My bf is newly diagnosed and doesn’t have next doctor’s appt for a few days. He just got the results for the CLL FISH panel and I’m trying to get a preliminary sense of what the implications may be. Thanks for any help!
“RESULT: POSITIVE FISH RESULT for TRISOMY 12 and DELETION of 13q14.3; NEGATIVE FISH RESULT for DELETIONS of 6q, ATM and TP53 (17p13.1) INTERPRETATION: FISH analysis showed deletion 13q14 in 12% of cells and trisomy 12 in 31% of cells.”
Trisomy 12 is the only one of significance and it is at 33 % which is low and may not need treatment for some time. The good news is that when you need treatment there are numerous oral pills that work well on Trisomy 12. The days of IV chemo are coming to a close with the new oral treatments that you administer to yourself at hom and do not lose your hair. The 13 q14 is at 12 % and may never be much of a problem. My wife's was at 92 % and they still put her in W and W for a year. (Watch and wait or as some call it watch and worry) The oral pills for trisomy 12, (Imbruvica, Venetoclax and Acalabrutinib, etc.) take care of 13q14 at the same time. Conclusion: you are probably going to be around for along time.
Thanks for the reply. I assumed that the test would just show either positive or negative for each abnormality. So I wasn’t expecting to see the percentages. If deletion of 13q14 is considered more favorable, wouldn’t you want to find it in a higher percentage of cells?
Hello karmacrepe
I suspect 13q deletion is easiest to repair. I was told my 13q deletion was good prognosis, but that turned out to not be the case as IGHV unmutated status trumped 13q deleted. I started out with 13q at 53%, then 64% and finally 87% right before start of B+R treatment. After B+R treatment, I was 13q normal. Blessings.
The genes are not "repaired". The cells that express that marker and the cells in the marrow that make cells with that marker are destroyed. Then the marrow has to regenerate from the hopefully good cells that are left.
Hello Skyshack
Yes I know, repair was the only short descriptive word I could think of for regeneration by bone marrow.
There's data coming out that CLL cells may hide out in lymph nodes, successfully avoiding treatment, and replicate themselves. So the theory is that while it can originate in the bone marrow like most cancers do, persistent CLL may be from these stubborn cells. AussieNeil sent me this link:
Hi karmacrepe,
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We are glad you are asking for help, but for nearly all patients that information is not alarming and does not need immediate treatment. So you can relax and help your bf calm down and wait for the doctor appointment. If you can attend with him and ask the doctor to allow you to record the discussion on your cell phone, that will help you both listen to replays.
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I have a Trisomy 12 diagnosis first identified in 2008 and that is considered a moderate or intermediate diagnosis, the 13q deletion is the most favorable type of CLL diagnosis.
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This link will take you to a response I wrote 4 days ago to a similar question:
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Len
Thanks! I’ll definitely check out the links. So does the 13q14 deletion offset the trisomy 12 in terms of prognosis? Also, what kind of test is done to determine IGHV mutational status? I thought they were testing for that as well but I don’t see it with the other results.
In Australia, I had the Molecular Haem - IGHV somatic hypermutation analysis test done. The stated test principle is "Next Generation Sequencing of the clonal rearrangement of IGHV to determine percentage homology/"mutation status" relative to germline reference."
Trisomy 12 offsets 13q del, with the degree of Notch-1 expression (a separate test and not that readily available, particularly outside the USA) being a significant factor. IGHV mutation status usually has a strong influence, but your bf's best guide is the rate at which his blood counts and node and spleen sizes change over time.
Neil
They released more of his lab results today, it says his IGVH gene is mutated. Does that lower the risks associated with Trisomy 12? Would it be helpful to test for Notch-1 expression? Thanks!
Mutated is much better than unmutated. I’m Trisomy 12 unmutated. I was diagnosed six years ago this October. First treatment was about six months after diagnosis and the second treatment four years later. I believe the unmutated nature of my disease resulted in the quicker time to treatment. With a little bit of luck your boyfriend won’t need treatment for a number of years. The CLL specialist will likely test for some of the normal issues with Trisomy 12 such as Notch-1. Anyway, your takeaway for today should be he is mutated. That is great news. A big win.
Best,
Mark
IGHV mutation status is recognised as the prognostic marker with the strongest influence, both for time to first treatment and (until the newer, targeted treatments began replacing the older, "chemo" treatments that work by disrupting DNA copying during cloning), remission length after treatment. With the newer treatments, that difference in remission length has largely disappeared. Importantly, it's the only marker that isn't likely to change over time.
