Kathy

[kaymack]

Kathypawpaw,

I am FISH "normal" karyotype. From my understanding, we "normals" are in the mid-range risk so far as people with CLL go. I suspect as more is learned, our subgroup will be divided into several newly discovered karyotype abnormalities.

I myself was diagnosed at Rai Stage 1 and started FCR 4 years later when I had progressed to Rai Stage 1V. I'm into my 3rd year of remission now and I'm doing well.

I found this paper some years ago. It may interest you: oncology.by/uplds/ASH/MAC/w...

Cheers,

Kay

[kathypawpaw in reply to kaymack]

Dear Kaymack,

Thanks for the link you posted. We HK now find ourselves in a smaller group of the very small group with CLL. Reading is what we have to do to stay informed. I for one like to be able to discuss and understand what is going on with my health with my doctor. I guess many of us here feel the same way. We CLLers are so fortunate to have this great source of information and support. When I take an inventory of what I am grateful for this website and the souls on it is right up there. Thanks for the link.

Please stay in touch and let us know how you are doing.

Kathy

[Cllcanada Top Poster CURE Hero]

I'm FISH normal on 6 probes... it actually is a large group about 15-18%... Normal or 'not found' fits on either side of Trisomy 12 in regards to general prognosis, depending on the study.

FISH is still a good prognostic tool, especially in clinical use, to identify high risk patients for special treatment, however the focus now has turned to subclones like NOTCH1, cMYC, TP53, all Richter's involved, BIRC1, SF3B1, ATM, TP53, SYK, RB1 and a host of others, still to be sorted...

I think clinical access over the next few years of whole or selective genome sequencing will tell the whole story...

Certainly my experience of FR treatment would indicate it wasn't great, having had one month remission and a Richter's transformation... 😳

~chris

[kathypawpaw]

Dear Chris,

Yikes you guys know your stuff. I thank you for this additional information so we in this "not so small" group are on either side of Trisomy 12 depending. I realize you guys go to many CLL forums and so are going to be way more informed even if we on the website try to read and keep up and I am grateful for your kind help and knowledge. I am so sorry about your Richter's transformation. How are you getting on? I totally agree it is genome sequencing that seems to keep coming up as a way to pinpoint what is actually going on and guiding treatment. I'm here for you in cyberspace for what it is worth. Hang in there Chris. You help so many it must feel great to be so needed.

Kathy

[ThreeWs]

Hi Kathypawpaw

I would want to know more concerning what and where the cytogenetic damage is if my FISH test came back "Normal". If at all possible a CLL patient will probably get a better quality FISH test from a CLL specialist that may include other Chromosomal aberrations with FISH probes that can look at Chromosomes 2, 4, 7 & 8 in addition to the common ones we are most likely to hear about ( 13q-, 11q-, 17p, 6q & 12 trisomy). Here is an interesting example from a 2014 Blood journal research paper, Gonzalo Blanco et al., where researchers hypothesize that aberrations in Chromosome 8 may come before deletions in 17p and contribute to a worse prognosis. "In CLL patients with del(17p), detection of 8p- and/or 8q+ is associated with an increased karyotypic complexity and a worse outcome; 2. 8p-/8q+ could act as a primary event that trigger del(17p). More cases are required to confirm this hypothesis." You can see from this paper that a patient not FISH tested for Chromosome 8 defects might get a "FISH Normal" result but have the beginning of damage that could lead to a poor prognosis.

WWW

[kathypawpaw in reply to ThreeWs]

Hi ThreeWs,

Thanks for your very informative email. I am very grateful for this explanation. Yes after reading your information I have decided to go ahead and set up an appointment with a doc that is a CLL specialist from the recommended list on this website that is located relatively close to me.

I agree further chomosomal testing should be done to see if they can figure out if it is gene #8 or whatever else. I know having this information is important to treatment and I guess I would rather have it done while I am feeling "chipper". My regular doc was even very optimistic about 17p deletion which is why I like him. He says they are doing a good job treating this group too. Not sure if I buy that but that is what he said. Not happy to know that my CLL could be worse but after all that is why these tests are run right? I would rather have all the facts.

What are you throwing in your picture? A javelin? so how are you doing? Were you also "normal" at first typing? You look pretty fit which will serve you well. 50% of cancers are improved with exercise. Time to take a walk.

Thanks again for taking your time to help me.

