CLL with “normal” FISH

[Luap001]

Hello so while I am diagnosed with CLL, my FISH was normal meaning any abnormalities were not present in amounts sufficient to be detected. And while my diagnosis is recent, I have probably had CLL for five years without knowing it because my lymphocyte count has been high enough all along. It’s only recently that I took the step of having it further evaluated. So my question is whether any of you have had a similar experience in the past and how did your story unfold; how long from the time you had a CLL diagnosis with normal FISH till the time the abnormalities were detectable and identified? And what abnormalities did you end up having? I am thinking I have an indolent disease because the abnormalities cannot be detected five years in. But while that’s logical it is still pure speculation. I will talk to my doctor about this tomorrow and I will hopefully learn more. But what our group has learned and experienced collectively I think is invaluable. So please lmk if you have been down this particular path. Thx.

[lankisterguy Volunteer]

Hi Luap001,-

We had a similar discussion 4 days ago- you may want to read this reply

healthunlocked.com/cllsuppo...

and then the entire thread.

healthunlocked.com/cllsuppo...?

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The bottom line is that your own history & trend of CLL progression (tempo- see Dr. Lamanna's video communityview.lls.org/artic... ) is a far better predictor of your future than anything the doctors can measure or any advice another patient can share.

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Len

[Luap001 in reply to lankisterguy]

Thanks for the link. It does make sense in the here and now regarding my specific care. I have to say though that if I knew there were a way to eliminate the cancer cells with very modest side effects, I would wish to do so now rather than await progression to symptoms. No matter how we stratify the cancer genetics, I’d rather be rid of those cells! Again, the risks would have to be “very acceptable”. We may not be there yet but I hope that is where we are headed. If for example they have a trial with MR1 restricted CAR-T for treatment naive patients, and if the safety thereof becomes solidly established (that truly the MR1 target is found only on malignant cells and not normal cells), sign me up!

[lankisterguy Volunteer in reply to Luap001]

Please see this pinned post for an in depth discussion of early treatment vs. watch & wait. Please read Dr. Furman's recent comments at the bottom of the replies. healthunlocked.com/cllsuppo...

Len

[cajunjeff]

Luap, to my understanding a normal FISH test does not mean one does not have any chromosomal abnormalities causing their Cll. Rather it means one does not have any of the four typical types of Cll that FISH is designed to find (13q, trisomy, 11q and 17p).

So I would not conclude your Cll is indolent because your FISH is normal. The better predictor is what Len writes. If your wbc, hemoglobin and platelets are stable and your lymph nodes are not swelling up over a period of time, that’s a better predictor.

A normal FISH test for those with confirmed Cll is generally thought to confer an intermediate prognosis, somewhere between 13q and 17 p.

Not all about Cll is known and chromosomes other than 11,12,13 and17 can be involved. The prognosis for a normal FISH can be very variable.

Even with known markers like 13q and17p, the course of Cll can be variable. Some with 13q will need treatment right away and some with 17p can be years in watch and wait.

Markers can have value in informing our treatment choices. They can also be stressors.

It’s hard to know at diagnosis how long we have had Cll. I could be wrong, but I don’t think just because your FISH is normal that you can work backwards and get a reliable estimate of how long you have had Cll.

Here is an article I did on Fish testing:

healthunlocked.com/cllsuppo...

[Luap001 in reply to cajunjeff]

I think the lymphocytosis threshold over 5K is a likely indicator of CLL. I have been well over that for at least 5 years. And I have no symptoms. But what you say does make sense - we can’t assume that what is most common among aberrations is all that there is to consider. I agree therefore that the disease “tempo” is a good guide to direct treatment. Still, as I have posted, I’d get rid of my CLL if the right opportunity presented itself even if I were asymptomatic and otherwise untreated at the time.

[SofiaDeo in reply to Luap001]

You also have to remember, "lab values" are defined by 2/3 of a population distribution. By definition, there will always be people who can exhibit the disease outside these "numbers". And it's also not necessarily the "pure number", it's also the ratio of lymphocytes to your other cells. If all your "normal" cell numbers are higher than "average" patient, can you even say you have a disease?

ncbi.nlm.nih.gov/pmc/articl...

