[blessthischick]

t(14;16) as indicator for high risk disease

by blessthischick on Wed Mar 12, 2014 8:33 pm

Hello Every1

Does anyone know about the above genetic abnormality -- t(14;16)? I also have a gain of chromosome 1q and deletion of 13q.

I am mgus/smoldering at the moment but saw the following article which has left me totally gutted and wondering if anyone can offer any hope in relation to this? 2 years is not long...and by the sounds of it they are not going to be a particularly happy clappy 2 years

http://www.medicalgrapevineasia.com/mg/2013/12/06/conquering-multiple-myeloma/

Would appreciate any help anyone can offer xx

[kjpoppit]

Re: t(14;16) as indicator for high risk disease

by kjpoppit on Wed Mar 12, 2014 8:58 pm

I have multiple myeloma with the t (4:14). I am doing CyBorD induction therapy right now and will be having a autologous transplant to be followed by an allogeneic transplant. It was explained the average length of remission time was 2 years if I just do the auto only. I think there is hope for a longer median lifespan than 2 years. There are advancements happening all the time.

Best wishes to you.

[Dr. Edward Libby]

Re: t(14;16) as indicator for high risk disease

by Dr. Edward Libby on Thu Mar 13, 2014 12:57 am

Hello from Seattle !

The first thing you need to be sure of is whether you have monoclonal gammopathy of undetermined significance (MGUS) OR smoldering (asymptomatic) multiple myeloma. They are two VERY different disorders. The risk of ever getting full blown myeloma requiring chemotherapy for a patient with MGUS is quite low at 1% per year. Smoldering myeloma has a risk of becoming symptomatic myeloma that requires treatment of 10% per year. You should clarify this critical distinction with your hematologist/oncologist.

The impact of cytogenetics on the rate of progression of smoldering (asymptomatic) myeloma is just beginning to be described.

[DanaH]

Re: t(14;16) as indicator for high risk disease

by DanaH on Fri Mar 14, 2014 12:08 am

What would be the necessary steps to take to clarify if someone is MGUS or smoldering, especially if someone is in that "grey/borderline" area of a just a "bit" over 10% plasma cells. What imaging diagnostics are important? What other tests would be important to rule in/rule out the "right/accurate" diagnosis and make this critical distinction?

Follow up monitoring would hinge upon the correct diagnosis as well, so it is important to get the right diagnosis, but not such an easy task it seems at times.

Thanks so much, Dr. Libby, for your insights. As always, they are very helpful.

Best,
Dana H.

[Dr. Edward Libby]

Re: t(14;16) as indicator for high risk disease

by Dr. Edward Libby on Fri Mar 14, 2014 1:33 am

If you have greater than or equal to 10% abnormal plasma cells in your bone marrow then by definition you have smoldering (asymptomatic) myeloma (SMM). It does not matter what the M-spike is you still meet the criteria for SMM with 10% or more. Of course you want to be certain that you do not have "CRAB" or else you need treatment.

Regarding the t(14;16) by FISH there are two recent studies looking how cytogenetics and FISH affect the rate of progression from SMM to symptomatic myeloma requiring treatment. Only one of them looked at the t(14;16) translocation. Rajkumar Leukemia (2013) 27, 1738–1744.

Only 11 out of 351 patients had the t(14;16) translocation but in this very small sample they found a median time to progression of 55 months. Besides cytogenetics and FISH other tools that can be used to estimate how long it may take for SMM to progress include serum free light chains and a bone marrow MRI.

[blessthischick]

Re: t(14;16) as indicator for high risk disease

by blessthischick on Fri Mar 14, 2014 4:19 am

Thank you Every1 for taking the time to reply to my post

I am sorry for the delay in getting back to you, the news of my cytogenetics has had a pretty dramatic effect on me plus I am in the UK so there is a time delay.

There has been a bit of wrangling as to whether I have MGUS or smoldering myeloma from a bone marrow biopsy (BMB) on 3rd of Sept last year. My haem cons thinks I had 9% plasma cells in my bone marrow (MGUS) and my cons in the NAC (they suspected AL amyloidosis this was ruled out on SAP scan) thought I had a little more so said I was in the smoldering myeloma category. I await another BMB in the next week.