Kathy

[tekusa in reply to ThreeWs]

Hi Wayne... With the information you provided I went to my OSU FISH report and see just now that my 8q24 (CMYC) probe was negative, but no result for 8p that I can see. I believe the OSU FISH was a 20 probe or metaphase cells. I don't understand it all! But with the information you provided I see how a Normal Karyotype might not do well with FCR if 17p is not foreseen.

[Cllcanada Top Poster CURE Hero in reply to tekusa]

TP53 direct gene analysis is the kicker... you can have no 17p deleted, but still your TP53 can be mutated or not working... and that is not great... since it is the 'guardian of the genome'.

I think it can be tested by sequencing or PCR, but don't quote me...

[Cllcanada Top Poster CURE Hero]

One of the best tests offered currently is from CGI called Complete CLL, it is quite expensive, but a few patients have got it paid in the U.S. by their private insurers...

cancergenetics.com/laborato...

But even then...you won't know the whole CLL genetic picture... and clinically,

it doesn't really change anything at the moment.

~chris

[tekusa in reply to Cllcanada]

Thank You Chris! I didn't know about this Complete CLL. It might be what I am looking for. But you are right..... the information may not change anything at this point. Good to know it is there (New Jersey) (only 2 hours from my house). I will call to see how much Complete CLL costs.

[Cllcanada Top Poster CURE Hero in reply to tekusa]

I would love to know the price... someone from Canada was quote $3200 US a year ago, if my memory serves 😳... but it may have included shipping etc. and blood needs special handling as a biohazard...

Edit

I noticed they have added a number of things to the test, so it could be considerablely more now...

[tekusa in reply to Cllcanada]

I will find out and let you know! My blood work from OSU was billed at $18,000 and settled by insurance at $13,000. I really sweated that bill thinking I might have to pay more.... than the $200 I had to pay. Thanks again....

[Cllcanada Top Poster CURE Hero in reply to tekusa]

WOW!

[tekusa in reply to Cllcanada]

Hi Chris, I called today and the price is now $3500 for the CLL Complete panel.

[kathypawpaw in reply to Cllcanada]

Thanks from me too Chris. Complete CLL test. It really helps to know what test to ask for which is half the battle. It looks quite impressive in what it measures. I hope this test is on my health plan we will see. As Tekusa says it may not change anything but I would rather know what exactly has gone "off" genenetically then be in the dark. Since treatment can be gene specific I want my health care team to have all the facts. That goes for all of us "not so" normal karyotypes across the globe.

Kathy

[Cllcanada Top Poster CURE Hero in reply to kathypawpaw]

Kathy

While it is fine to know...you need to think about the double edge sword... on the one hand if your genetics are good...then great, but if they are bad, there isn't much that can change things at the moment, perhaps a clinical trial for new treatments...

You must weigh the results you might get and understand how you will handle them...

I have know patients who have done extensive testing and had trouble dealing with what they found out...

Think about carefully... that's all I'm saying...

~chris

[AussieNeil Partner Administrator in reply to Cllcanada]

dilbert.com/strip/2015-12-07

[kathypawpaw in reply to AussieNeil]

HA ha ha ha ha........still laughing! You are a riot! LOVE IT so funny mate! It was just what I needed! Almost fell off my chair!

Sometimes we take all of this tooooooooo seriously. Which is not good for our health!

i hope everything is getting better for you. It is so nice to have a friend on the other side of the planet.

It was a beautiful day here today so I am sending it around to you!

Kathy

[kathypawpaw in reply to Cllcanada]

Hi Chris,

Thanks for your honest reply. I'm pretty sure I can handle the truth no matter what they find. I know it could be good or bad let's face it none of this is exactly good but I am determined to make the best of it. What bothers me is not knowing. It's how I'm wired. I would say it's a huge source of stress not knowing. I've always liked medical stuff so I find myself fascinated by the information I learn about this disease as if I were outside my body looking in. I also know that you may have a test that shows a defect in say gene 8 then your genes change again and become say 17p. So your results are not static. If I find out that I have a gene defect that is not treatable then I will cross that bridge when I come to it. I wish I could tell you privately why the truth is so important to me but it is. I saw a show on TV tonight on PBS that was talking about super genes. That diet, exercise, stress, and even our thoughts and the way we look at our future impact our gene health. It was an interesting show. Many thanks for the heads up anyway.

[StupidPlanet]

I'm interested in Complete CLL to reconcile two other genetic tests. Engauge CLL showed P53 mutation. MD Anderson test did not. I'm down the rabbit hole.