unmutated

[kel555]

hi all merry christmas iam not getting much response unmutated cll folk on this site is there only 4 just like to learn a bit more on the subject thats all ,,thankyou ,,kel 555

[SofiaDeo]

Are you referring to unmutated IGHV? I am one, and I know there are others. Some of us put some of our flow cytomerty, FISH, mutation status, etc. in our profiles. We may not post our markers, mutation status, etc. for every question.

[kel555 in reply to SofiaDeo]

thankyou

[Jm954 Administrator]

Hi there, your last post had an answer from Dr Brian Koffman who gave a pretty definitive answer about your likely length of remission, being unmutated and having FCR. However, it's impossible to say how long any individual person's remission will be because statistics only tell us about populations and not each person.About 40% of CLL people are IGHV unmutated and, generally their remissions are shorter than mutated patients after FCR, Having said that, the new targeted therapies are very effective treatments for relapsed CLL.

Please don't spoil your time in remission by worrying about this, enjoy your new health and do the things you enjoy when you can.

Best wishes and season's greetings

Jackie

[mikec11 in reply to Jm954]

Well said!

[kel555 in reply to Jm954]

thankyou

[WinJ3]

Hi Kil555, I am unmutated IGHV and Trisomy 12. I began treatment with Gazyva in 2018 and then Imbruvica in 2019.

If you use this HealthUnlocked site you’ll get 560 post and 99 members referencing unmutated:

healthunlocked.com/cllsuppo...

Win

[kel555 in reply to WinJ3]

thankyou

[AussieNeil Partner Administrator]

Actually about half of CLL diagnoses are unmutated IGHV. Further, because unmutated IGHV correlates with a shorter time to treatment and at least with older chemo treatments, typically shorter remissions, the majority of our members in treatment are likely to be unmutated IGHV. Remember that outside of the USA, it is very difficult, if not impossible to get your IGHV mutation status tested as it is nearly always not a factor used in treatment decisions - but should be!

Thankfully, the UK is moving to non-chemo first line treatments. Your remission after FCR may still be quite reasonable and you are now able to access non-chemo follow-up treatments where you live. There isn't the big difference in response seen with non-chemo treatments that are observed with FCR and BR in unmutated folk.

Neil

[kel555 in reply to AussieNeil]

thankyou neil

[Cfar in reply to AussieNeil]

Hello Neil I am new to all this but have been reading and learning lots from this site these past six months.

Can you point me in right direction to find out what mutated/unmutated mean please? My paperwork from my consultant doesn't state which one I am but will ask at my next appointment. Meanwhile I would like to understand more .

Thanks

Carmen

[AussieNeil Partner Administrator in reply to Cfar]

Hi Carmen,

There are some very good references from the CLL Society, Dr Jeff Sharman and Chaya Venkat explaining IGHV mutation status in this related post from 3 years ago: healthunlocked.com/cllsuppo...

After reading these, reply with any questions you may have.

Neil

[Cfar in reply to AussieNeil]

Thank you Neil. Much appreciated.

[mikec11]

As others have pointed out, always remember that CLL is heterogeneous. Meaning it is highly variable at the individual level. Some that are unmutated never need treatment. Just like some 17p can be indolent for a very long time. Science follows the herd and doctors follow individuals.

[kel555 in reply to mikec11]

thankyou

[Big_Dee in reply to mikec11]

Hello mikec11

I really like the way you put that. Well worth remembering. Merry Christmas.

[cajunjeff]

If you want to learn more about mutated/unmutated Cll from a lay person perspective, here is a post I wrote about it earlier this year:

healthunlocked.com/cllsuppo...

