Hi everyone. I was with my consultant haematologist today and my FISH test results show no abnormalities - I didn't think that this was even possible. On the face of it, its good news, but has anyone else had such a result?
I haven't been tested re mutated / unmutated status - seemingly not available easily here in Ireland. I hope to get that test done.
Given the level and progression rate of my lymph node load, including an enlarged spleen (but I've no idea how large) FCR is being recommended strongly. I'm thinking of seeking a second opinion from a CLL specialist but would love to hear from this community about this turn of events with my CLL.
Thanks in advance.
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KateEvaLen
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A FISH test showing no abnormalities just means that your particular variety of CLL is caused by a mutation not looked for by the FISH probes - they only look for a limited number. Such results are understandably confusing, given the summary of 'no abnormalities' or 'normal karyotype'. Hopefully you can be a bit more relaxed in knowing that well known bad abnormalities have been ruled out in your case.
If you are interested, here's the abstract of a 2007 European Hematology Association paper which looks at what is hidden in the 'normal' FISH results - what you and many of us (self included) face when given that arguably misleading information:
Prognostic Impact of Normal Karyotype in Chronic Lymphocytic Leukemia. Classical Cytogenetic Analysis or FISH?
Relevant snips:
"Cytogenetic analysis of chronic lymphocytic leukemia (CLL) patients, despite inherent technical limitations, has provided important information on disease biology and clinical outcome. FISH analysis is more sensitive; however, it only covers regions often involved in numerical or structural rearrangements and, therefore, does not allow assessment of the entire karyotype. (My emphasis) We evaluated 86 CLL patients with normal karyotype by interphase FISH and explored possible additional prognostic information. "
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The most frequent abnormality on FISH analysis in normal karyotype cases was del(13)(q14), which did not affect prognosis."
So in summary, CLL is a complex cancer with many causes (and which also makes it hard to cure). FISH only tests for some of the more common causes.
Getting the mutated / unmutated status reliably tested is difficult. It's not readily available in Australia either (other than via clinical trial centres).
Given FCR is being recommended strongly for you, getting a second opinion (presumably in England?) would be useful in confirming that's a good choice for you. Just think through and explore with your second opinion specialist what you can do if treatments other than FCR are deemed more suitable for you - but not available to you where you live. The most important outcome you want is confirmation that FCR should give you a long remission. I'm in somewhat the same situation as you, with FCR being recommended and the newer non-chemo treatments not available to me, so I know how you feel.
As usual Neil your response hits the mark. Thank you.
It's so difficult making treatment decisions especially the first treatment as the potential impact is clear for us all.
Yes - I'm Hoping to head to England as I want to be confident that my decision is the right decision. Will keep posting as this site really does help enormously, not least for your clear but also detailed knowledge about our Complex cancer.
First of all it's absolutely fantastic news that your FISH test has revealed none of the obvious adverse prognostic deletions. The importance of that can't be underestimated and I'd be delighted to hear it (I haven't yet had a FISH test).
In terms of mutation status, my understanding is that this can be obtained by the flow cytometry test which is carried out to establish the CLL diagnosis. Perhaps this has already been done? A result of CD38 negative in that test usually indicates that you're IGHV gene mutated which is positive with a longer time to first treatment.
The technical 'big guns' on here will be able to describe this to you in more exact detail than I.
However Kate, my feeling is that you have such incomplete information to work on or make decisions with. Why can't the doc tell you how enlarged the spleen is? Is it very painful and restricting your food intake? A scan would be quite definitive about enlargement. Mine was. I think the vagueness would make me want to seek a second specialist CLL opinion because starting treatment is such a crucial time and as I recall, you're fairly recently diagnosed. And your mutational status would become an important factor although everything you've said would make me very optimistic about that outcome.
How are your blood levels doing or is it the enlarged nodes and spleen that are driving his decision? And are they impacting on anything vital and impairing function? Do you feel it's time for treatment because I think being psychologically prepared is important too.
I'd seek a second opinion in your situation but your news today is brilliant!
Edit: I see Neil has answered with more technical detail so pleased about that!
I think I should clarify the situation with regards to CD38 and IGHV gene mutation status. I was recently interested to read that Prof Terry Hamblin found a rather poor correlation between the two, thinking like you that they were roughly equivalent (and I may even have mistakenly stated that in the past on this site). If you look at the scattergrams in Figures 1 and 3 in this letter to the editor of Blood by Prof. Terry Hamblin et al from way back in 2000, you'll see that whether they correlate or not depends on the patients and researchers:
There was indeed a great deal of interest by CLL researchers as to whether the easy to produce CD38 result via Flow Cytometry would be an adequate substitute for the harder to reliably reproduce IGHV gene mutation status test, but it seems the best we can say is per the paper: "V gene mutation status and CD38 expression are independent prognostic markers in B-CLL".
The letter concludes: "Why our results differ from those of Damle et al is a matter of speculation. We will be investigating whether CD38 expression is a constant over time in CLL." We now know that CD38 status can change over time with CLL, whereas IGHV gene mutation status is much more stable. Occasionally CLL patients report a change in their mutation status over time/after treatment, but the difficulties in reliably measuring it make it uncertain whether its the measurement accuracy or change over time that's responsible for the apparent change.