Even "low number" lymphocytosis over 5.0 does not necessarily progress to CLL, or mean you have CLL. It means you have lymphocytosis.

ncbi.nlm.nih.gov/pmc/articl...

[lankisterguy Volunteer in reply to Luap001]

Hi Luap001, A minor correction the 5K threshold applies to the cancerous / clonal B cells, not your ALC or Lymph#. You would need a FLOW test or MRD test to distinguish the good Lymphs from the clonal ones.

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See ncbi.nlm.nih.gov/pmc/articl....

SNIP Chronic lymphocytic leukemia (CLL) is a clonal lymphoproliferative disorder characterized by >5 × 109/L peripheral B-lymphocytes coexpressing CD5, CD19, and CD23 and a weak expression of CD20, CD79b, and surface immunoglobulin (sIg)

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Len

[Big_Dee in reply to Luap001]

Hello Luap001

I wish it were that simple. I have very aggressive CLL. After treatment my lymphocytosis was 1K so as my CLL Specialist explained to me, technically I do not have CLL, but we both know I still have CLL. Due to previous blood tests, I know I did not have CLL 6 months before being diagnosed with CLL, which required treatment 14 months after diagnoses. I think everyone understands your desire to rid yourself of any cancerous cells while you are void of symptoms. We can only hope to one day get to that point in treatment. Blessings.

[Mystic75 in reply to cajunjeff]

Great explanation..

When my husband was first diagnosed, his Fish test was 'normal' but he had t(14:18)...I really wish they would change it because it is so confusing and misleading for new patients.

[cajunjeff in reply to Mystic75]

I agree. It would be very easy to add some short and simple stock language to FISH report explaining better that a normal FISH report does not mean one does not have a chromosomal abnormality causing their cll, only that one doesn't have the abnormality FISH is designed to look for.

So why doesn't FISH just look for all abnormalities? That's like saying why not look for every fish in the entire Pacific ocean. Our chromosomes cover many "miles" of microscopic territory and looking in that detail at every part of every chromosome and every gene would take a lot of time and be an absurdly expensive test I would imagine.

[Luap001 in reply to cajunjeff]

My doctor today basically said as much. He said though that since my counts have been in the CLL ballpark for about five years and since I still don't have any symptoms, that suggests a non-aggressive disease. He did say that sometimes you can get new mutations along the way that could change that even in the absence of treatment although generally it is more likely with treatment, even targeted therapies. Therefore he said as long as there are no symptoms and no rapid rise in the clinal cell count, he said I should just live my life. The follow up (I. The absence of any complaints I might have) is every three months and if he were to see a significant increase in count over that time, he would increase frequency to monthly to see if the increase extrapolates to a 6 month doubling time. And as far as the COVID vaccine, he says he does recommend it although it has not been thoroughly studied for cancer patients. So basically it’s a matter of the risk of the vaccine versus that of the disease. Of course that presumes the vaccine is effective in cancer patients. If you are really quiet, you can hear the ghost of Benjamin D’Israeli whispering...

[Bell53]

The only thought I might add is to have the TP53 test done. I am Fish normal but TP 53 mutated - which cans also mean shorter time to treatment

[Luap001 in reply to Bell53]

TP53 was performed and it was not mutated. I will let you all know if the doctor says anything interesting tomorrow.

[Lunaril]

I'm in the same boat. Diagnosed with CLL in 2019, normal FISH, but my white count has fluxuated between 14k and 21k during every blood test, my leukocytes are through the roof and over the last year I've noticed intense and overwhelming fatigue to the point where if I exert myself to much I and winded and need to sleep. Had to give up a streaming career due to the medical stresses of my condition. Seen a dozen specialists, no answers other than CLL watch and wait, while my health declines rapidly. I can feel something is very wrong, but can't get any of my doctors to listen or help. Last week finally asked for second opinion from doctors in Pittsburg to hopefully find someone who will start a treatment to help before it's to late. I noticed my health declining, during a period where I was exercising and starting to lose weight. Went from 325 to 260 before started having symptoms of cyanosis, bluish nails and lips when exerting myself. Seems like decline has accelerated over the last year. Also noticed a new onset of gluten allergy, that could potentially be traced back to GMO wheat intolerance, based on educated guesswork and experimentation with diet. Would be interested in touching base with you to see if we have any similarities which may help our healthcare teams.