With respect to Notch-1 testing, our knowledge of how that influences outcomes, has primarily only been studied through CLL research establishments in the USA. I think we need much wider testing to reduce the statistical uncertainties that you get without wider international testing. I'd recommend your bf find a CLL specialist who can best inform him of what testing is worthwhile at this stage and who can inform him of its relevance. Keep in mind that prognostic markers are only useful for predicting the likely outcomes for groups, not individuals. That's because there are so many drivers for CLL which can change over time due to what's termed clonal evolution. It's why CLL is such a heterogeneous disease.
Neil
Do you know the significance of the mutation rate? His is 10.85%. Also, it says “the clonal IgVH gene belongs to VH3-23 family.” I’m not sure if that’s clinically relevant or not?
Also, another test result just came in and I have no idea what this one might mean. The test name is just “Chromosome, Blood.” It says, “RESULT: ABNORMAL KARYOTYPE WITH TRANSLOCATION (14;18) INTERPRETATION: Chromosome analysis revealed an abnormal clone with translocation between chromosomes 14q and 18q in 4/20 metaphase cells analyzed. The remaining sixteen cells presented a normal karyotype. The t(14;18) results in IGH::BCL2 gene rearrangement and is observed in 90% of follicular lymphoma and 20-30% of diffuse large B-cell lymphoma. Please expect the results of any other concurrent study in a separate report.” I have no idea what this result might mean?
This is another test of genes. Some patients have genetic abnormalities not commonly associated with CLL. This particular test is run to help distinguish CLL from a couple other related cancers/lymphomas, along with the Flow Cytometry results. A number of tests are generally all ordered at the same time. It's not super common for a CLL patient to have this particular translocation, but it's not unheard of.
I found a 2012 study talking about how the few CLL patients with this mutation (only 12) have a relatively young age at diagnosis (average at diagnosis is 70), mutated IVH, and half these people had Trisomy 12. This paper was an analysis of previous patients, and a discussion of the genetic abnormalities. I do not know how this might change a potential treatment, since this was written before the BTK's and Venclexta combos were available.
Now you are getting a taste of what I mean by CLL being heterogeneous! I was spared all this testing in Australia, because such testing is only done prior to beginning treatment (because it can change) - and only if it will influence treatment choice. Only 4 of the 20 metaphase cells (the 20% in the process of dividing which could be examined) were found with that translocation. Whether that becomes a dominant sub-clone depends on whether it provides a survival advantage for the CLL. It is treatments which most strongly drive sub-clone selection, where the sub-clones with more resistance to the treatment(s) are the only CLL cells left standing, so to speak.
With respect to his IGHV result, my report notes that "Cases with germline identity of between 97 and 97.9% are classified as borderline.", or in other words 3.0 to 3.7% mutated. So with a 10.85% difference from germline (from comparison with another body cell), there's no question that your bf falls into the IGHV mutated camp. I'm not aware of any significance for the VH3-23 family, though there is for other VH families.
Neil
Hi again karmacrepe,
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CLL is unpredictable, so each of us may experience different rates of progression, the genetic averages encompass a very broad range of patient prognostic results.
It may be useful to watch your bf's blood counts over the next 6 to 12 months, specifically the ALC (Absolute Lymphocyte Count) or Lymph #. While there is no magic number for starting treatment, the rate of rise will forecast whether he may need treatment in the next 2 years or may have 5 or more years of watch & wait.
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Len
A CLL diagnosis is not like "you have X infection, here is how X is treated". It's more like "you have heart disease". Where in the heart? Is it electrical, or a lesion? Or both? Are other vessels involved? How extensive is it? What symptoms are there? Depending on quite a number of variables, various treatment/combinations are done.
It's somewhat similar in CLL. Except CLL is rare, compared to heart disease, so there isn't yet a huge amount of information. So there isn't an "exact" thing to do.
Remember when looking at blood, there can be normal lymphocytes as well as defective ones. So the percentage is descriptive as to how many cells are defective in a sample of the bodys' blood. And also remember, CLL often accumulates because these defective lymphocytes don't die normally, not just because they are replicating like other cancer cells. So that complicates everything. IMO people are looking at percentages because it's something we can measure. It may or may not correlate with time to treatment, or a better outcome, but IMO no one can say with any certainty if and what any percentage "means" exactly. I think of it, in my case, as a snapshot of how much CLL infiltration I have, at that point in time. Since I have had successful treatments, I don't think it's had more significance that that, in my case at least. When I was first diagnosed, I had a very high percentage of defective cells on FISH. A repeat FISH a decade later, showed a lower percentage of lymphocyte cells having defects. Even though the absolute lymphocyte count was lower, initially.
Although there have been huge advances in knowledge as well as treatments this past decade, it's still a rare cancer. Doctors are still learning the various subtleties of what a particular test result might mean. I think the big takeaway right now, is the markers can help decide if one should avoid certain treatments that do not seem to work well on people with certain markers. As well as monitor people who may have a higher risk for Richters Transformation more closely.
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