Had PET scan yesterday, read the report today. I haven’t spoken to my Doc yet. But according to this report there are no signs of enlarged lymph nodes anywhere. Kind of blows my mind, the main reason I started treatment was because of my abdominal pain (which I still have). I am considered high risk with poor prognosis (according to the genetic testing report). Trisomy 12, unmutated , notch1,NRAS, ATM and MITF. I must say, I am pleasantly surprised how well this combination has worked for me so far. I hope it lasts. Btw my oldest sister just started the exact same treatment, different hospitals and different doctors. She is a 13q del. Her wbc went from 180.000 to 7,000 first week. GAZYVA and Venclexta is no joke. Now, I still have to figure out what my pain is…
GAZYVA & VENCLEXTA…I thought it wasn’t working... - CLL Support
GAZYVA & VENCLEXTA…I thought it wasn’t working. Apparently it was, extremely well
Love the title and thanks for sharing whats going on. I am just finishing up my 9 month on O & V treatment. I must say, although my left side and upper abdomen are way better. I am still quite bothered by that pain. It limits what I do physically. I can eat fine, not loosing weight since treatment started.Sound familiar?
I just read your bio, you’re quite the writer. Crazy how similar we can be with others and yet different at the same time. I am sorry to hear about your symptoms from the treatments. And the problems getting the infusion site, I have the same nurse you had and I also allowed her to practice on me. Lol. I really haven’t had any adverse reactions to the infusions or the venclexta almost to the point where I thought it wasn’t working. I am guessing I will have a few more doctors to see (fun) to try and figure the pain out. Someone had mentioned diverticulosis, location seems possible. I guess it’s as good a place to start as any. Stay healthy.
Congrats that is great news!!! Zanubrutinib works amazing too, in 3 days my enlarged neck lymph nodes disappeared after being there for over 10yrs. I also have recurrent stomach aches when the diagnostic test see nothing but shrinkage. Someone here said that with the shrinkage, other organs are moving around & it may take time for the body to readjust to the change. Wow that’s great news, UMRD seems to be in your near future🎉🎉🎉
So happy for you!!!
God bless
Skipro
Hey Skipro, I will be the first to tell anyone how effective Zanubrutinib really is, just magical. But what I believe they made all those great drug reduction options for, was doctors to use those options as need be. My bloodwork is near normal on 1/2 the dose. Full dose was worst then the CLL W&W period of 13yrs 8mos 🙅🏽♀️ The cure can not be worst than the disease 🦠
I am good on the drug but with the damage it did for 3 months without proper treatment to my heart & lungs, will that ever resolve? These 30lbs weight gain because I could not workout for the 8 months its taken to adjust to the medication. Plus the medication affects my bones too. I was on 80mg daily from July 28-Oct 29 while my heart & lungs healed & my WBC/ALC were still dropping, Hgb @12.5 rising but Platelets were not moving @80s.
I increased to 80mg twice daily 11/28, 2023, I caught a cold, Plts dropped & the bone pain intensified. But 2 weeks later I noticed a big drop in Lymph % high 80’s to low 70’s, then the Plts rebound from 60, 90 & now 106, WBC 11 from 81, Hgb 11.9-12.5. Zanubrutinib is amazing but you must be properly monitored & managed!
I took Venetoclax with Rituxan for a year from 2017-2018 and have been in remission for five years.
What is your ALC count now?
Mine says 1.0, Is that too low?
Not really. As far as I know a healthy person has it around 1.5. A combination of B cells, T cells and natural killer cells. The more interesting question to which normally nobody knows the answer is how much of the ALC belongs to each of these.
The immunophenotype (flow cytology) test reports how many healthy and clonal (CLL) cells make up the ALC, along with the number of natural killer. helper (CD4) and cytotoxic (CD8) T cells. The CD4:CD8 ratio is also reported from the latter two counts and is fairly commonly reversed in CLL due to CLL driving an increase in CD8 (cytotoxic) T cells. There's normally no need to repeat the test after diagnosis, because CLL cells begin to dominate the ALC count and also you hopefully get a dramatic fall in ALC with treatment. Unfortunately, most of us don't even seem to look beyond our WBC! 
Both my doctors affirmed that, my WTC never went over 18,000. And had actually dropped on its own to 11,000 right before treatment. Didn't make sense to me.
