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Understanding tetraploidy and FISH results

by Jbodnar on Sun Jun 08, 2014 10:56 am

Hi all,

Still trying to understand my FISH results. At the start of everything I was being bounced around from myeloma specialists and MDS specialists. Eventually having just a myeloma diagnosis. Hoping someone can help me make sense of these results.

Tests were done 4 months apart at different institutions with no treatment given.

First FISH evaluation:
FISH evaluation detected 4 copies of the FGFR3, MLL,and IGH genes and four copies of chromosomes 5,7,8,17 and 20 in 2.4% - 3% of the interphased cells examined.

Second FISH evaluation:
-13 abnormal
14q32(IGH sep) abnormal

Any thoughts would greatly be appreciated.

Thanks
Jen

Jbodnar
Name: Jen
Who do you know with myeloma?: Myself
When were you/they diagnosed?: 2012
Age at diagnosis: 45

Re: Understanding tetraploidy and FISH results

by Beacon Staff on Sun Jun 08, 2014 11:39 pm

Jen,

Can you clarify a bit more when exactly these tests were done?

We ask because in your posting above you say that the test results were done 4 months apart "with no treatment given".

However, in this earlier posting that you made, you said that you've been treated with Velcade and dexamethasone before and after a stem cell transplant.

So were these recent test results after you had stopped treatment with Velcade and dexamethasone post transplant? Or are these test results from before you started any treatment whatsoever?

Beacon Staff

Re: Understanding tetraploidy and FISH results

by Jbodnar on Mon Jun 09, 2014 10:28 am

Thank you for your response - sorry for any confusion.

The tests were done prior to having any treatment when I was first diagnosed as they were trying to determine the cause of my anemia - hbg round 6 and BMB showing 30% plasma cells. During the 7 months of trying to come up with a diagnosis I eventually developed pure red blood cell aplasia.

Anemia, M protein and % of plasma cells in the marrow improved after induction - 6 cycles VD. Post auto transplant my M protein and % of plasma cells in the marrow had increased but I was not anemic. I have since been on consolidation initially VD - 4 cycles and now RVD -4 cycles with no change - minimal M protein but it's still there. I have a BMB scheduled this week.

I am looking back at my original genetics to help guide me in a direction of either continue to push for a CR or be happy where I am and drop back to maintenance.

Any thoughts would be greatly appreciated
Thanks ,
Jen

Jbodnar
Name: Jen
Who do you know with myeloma?: Myself
When were you/they diagnosed?: 2012
Age at diagnosis: 45

Re: Understanding tetraploidy and FISH results

by Dr. Ken Shain on Tue Jun 10, 2014 8:35 am

A number of things that need to be considered between the FISH results.

The first involves how they were done. For multiple myeloma FISH, the FISH is done on isolated myeloma cells (either by light chain or by CD138-enrichment). As such, only the myeloma cells are being analyzed for molecular anomalies -- no other cells, including potential MDS cells, are contributing. In this case, if multiple myeloma was not suspected at the beginning, it was likely done on the complete marrow -- as would be done for MDS.

Second, different probe sets were ordered. Different institutions may order more or less probes as a standard (you stated you had been at myeloma specialists, so this should not be markedly different, but remains a possibility).

Third, testing error or variance -- one sample versus another.

Fourth, FISH is still based on a random sampling from a bone marrow aspirate. As we are learning every day, they is significant heterogeneity in this disease -- one sample may be different than the other.

Interpretation of the results also needs to be in context. Depending on the labs, there is a threshold of positive vs negative -- a percentage of FISH positive cells necessary per 100 or 200 that represents a true positive test.

Also, the disease can change over time - even without therapy (more of a hypothesis than a fact).

Lastly (at least in this post), the second marrow looks a bit incomplete -- without comment on the abnormalities in ch13 and igH e.g. deletion, loss, amplification, partner ... I would try to track down that information.

Were there any cytogenetic results (not always as helpful in multiple myeloma and not isolated, but can assist in some cases).

With residual disease, even in the face of what appear to be standard risk cytogenetics, I would argue in favor of maintenance therapy: Revlimid (daily or day 1-21/28). However, this decision is up to you and your treating MD. Good luck.

Dr. Ken Shain
Name: Ken Shain, M.D., Ph.D.
Beacon Medical Advisor


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