[kel555 in reply to cajunjeff]

thankyou

[SofiaDeo]

Yup, in my opinion saying "I have CLL" is often like saying "I have an infection". There are lots of types, causes, treatments & responses to both disease states. And I (former south Florida resident) tend to think of each major incident in my CLL as a hurricane that blew into my life. I have to deal with each incident, but try not to worry in between because like the weather, it can be unpredictable and there's no upside to worrying about it. And someone recently posted a thought I am adding to my personal mantra: it was something along the lines of "worrying about something that may or may not happen means you put yourself through it twice".

[Sushibruno in reply to SofiaDeo]

Im the total opposite and im not proud of it. I wish I could stop this constant worrying that gets to me mentally the most. I really don't want to worry about this everyday. (It's been 3 years)

[SofiaDeo in reply to Sushibruno]

But IMO Sushi, you still have some active hurricane going on right now. It's especially tough to try not to worry & react when you are actively symptomatic! Even if the symptoms are not due to CLL. The shoulder thing, your current pins/needles, on top of pandemic isolation & pandemic stressors. Ugh. You are having a hard time & I wish you weren't. Virtual hugs from me & licks from my doggie!

[Sushibruno in reply to SofiaDeo]

🙂🙃🙂 "licks from the doggie" lol thank you.

[kel555 in reply to SofiaDeo]

thankyou

[kel555 in reply to kel555]

thankyou

[cllady01 Former Volunteer]

kel, your first inquiry included those who had had FCR treatment and the question if they had had more than 3 years remission. There are many members who are unmutated, but those treated with FCR are becoming fewer as time goes on.

That may explain the few you heard from.

[kel555 in reply to cllady01]

thankyou

[HopeME]

Hi Kel I’m unmutated Trisomy 12. I had BR chemo frontline and it has held for 27 months so far. My next check up is March 2021. The CLL Specialist I have seen for about two years wouldn’t have prescribed BR frontline but he has been pleased with my remission. There is no way to know how long it will hold but he wouldn’t be surprised if I get another year or two. Hard to say but sometimes unmutated folks can do surprisingly well on chemo. Good luck!!

[kel555 in reply to HopeME]

thankyou

[Me2AsWell]

If it helps ... a layman's comment: I am 11q deleted, unmutated and entering my sixth year post FCR ... slowly relapsing and a bit lumpy but feeling fine, and stringing it out in splendid isolation to reach the summer before I go for the next intervention - ibrutinib or venetoclax? There really is no point in letting CLL worry us - worry won't cure it (believe me I've tried this route) ... the scientific horizon keeps expanding in front of us and I am optimistic! All the very best from another fellow traveler on this journey.

[Smakwater]

kel555,

It looks like you have plenty of responses that addresses the prognostic aspect of unmutated CLL.

A patients view for Unmutated CLL can be explained by stating that a percentage of your immune system cells will not complete maturation at the measure in your blood called the Heavy chain region. For the most most part, the underdeveloped cell is missing a receptor which renders the cell useless in gathering foreign invaders in your blood.

The receptors on the cell at the Heavy chain region of which some are missing when unmutated, are depicted in medical illustrations as Y shaped arms protruding from the cell. These arms grab the invaders and hold them captive until another cell armed with a lethal immune capability adjoins it.

To my knowledge, an understanding of the poorer prognostic measure that was previously associated with unmutated IGHV during the time when FCR was the treatment standard has yet to be defined. However as some have already stated, the poorer outcome measure is now less with the newer treatments.

One could hypothesize that because unmutated cells are not effective immune protectors, that the poorer previous prognosis may have been influenced by that condition. Especially with treatments that are less targeted and with a greater toxicity profile such as FCR.

Here is a video with written transcript that may help you with some visualization -

khanacademy.org/science/bio...

JM

[AussieNeil Partner Administrator in reply to Smakwater]

In recent years, an alternative theory into the cause of the difference between mutated and unmutated IGHV CLL has gained acceptance. For decades, the accepted theory was that the IGHV mutation status fitted in with the maturity stage of the B-lymphocyte when DNA changes resulted in it becoming cancerous. This theory nicely fitted in with the observation that the earlier in the B-lymphocyte lifecycle a cell became cancerous, the more aggressive (acute) the cancer - and there are lots of B-lymphocyte blood cancers. So IGHV mutated CLL was a more chronic disease.

