[angiebaldy]

Have MGUS, t(4;14) gone without treatment - is it possible?

by angiebaldy on Thu Jul 10, 2014 6:49 pm

I am perplexed, happy, and mad at the same time.

Two years ago, a paraprotein was found in my blood work and, after more tests and a bone marrow biopsy (BMB), I was diagnosed with IgA lambda MGUS with 8% involvement and the t(4;14) chromosomal abnormality.

Recently, I changed multiple myeloma specialists because I moved and needed one closer.

I know that abnormal plasma cells can be "patchy" and you can get different results from different BMB tests, but can the cytogenetics change?

My new doctor ordered a BMB and this one, per the nurse (I have not physically seen the results myself yet) is normal. The percentage of plasma cells is 5% with NO abnormal cytogenetics.

While I would love to do a happy dance, it confuses me. I am also angry if the first BMB was wrong! However, the first BMB was completed by my local oncologist I had before I moved, and it was sent to Genoptix for evaluation and then my old multiple myeloma specialist had the slides sent to him at Moffitt where their pathologist looked at the slides and confirmed 8% IgA lambda with t(4;14).

Can BMB change this drastically in 2 years?

What worries me is also this: When my new multiple myeloma specialist saw me for follow up of all my tests and BMB, he actually had someone else's lab results mixed up with mine. I did not realize this until I was checking out and looking through my labs while waiting, and there, right in the middle of mine, were someone else's labs. And my BMB was not ready yet (the doctor said he did not understand this because it should be and would look into it).

If my new BMB is correct, yeah!!

However I really have doubts and don't want to go through life thinking everything is ok when it isn't.

Any advice would be much appreciated!

[Multibilly]

Re: Have MGUS, t(4;14) gone without treatment - is it possib

by Multibilly on Thu Jul 10, 2014 9:19 pm

What did your latest serum tests tell you? Do you still have any parpaproteins in your serum, or are any of your FLCs or immunoglobluins out of whack? How did those numbers change from two years ago? That would be another important clue to look at.

IF you originally had a t(4;14) translocation, I believe it would be highly unlikely for that mutation just to disappear if you still have monoclonal proteins present (at least that is what I recall when I've read other posts asking if deleterious mutations can just disappear).

Note that a 5% plasma cell level is what a normal person without any monoclonal gammopathy would have, which is great. But note that you could have an 8% reading and a 5% reading on the same day if you took the samples in different spots ... so this variation over two years doesn't strike me as out of the ordinary (which you've already figured out). Assuming you still have a t(4;14) translocation, it is also possible that the BMB could miss catching those cells that have this translocation ... which might explain why the translocation isn't showing up.

Anyway, this is what I recall when these topics were discussed on other posts. Somebody else might have a different read on all this.

[angiebaldy]

Re: Have MGUS, t(4;14) gone without treatment - is it possib

by angiebaldy on Thu Jul 10, 2014 9:46 pm

Thanks for your response!

My numbers were about the same except my m-spike. It went from 0.9 to 0.42. I have been told in the past that the m-spike for me might not be a good way to monitor me because my paraprotein is in the beta region and it makes it harder to accurately measure. My IgA is and has always been in the mid 800s, and both of my other immunoglobulins are low at 474 for my IgG and 50 for my IgG. No Bence Jones protein. I am anemic, but it is iron deficiency so it doesn't count, thank goodness! My creatinine and calcium are normal and I have no lesions.

I guess that does make sense that if the cytogenetics aren't on all the aberrant plasma cells, then it is possible to obtain a specimen that is without the t(4;14). I guess this is why you are never really cured of it because it sort of hides in your body and may not be where the bone marrow biopsy is or where the other tests can see it.

[dnalex]

Re: Have MGUS, t(4;14) gone without treatment - is it possib

by dnalex on Thu Jul 10, 2014 10:58 pm

Hello,

I'm sorry for the confusion.

In light of everything, I would perhaps insist that another set of tests be run. Is that possible to do, or would insurance refuse?

[angiebaldy]

Re: Have MGUS, t(4;14) gone without treatment - is it possib

by angiebaldy on Fri Jul 11, 2014 1:31 pm

So I received a copy of my bone marrow biopsy today. There are no abnormal cytogenetics listed.

I have one more question though. On the FISH it does not specifically say that it was tested for t(4;14). What would be the test for the t(4;14). I don't even see FGFR3. I see CCND1,IGH but it is for t(11;14). Am I missing something. To me it appears as if they didn't test for it.

Thanks again in advance for any help!

[Multibilly]

Re: Have MGUS, t(4;14) gone without treatment - is it possib

by Multibilly on Fri Jul 11, 2014 2:04 pm

So, I have to believe that the lab used a standard set of probes intended for looking for mm-related mutations with your FISH test. The FISH test would ultimately look for the t(4;14) translocation.

If you look on your FISH report, you will probably find a section that references genes like "IGH" when it talks about the probes used on the test. IGH is a specific gene where the t(4;14) translocation can occur. I think the way it works is that the FISH test first looks for a rearrangement on this gene. If it finds one, then they will perform additional testing and analysis to look for the t(4;14) translocation, etc. Otherwise, they don't look for it. At least that's the way I think it works.

FISH tests are really hard for a layman to read and understand. After racking my brain over it for awhile when I first got my test results, I decided just to trust my doc's summary of it

[Dr. Adam Cohen]

Re: Have MGUS, t(4;14) gone without treatment - is it possib

by Dr. Adam Cohen on Sun Jul 13, 2014 9:37 am

Just to reiterate a couple of points that Multibilly correctly makes:

1. FISH testing for myeloma may differ between different pathology labs. Some run the FISH probes on unselected bone marrow cells, while others do a selection step to enrich for myeloma cells before running the FISH testing. So it can be hard sometimes to compare results between different pathology labs. In addition, some labs do a first step to look for any IgH translocation (IgH is on chromosome 14 and is the most common partner chromosome identified in myeloma translocations). Only if this first step is positive will they go back to identify the actual translocation (such as 4;14, 11;14, 14;16, etc.). If it's negative, they may not do the additional testing.
   
   
2. When there is only a low level of myeloma cells in the marrow, as in your case, it is possible to see the translocation in one marrow biopsy and not see it on the next. It likely is still present, just at a low level that wasn't picked up by the test.
   
   
3. The good news is that your M-spike and IgA levels are not increasing and you have no clinical evidence of progression to myeloma. So there's no indication to treat, just continue to monitor.

Hope this is helpful!

[angiebaldy]

Re: Have MGUS, t(4;14) gone without treatment - is it possib

by angiebaldy on Sun Jul 13, 2014 7:07 pm

Thank you for your reply Dr. Cohen. It was VERY helpful.

While I would love to believe that my t(4;14) has disappeared, it just didn't make sense to me without treatment. I also don't want to get too comfortable thinking it has gone and get blind sided by progression that should have been treated earlier.

I really thought this was probably what it was, but needed someone to explain it better. The patchiness of this disease can make a difference in the results. I am going to be vigilant about being monitored when I should so any progression can be dealt with quickly.

Thanks again everyone for your responses!