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Incomplete results on initial bone marrow biopsy

by kullybunnny1 on Tue Jan 27, 2015 9:50 am

I hate to bring yet another question on this subject, but here goes.

I'm IgG Kappa and was Stage III with 95% plasma involvement upon diagnosis. I immediately went into a 6 cycle VRD [Velcade, Revlimid, and dex] induction therapy and had an autologoust stem cell transplant (ASCT) within 9 months. My oncologist briefed me that's was classified high risk, but I was never afforded an opportunity to review my initial bone marrow biopsy (BMB) results.

While completing my fourth skeletal survey, the hospital lab offered online access to my reports. I happened to find the initial biopsy results and reviewed it. It stated that the FISH analysis could not be performed due to low cellularity and the flow cytometry was incomplete because the sample failed to yield any metaphase cells. This result lead to the cytogenetic / FISH studies being inconclusive.

I did find near the end of the results a flow cytometry analysis which showed a population of large abnormal cells comprising about 25% of the samples cells expressing "CD33", CD38+dim, CD45+dim, CD56+, CD79a+, CD117+dim, CD138+dim with intracytoplasmic kappa light chain restriction.

I've researched previous MB postings and other resources but can't get my head around how this connects to a high risk classification. Is there a link that explains this?

Thanks in advance for any thoughts!

Kully

kullybunnny1
Name: Kully
Who do you know with myeloma?: me
When were you/they diagnosed?: August 2013
Age at diagnosis: 48

Re: Incomplete results on initial bone marrow biopsy

by Multibilly on Tue Jan 27, 2015 10:56 am

Hey Kullybunny,

A doctor's use of the "high risk" classification can be quite varied. There simply is no standard for classifying high-risk multiple myeloma patients. I think you might be assuming that your doctor is using something like the Mayo "mSMART" criteria, which rely purely on genetics for risk classi­fi­ca­tion ... and mSMART is not a universal standard that all doctors utilize. But note that other doctors can also factor in things like high beta2 microglobulin, very high free light chain values, GEP results, etc, when using the high-risk classifier.

But as I look through your postings, it seems like you have had several BMBs. So, it could also be that one of your other BMBs revealed a high-risk genetic issue, but this particular BMB in question did not have sufficient material to do a good genetic analysis.

None of your test results are proprietary. You can ask the doctor's office or hospital for copies of any and all of your earlier BMB test results. All the test results are available to you under the law (assuming your are in the USA).
Last edited by Multibilly on Tue Jan 27, 2015 11:33 am, edited 1 time in total.

Multibilly
Name: Multibilly
Who do you know with myeloma?: Me
When were you/they diagnosed?: Smoldering, Nov, 2012

Re: Re: Incomplete results on initial bone marrow biopsy

by mrozdav on Tue Jan 27, 2015 11:10 am

I will venture to offer a response. You do not mention whether your tests indicated the type, if any, of mutations in your cancerous cells that were observed. My understanding is that, generally, the risk involved centers on identification of cellular mutations.

Another point: The literature indicates that flow cytometry often underestimates the quantity of cancerous cells, so if you are showing 25% and the flow cytometry test was less than satis­factory for the reasons stated, you may well have quite a bit more. I am sure that you will receive responses from others regarding these issues.

mrozdav

Re: Incomplete results on initial bone marrow biopsy

by Steve on Tue Jan 27, 2015 5:54 pm

KB,

Have you had any imaging done besides skeletal survey?

If not, you really should press your multiple myeloma doctor to establish a baseline with either MRI or PET/CT.

Best,

S.

Steve
Name: Steve
Who do you know with myeloma?: myself
When were you/they diagnosed?: December 2009
Age at diagnosis: 55

Re: Incomplete results on initial bone marrow biopsy

by kullybunnny1 on Tue Jan 27, 2015 6:22 pm

Thanks to all for the responses. Multibilly, I knew you'd have some great info and mrozdav, thanks for your thoughts too.

Steve, I've had a total of 3 MRIs, 3 CT scans, 2 DEXA, along with now 4 skeletal surveys.

My main concern is that I've never seen abnormality of chromosomes listed. Finding the mention of CD33 being expressed and searching for information, I've only found that it's a poor prognosis marker. My final biopsy listed a CD20 diagnostic marker.

Sorry to be so naive on this matter, but I'm trying to be a better advocate for my treatment plan.