Many researchers now consider that the IGHV mutation status reflects the CLL cell's ability to self repair itself after cell division. DNA repair isn't always perfect, so when repairs are made, there are slight differences in the amino acids between the germline original (what you inherit from your parents) and the copy. It's this variation that is measured in IGHV mutation percentage, reflecting the ability of the whole CLL cell to make a faithful copy of the original clone, so there's actually a continuum from unmutated (copy correction not working) and mutated CLL. Hence unmutated CLL is more prone to developing major genetic errors, correlating with a more aggressive version of CLL. Interestingly, we've had quite a few members over the years questioning whether their IGHV percentage variation from their germline B-lymphocyte progenitor put them in the mutated or unmutated group.

Neil

[wroxham-gb in reply to AussieNeil]

Thanks Neil. That's the first time I've seen this in writing but so definitely true (at least in my case).Best wishes to you.

Sue

[JustAGuy in reply to AussieNeil]

Hi Neal, is what you describe above regarding newer ideas regarding IGVH mutated status in line with the Khan academy video that Smakwater referenced, or is it newer than that explanation?

Thanks for your posts!

[AussieNeil Partner Administrator in reply to JustAGuy]

That reference just describes the normal somatic hypermutation process that B-lymphocytes go through with the assistance of (CD4) helper T-lymphocytes, without reference to CLL. It's this process which produces the maturing form of the B-Lymphocyte with a differentiated B-Cell Receptor specific to antigens/antibodies from either a vaccination or an infection, which enable you to fight off infections. So it's the older explanation behind the difference between unmutated and mutated IGHV. As the Khan Academy video describes, maturing B-Lymphocytes either grow into memory B-lymphocytes, so your immune system responds quickly when it next encounters the infection causing bugs, or into plasma cells, which churn out billions of antibodies which help you overcome the infection, often unawares.

Khan Academy is a great resource to help you understand the immune system. Understanding this normal B-Lymphocyte maturation process is also important in appreciating why, with CLL, we often don't respond well to infections during watch and wait (due to CLL exhausted helper T-Lymphocytes), or during and for a while after treatment, when we have little to no healthy B-Lymphocytes. This is a common result of many CLL treatments, including some non-chemo treatments, which can also cause reduced T-lymphocyte counts. This is why it is best to get (non-live) vaccinations done early in watch and wait and preferably before treatment, though a vaccination may provide some T-lymphocyte based immunity and boost memory B-lymphocyte numbers to previously encountered infections.

While vaccinations may provide some protection if given during or just after treatment, they are generally more effective if given some time after treatment and a booster vaccination given for vaccinations done when less effective if at all possible. Some doctors actually check how effective vaccinations have been by doing an immunoglobulin titration test, which measures the specific levels of vaccine produced immunoglobulins.

Neil

[Smakwater in reply to AussieNeil]

Yes, Every door than opens reveals seven more doors.

[Big_Dee]

Hello kel555

There are a lot of people on here that are un-mutated, like myself. What is it you would like to know? Merry Christmas.

[Janie67]

I understand, I’m new at this!! 🤶🎅

[DelrayDave]

As others have said, those like us have shorter time to treatment. Mine was immediately after diagnosis. Also, the "old" chemo drugs like chlorambucil are less likely to work well. I got a 1 to 2 year remission. But now I am on ibrutinib for 6 years with no sign of the disease. Side effects are the problem. Good luck.

David

[ABP45UK]

Just a quick reply as I too have unmutated ighv. Had FCR in UK two years ago and doing fine. I know I will need more treatment at some point as this current remission won't last forever but there are great new drugs available and many more combinations being trialled all the time . So try not to worry about your unmutated status as there are many many more options now than there used to be.