[goldmine848]

FISH results - do they indicate high-risk disease?

by goldmine848 on Thu Jul 03, 2014 8:20 am

I have a question, presumably for those particularly knowledgeable about these issues.

I do not know if I am high risk since my first bone marrow biopsy did not produce aspirate and in subsequent ones no plasma cells were present.

However, I was reviewing my latest bone marrow biopsy report and I noticed a section entitled: "FISH -- Negative for multiple myeloma IGH complex rearrangements." Within that section, there is a sub-section entitled "Probe Set Detail:" that has references to t(14;20), t(4;14), t(11;14), and t(14;16). After each one there is the conclusion that the signal patterns are normal for various types of fusion.

I am interested in what this means and if it has any implications for whether my disease is high risk?

[Dan in Phoenix]

Re: FISH results - do they indicate high-risk disease?

by Dan in Phoenix on Thu Jul 03, 2014 2:34 pm

Hi Andrew,

I am not a physician, so maybe someone from the Beacon Staff can chime in, but to me it looks like your BMA was "non-diagnostic". They probably only got blood and no bone marrow in the "pulls".

If there were no plasma cells seen/present, then the FISH was done on normal cells, not myeloma cells, so you wouldn't expect any abnormalities. Quite honestly, I'm surprised they didn't QC the sample first and save the cost of running the test on a sample without myeloma cells present.

There are usually two step to a bone marrow biopsy; 1) A core of bone and marrow is extracted as solid tissue and 2) Liquid bone marrow aspirate is extracted. I believe the FISH is done on the aspirate cells smeared onto a glass slide.

Were plasma cells detected in your core biopsy? If so maybe, they can do FISH on these cells (I'm not sure if this is feasible and/or a validated assay). The aspirate is typically fresh cells, while the core might already be fixed in formaldehyde. Otherwise, another sample may need to be collected and hopefully this will contain plasma cells to analyze.

So the effect is that they never got disease cells to analyze and the results are meaningless.

I hope a good sample shows low risk disease and that you respond well to treatment.

Dan in Phoenix

PS- if they get a good sample next time, maybe ask them to do a proliferation index (PI) assay (probably Ki-67+ IHC), which tells the doctor how quickly your plasma cells are dividing. Slower disease (PI < ~0.5%) is often a good indicator and is different from cytogenetics picked up with FISH.

[goldmine848]

Re: FISH results - do they indicate high-risk disease?

by goldmine848 on Thu Jul 03, 2014 3:12 pm

Dan,

What you say makes sense since in prior BMB they did not do the FISH analysis since there were no plasma cells present.

[Ian]

Re: FISH results - do they indicate high-risk disease?

by Ian on Thu Jul 03, 2014 3:18 pm

Thanks for the useful information, Dan.

I have a quick question. Is the "proliferation index" you mention the same as the "plasma cell labeling index" (PLCI)? If it is, then If I'm not mistaken, the test is only available at a limited number of cancer centers, one of which is the Mayo Clinic. At least I think I saw that mentioned either here in the forum or some place else.

Just checked ... it was mentioned here in this forum. See Dr. Voorhees's posting here,

https://myelomabeacon.org/forum/plasma-cell-labeling-index-t1123.html

[Dan in Phoenix]

Re: FISH results - do they indicate high-risk disease?

by Dan in Phoenix on Thu Jul 03, 2014 4:19 pm

Yes Ian it is the same test.

I'm seen at both the Mayo-Scottsdale and UAMS so I'm lucky to really be getting seen at two leading institutions. Both institutions offer this test.

There's actually no reason this test can't be done at every center. Its an easy assay that just needs to be set up and validated.

It's important because slower growing disease takes longer to respond to therapy (mine took 3-4 months of CyBorD to reach complete response) but may also take longer to return once in remission. My last remission was 25 years.

I believe the more doctors know about each individual's disease the more tailored they can target the treatments for personalized medicine.

Hope this helps and my best best to you and all my fellow myeloma travelers.

Dan

[Dr. Ken Shain]

Re: FISH results - do they indicate high-risk disease?

by Dr. Ken Shain on Fri Jul 04, 2014 5:04 pm

Risk is an important aspect of our predicting outcomes for patients with multiple myeloma. This helps us also make decisions about what therapies to use and other critical aspects of disease management.

From myeloma-specific FISH (using CD138 enriched, or light chain localized, cells -- so only multiple myeloma cells) certain anomalies are associated with better or worse outcomes, as was stated in the original post. If there are no myeloma cells - in the case of a dry tap (no aspirate) - there cannot be testing on the multiple myeloma cells for FISH, cytogenetics, or GEP (MyPRS).

Established FISH anomalies that are regularly tested include:

• Hyperdiploidy (extra copies of odd numbered chromosomes; typically 3,5,7,9,11,15), t(11;14), t(6;14) are consider favorable
• Deletion chromosome 13 (del13) by itself has little significance
• Duplication of 1q21 (even though part of odd numbered chromosome), t(4;14), t(14;16), t(14;20) and deletion chromosome 17 (del17p) represent genetic anomalies with poor risk. The most significant tend to be t(4;14) and del17p. The use of Velcade (bortezomib)-containing therapy has improved the outcomes of t(4;14) patients significantly.

There are a number of published and ongoing studies trying to define new and/or better strategies to address patients with high risk risk disease.

The International Staging System (ISS) also has prognostic significance: Staging is based on beta-microglobulin and albumin -- two relatively simple labs tests, which divide patients into Stage I, II, or III. Those with ISS III having relatively poorer outcomes.

As has already been mentioned in this thread, there are other factors that have been linked to outcomes: PCLI (plasma cell labeling index), increased LDH, and elevated CRP, to name a couple.

In the end, is important to note that all of these staging or risk stratification systems put you in a box: patients that look like you. However, your disease is unique, and only time will truly tell.

Best of luck and I hope this helps.