Hi all
Diagnosed since this past June. Started on Brukinsa due to 6mm Supraclavicular node. Tolerating well on reduced dose of 240mg. I have a Notch 1 mutation and a normal FISH. No one has ever mentioned this mutation to me and was afraid to ask. Can anyone give me information on this. Also negative D38?
Also I keep hearing we won’t die of CLL but other causes. Like what? I’m a retired nurse and health educator and I am always seeking knowledge but sometimes knowledge can be scary.
I've combined your posts and added a descriptive title.
CD38 negative correlates with a long period in watch and wait and longer remissions. 'Normal' FISH is also associated with a good outcome, with only 13q del better. NOTCH1 is a less desirable marker, but there's not the amount of data with this marker compared to FISH and CD38 results. You should respond well to Brukinsa/zanubrutinib.
About 30% of those diagnosed with CLL never need treatment. There's a greater risk of fatal infections with CLL along with a higher risk of some secondary primary cancers, in particular skin cancer. Hence the importance of vaccination and regular skin and other checks for cancer respectively.
Neil
Thank you. I try to put that little devil in the back of my mind but I had to ask. So far only going on 4 months now my physical life has basically remained the same. It’s the mental! I torture myself with the thought “when is it going to change and I start feeling sick” trying to overcome that battle.
Hi Reetywell, I'm just a W&W patient diagnosed in Feb '24, but I also have the Notch 1 mutation which is one of the more common mutations (roughly 10%) found in CLL patients. I recently spoke to both NIH doctors and my MSK doctor about this exact question. The bottom line seems to be that with the Notch 1 mutation our CLL cells don't turn off their signaling the way wild type Notch 1 does making for a more aggressive form of the disease. Notch 1 is common with Trisomy 12 and seems to be more tied to unmutated IGHV. It also raises some concerns for Richters.
I had a blood draw last week to determine my specific IGHV sequencing to see if I have the 4-39 rearrangement which has been tied to a higher RT risk.
Here's a 2019 and 2008 article that speaks to this. I'm sure others can add more specifics as I'm just learning this stuff too.
ascopubs.org/doi/10.1200/JC...
ashpublications.org/blood/a...
Bigfoot
Thank you for responding. What you said is confirming what I have researched. One possible difference is I am not trisomy 12 and am negative for all chromosomes. I am also CD38 negative. Does this change the out look at all. Searching for hope for a future living with SLL/CLl.
I'm not sure. I've had 2 flow tests. One said I was CD38- the other said CD38 "normal". When I asked if this was positive my CLL specialist said it used to be used heavily as a prognostic factor with ZAP70, but IGHV testing has largely usurped it's importance.
When were you diagnosed and have you ever been in remission?
Diagnosed Feb 24. I'm in W&W with SLL presentation. I have some enlarged nodes, mostly pelvic/mesenteric. My ALC is normal.
Hello Reety. I am not an expert on cll, or much anything for that matter. Lol. But after my diagnosis I read a lot about different cll markers. Truth be told, I obsessed over them a bit.
Many of us, if not most, have some mix of good and bad markers (discordant markers). For the most part I think they can act to offset each other to some degree. CD38 status often correlates with IGHV status. Most people who are IGHV mutated are also CD 38 negative.
I would think in your case being CD38 negative is still a very good marker for you, despite having a Notch 1 mutation. I think even if you have unmutated ighv, being CD 38 negative still helps. Put another way, if you had two large groups of cll patients, one group IGHV unmutated and CD38 positive, and one group IGHV unmutated and CD 38 negative, on average, the group that is CD38 negative will do better.
Many discordant Cll markers offset like this, but some do not. Having 13q cll alone is a good thing, but I don’t think 13q helps much if one is also 17p positive.
While IGHV status rarely changes, CD38 status can. But it usually does not. There is a strong correlation between being CD38 positive and having aggressive cll, so again I think you can view being CD38 negative as a big plus.
The problem with markers is that they are not a guarantee of anything. You can have poor makers and do well. You can have good markers, as I do, and still have cll act more aggressive, as mine has. The analogy I like to use is the weather forecast. We have all enjoyed beautiful sunny days when there was a 90% chance of rain. And we have all been rained on when there was but a 10% chance of rain. There are lots of people on here with some bad markers mixed in who are doing great.
Add to that, the new meds we have available to us work very well with most all types of cll. I think you, and most everyone diagnosed with cll today, have an excellent chance to live a long time, if not your life expectancy, and manage your cll where you can live a normal life. And that’s with now existing meds, not considering the new and better meds that should come along.
I spent my first few years with cll worrying about all this. Eight years later I’m still kicking and do not feel particularly limited by my cll. I take a couple pills a day, I have many friends without cancer in worse health.
Here is something I wrote trying to dumb down cll for newly diagnosed folks. Good luck to you.
healthunlocked.com/cllsuppo...
I read your story and hope to God I will be able to give the support information and wisdom as you have I wish I could print that out. After asking my question today a sadness came over me and that’s not me. I love life and I am very active and intend to stay that way. Thank you for lifting me up and many others. Btw what is IGHV? Do not remember seeing that in my reports.
This might help:
healthunlocked.com/cllsuppo...