CLL cells do eventually die, it's just that they don't die like normal lymphocytes. It's the reason about 1/3 of us never need treatment; eventually some old CLL cells will die off. The problems are related to things like are they growing so fast they are growing into lymph nodes making their size increase/affecting other things, are they infiltrating the bone marrow such that one isn't able to make red blood cells, or platelets, or neutrophils. Does one have severe fatigue, or is one losing weight, are there serial infections, are there other unexplained symptoms.
So it's not the *absolute number of CLL cells in the blood* that determine treatment. You haven't mentioned lab results, or if a bone marrow biopsy was done to look at degree of infiltration. When other cell lines are affected, and/or certain other symptoms are present, doctors recommend treating, whether or not you recently have had a significant die-off of old CLL cells. Whether or not lymph nodes are enlarged, or if bone marrow infiltration is comparatively low.
Does it mean that patients in UMRD remission have healthy B cells as part of the ALC and if so, why are they still considered immune compromised?
Hopefully, eventually healthy B cells are again produced by our bone marrow after time limited treatments have been completed and when our bone marrow has had time to recover. That can take several months or more - and up to a year or more after the last obinutuzumab or rituximab infusion. With maintenance and CAR-T/CAR-NK therapy, healthy B cells are continually targeted while the CAR lymphocytes remain active, so healthy B cell levels may never be significant. Hence the need for maintenance IgG infusions, because there's no replenishing of antibody producing plasma cells from new healthy B cells.
Unfortunately, it's not just healthy B cells that are impacted by CLL and CLL treatments, particularly with the older chemoimmunotherapy treatments. The T cell CD4:CD8 ratio imbalance can persist perhaps indefinitely as can other systemic effects on the immune system, such as T cell exhaustion. This is why CLL researchers see restoring the immune system as the major outstanding goal in providing a complete cure for CLL
Neil
Thank you. That's a big advantage of time limited therapy.
> Does it mean that patients in UMRD remission have healthy B cells as part of the ALC and if so, why are they still considered immune compromised?
I think this is a really important question.
I would say that based on my own experience, if we test uMRD while on treatment, we have almost no healthy B-cells.
It could depend on which treatment - anti-CD20 Obinutuzumab or Rituximab by themselves suppress immune recovery for a year or more after the last infusion. I expect that immune recovery after BTKi or BCL2 monotherapy or combo-therapy happens faster, but I can't yet point to a graph that shows what's typical, and what's not.
Immune recovery is mostly monitored by Total Immunoglobulin testing, but that's a further development of B-cells. The B-cells need to mature to become Plasma B-cells, and then make the antibodies. There's so much involved in that development chain - naive B-cell growth in marrow, exposure to a pathogen, B-cell activation in lymph nodes, etc. Even the textbooks are confused what happens when and where.
One of the things I like about ClonoSEQ MRD testing on my trial is that it both identifies and counts normal and CLL clones. I will be having periodic ClonoSEQ tests after treatment to compare that to Lymphocyte Subset Flow Cytometry, and Total Immunoglobulin counts. I'm just not sure how often - quarterly, semi annual, or annual ClonoSEQ and Lymphocyte Subset Flow Cytometry. I'll certainly get Total Immunoglobulins quarterly.
=seymour=
LeoPa -
> The more interesting question to which normally nobody knows the answer is how much of the ALC belongs to each of these.
At M.D. Anderson, I get fairly regular Lymphocyte Subset Flow Cytometry that counts CD19, CD3, CD4, CD9. CD16, and CD56. On my aggressive first-line regimen of pirtobrutinib, obinutuzumab, and venetoclax, the CD19 (B-cells) have been 0 since Cycle 4. So my ALC is all T-cells and NK cells with a very few B-cells below the sensitivity of flow cytometry (1 in 100K-200K WBCs?). I suspect that anyone who achieves any level of uMRD has almost no B-cells at all until sometime after treatment.
=seymour=
Still in remission after 2 years of completing my one year Obinutuzumab and Venclexta regimen. Good stuff, for sure!
My husband only had Gazyva and less than 4 months of Venclexta and never more than 200 most of the time on 100 mg. or less and was NED on both testing and bone marrow biopsies. Still in remission over 2 years later. ALC in the 4 range. And he is 84 years old. It was his third round of Gazyva which is responds extremely well to. He had a 2 year remission on Gazyva alone on the second round and his first round which was Gazyva and leukeran gave him 2 free years as well. Wishing you continued success.
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