Kully

kullybunnny1
Name: Kully
Who do you know with myeloma?: me
When were you/they diagnosed?: August 2013
Age at diagnosis: 48

Re: Incomplete results on initial bone marrow biopsy

by Multibilly on Tue Jan 27, 2015 6:41 pm

The "CD" designations (like CD38+) that you find on the BMB test results are not to be confused with chromosomal abnormalities. These CD designations are simply what are known as "clusters of differentiation" (or, alternatively, the cell's "immunophenotype"), which is just a fancy way of saying that the cell's surface has some specific markers. There are over 300 different clusters of differentiation. As an example, CD38+ is a common marker that is found predominantly on multiple myeloma cells (which is why certain drugs like some monoclonal antibodies are tuned to look for that specific CD38+ marker).

Healthy plasma cells typically have the following profiles of clusters of differentiation: CD19+, CD45+, CD20–, and CD56–.

Myeloma cells can have the following profiles of clusters of differentiation: CD56+, CD38+, CD138+, CD19-, CD45-, etc.

Some of the CD markers do have diagnostic relevance, and there are some articles discussing their potential prognostic impact. But, I don't recall doctors ever classifying the risk of a multiple myeloma patient based on the CD markers alone. Most of the current discussions around risk classification are more centered on one's cytogenetics (chromosomal abnormalities).

Multibilly
Name: Multibilly
Who do you know with myeloma?: Me
When were you/they diagnosed?: Smoldering, Nov, 2012

Re: Incomplete results on initial bone marrow biopsy

by JimNY on Tue Jan 27, 2015 8:26 pm

Hi Kully,

I'm hesitant to toss my hat into the ring when you've already gotten a lot of useful feedback, but there is an issue that Multibilly hinted at in his first posting that I wanted to explore further.

If I interpret correctly what you wrote in your first posting in this thread, you had 95 percent plasma cell involvement on your first bone marrow biopsy.

If that was the case, I find it very odd that your first bone marrow biopsy gave the results that you describe in your posting:

"FISH analysis could not be performed due to low cellularity and the flow cytom­etry was in­com­plete because the sample failed to yield any metaphase cells. This result lead to the cyto­genetic / FISH studies being inconclusive."

That statement basically says they couldn't find enough myeloma cells to do FISH or conventional cytogenetics. Yet, with 95 percent plasma cell involvement on your first biopsy, they should have been able to find enough cells to do those analyses.

Are you sure those results that you quoted are from your FIRST bone marrow biopsy?

JimNY

Re: Incomplete results on initial bone marrow biopsy

by kullybunnny1 on Tue Jan 27, 2015 9:50 pm

Jim,

Yes, I was at 95% plasma involved on my first bone marrow biopsy. When my 6 cycles of RVD and the second biopsy were completed, my oncologist briefed me on its results. He said, "And I made sure I had the best pathologist in the country to do this one!" I found this funny at the time but thought it was to alleviate any concerns I had. Like I mentioned in the earlier post, I'd wanted to see the results of all my biopsies but had only seen the results of the post-transplant biopsy.

As one of the Myeloma Beacon columnists wrote, the fog of treatment is slowly clearing and I'm gaining back my confidence to be an active member of my medical treatment team. Read­ing the results of that first biopsy only added to my confusion as to why I was classified high risk. There were some comments on the results that did not instill confidence, but I trust those professionals who have to deal with such a challenging disease.

Thanks for your thoughts, Jim!

Kully

kullybunnny1
Name: Kully
Who do you know with myeloma?: me
When were you/they diagnosed?: August 2013
Age at diagnosis: 48

Re: Incomplete results on initial bone marrow biopsy

by JimNY on Tue Jan 27, 2015 11:34 pm

Hi Kully,

Sorry, the question in my last posting may not have been clear. I wasn't really doubting you when you said that your plasma cell involvement was 95 percent on your first bone marrow biopsy.

When I asked "Are you sure those results that you quoted are from your FIRST bone marrow biopsy?", I was referring to these results:

"FISH analysis could not be performed due to low cellularity and the flow cytom­etry was in­com­plete because the sample failed to yield any metaphase cells. This result lead to the cyto­genetic / FISH studies being inconclusive."

Were those results really from your first bone marrow biopsy -- the one done when you were diagnosed?

JimNY

Re: Incomplete results on initial bone marrow biopsy

by Melanie on Wed Jan 28, 2015 12:02 am

This is a concern I have given my husband becoming refractory to RVD after his third cycle and then, while having an excellent response to the DR-PACE, his light chains rapidly rose again.

When I look at his cytogenic report, it states that the single culture established from this specimen failed to grow. Despite the culture and harvest attempt, no metaphase cells were available for analysis. So it makes me wonder if, in fact, there is a genetic risk factor that we do not know about which caused him to so quickly become refractory to the RVD.

Melanie
Name: Melanie
Who do you know with myeloma?: husband
When were you/they diagnosed?: July 2014
Age at diagnosis: 54

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