Thanks again. Heavy stuff 
Another question and then I’ll quit for today lol I am Rai Stage 1. Can you explain?
There are two staging systems used internationally for CLL, Rai, (after Dr Kanti Rai in NYC) and Binet. For details, see lls.org/leukemia/chronic-ly...
Neil
This was a very informative and uplifting reply. Thank you so much. My markers are all good so I don’t worry about them too much.
Here's a great video on the subject though pretty technical.youtu.be/xpozky_VoM0?si=pXt...
Thanks but a little over my head. Just made me feel I am at higher risk for RT which is why I didn’t want to explore. See my doctor in November with ct and labs. My labs have been wnl as I am sll presentation.
Also I keep hearing we won’t die of CLL but other causes. Like what?
Once you make 80 in UK, Dementia and Alzheimer's disease becomes the highest ranked killer. The US with a median age of 77 may have avoided this.
Before that for males it's heart disease and other cancers for women.
ons.gov.uk/peoplepopulation...
Dementia and Alzheimer's disease ranked 7th in US. Heart disease comes in 1st. Cancer 2nd, probably the same ones listed for UK.
cdc.gov/nchs/fastats/leadin...
A lot of the unintentional injuries for younger people will be road traffic accidents. I'm deaf, so being run over by a truck or bus I didn't hear is always a possibility.
I read that we usually due from sepsis when an infection such as pneumonia sets in and our reduced immunology cant deal with it?
Yes. Sepsis/infection is a CLL patient’s Achilles Heal and it is something we must all be educated about and on guard against. The below link is to a thread about Sepsis that I found particularly useful. I have saved it so I can refer to it when necessary.
healthunlocked.com/cllsuppo...
Best,
Mark
I am on a watch and wait before hopefully being given Brukinsa. The re-emergence of nodes , after 2 years of remission, they say are only small. However I get a period of raised temperature every day - sometimes as high as 37.8 and often have to go to bed. However a paracetamol or Ibuprofen always resolve it so I presume not at the sepsis stage. The hospital seem to view this as normal CLL symptoms but it does restrict my life. My CLL is Richters which is more worrying!
While a Richter's diagnosis is frightening, the good thing about Richter's is that unlike CLL, it is curable. So having been successfully treated for Richter's 2 years ago, it's probable that your re-emergence of nodes is due to your CLL remission ending, not Richter's recurring. I expect you'll appreciate from your experience with Richter's how much more aggressive it is compared to CLL 
My end of my CLL watch and wait was indicated by the same symptom you have noted that you may be developing. In section 4. Indications for Treatment
of the iwCLL CLL Guidelines, we have:-
7. Disease-related symptoms as defined by any of the following:
c. Fevers >100.5°F or 38.0°C for 2 or more weeks without evidence of infection.
So please record when you have these high temperatures, how high they reach and let your CLL specialist know about them.
Neil
Thank you for this information AussieNeil. I just presumed the nodes found on scan and the symptoms were caused by Richters so this was comforting advice. I will start recording temps to take to my next appt at end if October
12 years since diagnosis and review of prior labs indicate it may have been creeping up on m e for a couple years before that. Did several rounds of IV off an on. Have been on Brukensa/Zanibrutinib for 2.5 years with decreased dose after 6 mos. Only issues with med is serious petechiae on forearms (cosmetic problem mostly) and with CLL is fatigue, but at 82 that might be the case anyway. Mostly we die of pneumonia or other cancers. Still active senior. Let go of the anxiety and live your LIFE all you can - carefully.
You were my age when diagnosed at 70. Good to know you are still active at 82!
Reetywell71 -
I have a NOTCH1 mutation and am Trisomy 12, unmutated IGHV. My doctors at M.D. Anderson, including the renowned Dr. Phillip A. Thompson, strongly denied that NOTCH1 inevitably or even mostly leads to Richters. I went through PET and a core biopsy of a large lymph node on one side of my face that excluded Richters.
I completed a trial of Pirtobrutinib, Obinutuzumab, and Venetoclax this past February, 2024, with complete remission, and uMRD6 in blood and marrow. Still uMRD6 at my 6 month follow-up. I'm 69 years old.
So many of the NOTCH1 papers that I've read or which have been cited are over 10 years old, and seem based on a small number of cases back then, because gene sequencing was hard. Patients then did CIT (cytotoxicCchemo-Immuno Therapy, like FCR and BR, and patients were diagnosed at later age and stage than now. CIT itself is associated with a higher risk of Richters. More recent papers using NGS (Next Generation Sequencing) of patients on targeted therapy haven't had enough time to follow all the cases to get statistics like OS (Overall Survival) and Richters. OS is skewed considerably by age at diagnosis.
So NOTCH1 has a perhaps undeserved reputation for short W&W and short Overall Survival. I myself had a 12 year W&W. For every marker, there's a range of outcomes. Some outcomes cluster more tightly than others. Some markers depend on other markers. We are not the average.
So I gave up trying to tease out any real-world prognosis based on NOTCH1. I know it's there. I hope you'll do really well despite the color of this particular cloud, because most of the sky is blue for you.
=seymour=
So encouraging Seymour especially when we are in the beginning of this journey! You have made my day😊
Very reassuring reply!
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