Interestingly the reference I provided to KateEvaLen above also mentions "CD38 expression and U-IGHV genes were associated with a shorter progression-free survival (PFS).", so you are quite right in highlighting that CLL patients should check out their CD38 status on their flow cytometry results. That's something everyone diagnosed with CLL should have access to, but I don't know if it always includes CD38 status.
Yes thanks for the clarification Neil and you're right in saying that the correlation has been mistakenly reported on the site in the past but clearly the understanding of CLL and its complexities is ever evolving.
It's a mistaken link my own haematologist has made to me.
It's interesting that many American CLL'ers appear to have awareness of their gene mutation status very quickly after diagnosis. Why is the IGHV mutation test more difficult to obtain elsewhere? It's something I've often wondered.
Re IGHV mutation test differences between the USA and elsewhere, I can only speculate that:
1) Flow Cytometry is easy to do accurately (and relatively cheaply) because it uses fluorescing antibodies that lock onto surface CD proteins on the CLL cell. Flow Cytometry is used to differentiate between different blood cancers - so there's a higher volume of testing.
2) To measure IGHV gene mutation status, you need to isolate the CLL IGHV gene from the RNA within the B-cells - both cancerous and normal (remembering that's metre long strands tightly coiled up into a helix structure within each cell's nucleus), and amplify enough of it to measure it reliably via DNA sequencing. That requires very careful quality control - difficulties getting consistent results across testing laboratories are well recognised. It's also a specific test for CLL patients, so there's less demand for it.
Presumably in countries with universal health care, the reluctance to pay for it out of the health budget and the lack of private demand results in little demand, with presumably much of that demand coming from patients enrolled in clinical trials.
So interesting that you should mention Clarient Labs in your post…in 2012, I was diagnosed with CLL and my FISH test indicated only a 13q deletion. I am also unmated. In 2014, after a biopsy on an enlarging lymph node a new FISH test showed an 11q (ATM) deletion, a 13q deletion and a 17p (TP53) deletion…quite a shock! My local hemo/onc sent me immediately to Dr. Coutre/Stanford University. Dr. Coutre said he had a feeling that these results just were not correct and had another FISH done at Stanford which confirmed only a 13q deletion. He said that Clarient Labs had made errors in the past so he was not comfortable accepting such a dramatic result in my case. I truly felt like I had dodged a bullet in my CLL journey! So I wanted to give a heads up regarding Clarient Labs. I give so much credit to my local CLL doctor for referring me to Dr. Coutre when things changed so dramatically…I now have two excellent doctors caring for me and I am so thankful to them both. Terry
I'm glad that worked out OK for you and you ended up with good CLL specialist - good thing you had an earlier FISH test that made you question your Clarient Lab result! I have no idea how Clarient Lab test result reliability compares; I just referenced their explanation of the IGVH test because they described in fairly easy to understand terms for what is quite a technical measurement.
My bloods are relatively good. All in normal range except for the ALC which is not too far out of that range at 5.48. But then I was diagnosed with SLL so not surprising.
You are right. It's the lymph nodes that are at issue. He's worried about internal organs - mentioned possibility of things like renal failure (which did give me pause for thought!) Spleen was not enlarged at my last CT scan in early June but was causing me discomfort by early Aug. Lymph nodes raised everywhere at this stage and not really waning at all now.
Well that puts a different complexion on things Kate particularly with such a marked spleen enlargement in two months.
Wishing you well with whatever you decide to do. It's such a defining moment for us when treatment is suggested and I can imagine how you are feeling about it. It's not something I'm looking forward to at all but pretty unavoidable it would seem. But I'd feel more confident with the FISH results you'd just been given.
Thanks NewDawn and I'll let you know how I'm getting on. Emotionally exhausted right now but in some strange way relieved as watch and wait is so difficult.
Your medic should easily be able to say how extended your spleen is by a simple physical exam I would suggest you ask that question if you wish to get the info.
My tests were simply to confirm FCR was the right treatment for me as with certain mutations,as you know, it is less effective. I guess,from what you say, that this is a similar situation for yourself?
If you haven't been given the choice of treatments I would say the medics are sure that FCR is the right one for you.
It doesn't hurt to ask the question though and if a second opinion would put your mind at rest then I'd go for it!
We are very similar I think, diagnostically speaking. I am 49 with SLL, "normal" karyotype FISH analysis and near-normal bloods. Our only difference is that my spleen is unaffected.
I sought a second opinion from Dr. Adrian Bloor at The Christie in Manchester. I didn't want to do it for fear that it may upset the original haematologist, but my employer insisted and I'm glad he did. They found a small percentage of Mantle Cell Lymphoma, which had not been tested for originally, and now we have as near to the complete picture as you can have. I have 30% bone marrow infiltration with about 10% of the 30% being Mantle Cell.
I was due to start FCR in August, before I transferred to The Christie, and it has taken this long to get the diagnosis right. I am medically in no hurry for treatment, but should start soon due to an axillary node the size of a tennis ball. Ironically, I'm still waiting fro the results of the last CT scan done yesterday.
Whilst in the first stages of diagnosis at The Christie, I was offered a chance to go on the FLAIR trial: FCR v Ibrutinib and Rituximab, but can't now go on it because of the Mantle Cell, but you might be able to, if that's what you would like.
Let me know what you think and I'll give you contact details, if you wish.
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