I have a lamda excess SFLC ratio of 0.028 which my haem said would put me in the Intermediate risk category for progression. I do not have a paraprotien/M-spike, I make lambda light chains. I have no CRAB. I have a small amount of BJP in my urine, kidney function is fine. A skeletal survey and MRI spine ruled out any lytic lesions. My B-microglobulin is going to get done and also some flow cytometry will be sent which is a relatively new thing over here.

All this may help give more info as to my risk for progression to myeloma that needs treated (whether I am MGUS or SMM at the moment) but at the end of the day I have a set of cards that have been dealt already and these genetic abnormalities do not bode well once I progress and the outlook for me is very poor. To add to this, I am watched for signs of AL amyloidosis and a blood test called the serum nt probnp which indicates deposition of amyloid tissue in the heart has risen for the first time although still in normal limits.

I am 46 years old, an acute nurse for 28 years with a specialist qualification in palliative care plus I worked in a haematology ward for 3 years. My eyes are wide open and I need to find a way of coping with all this, I have a constant feeling of anxiety in my tummy/chest that won't go away. I am tired but find resting hard as I am on alert at all times. How do we find peace with all this?

Many thanks again Dr Libby, Dana & KJpoppit xx

[DanaH]

Re: t(14;16) as indicator for high risk disease

by DanaH on Fri Mar 14, 2014 5:05 pm

Hi there blessthischick,

Your response was wonderful -- providing all of your details and sharing with all of us is so very much appreciated. I am going to respond to your last thought --

"How do we find peace with all this?"

I surely don't have an answer for you, but I can validate how you feel as I am rowing in a similar boat. It does help to share with those who are in in similar situation.

All of the very best to you,
Dana H

Dr. Libby,
Thanks again for your insight and for responding so quickly. Support such as you offer is truly invaluable.
Dana

[batchusera]

Re: t(14;16) as indicator for high risk disease

by batchusera on Tue Feb 21, 2017 7:37 am

I just got the same thing and there is mixed information. What did you do for treatment? I have 15% right now with the t(14;16).

[PJD143]

Re: t(14;16) as indicator for high risk disease

by PJD143 on Fri Feb 24, 2017 10:57 pm

Hello,

My husband went today to a myeloma specialist at Dana Farber who explained the different factors regarding the progression of the translocation of 4,14.

My husband was not considered high risk until they found the 4,14 translocation.

These are his results and they have stayed within these numbers for 6 months.

Free Kappa - 189.9 (3.3 -19.4 mgL)
Free Lambda - 17.6 (5.7-26.3 mgL)
Free Kappa/Lambda - 10.78 (0.26-1.65) HIGHER SIDE

IgG 831 (700-1600 mg/dl)
IgA 454 (70-400 mg/dL) slightly above
IgM 60 (40-230 mg/dl)

PEP: No specific abnormalities seen on SPEP. Based on IFE (see separate report), monoclonal IgA kappa is detected in beta-2 region. Cannot quantify by densitometry. Continue following serum total IgA levels to monitor SPEP.

No CRAB
All other tests are normal.

According to the oncologist we were told that my husband had a lower smoldering multiple myeloma.

After today, going to a multiple myeloma specialist, his translocation does in fact have a higher risk of progression. She has considered my husband high-risk smoldering.

He will start a clinical trial with a combination of natural immuno pt inhibitor, Revlimid, and dexamethasone. (Sorry about spelling.)

She told us that they have had much success with this combination of drugs.

MY biggest concern is if in fact we get this to NOT progress to multiple myeloma, does he still have a greater chance of progression due to this T(4:14)?

Also regarding smoldering multiple myeloma. Do I understand this correctly. 50% over a period of 2 years. I am not sure about the percentages after this. After 5 years I believe it was suppose to decrease to a 2% chance of progression. However I believe this makes it 52% progression?
Or like MGUS it brings it down to 2% each year after once you get past the 5 year mark.

Any input would be greatly appreciated.

Thank you and good luck to all!

[Multibilly]

Re: t(14;16) as indicator for high risk disease

by Multibilly on Sat Feb 25, 2017 7:10 pm

Hi PJD,

I'm guessing if you are talking about a smoldering myeloma clinical trial at Dana Farber that has some history and is currently recruiting patients, then you are actually referring to this trial:

https://clinicaltrials.gov/ct2/show/NCT02903381?term=smoldering+dana+farber&rank=2

To better understand risk of progression in smoldering myeloma patients, see this thread:

https://myelomabeacon.org/forum/risk-of-progression-smoldering-myeloma-t4027.html

As far as your concern about whether t(4;14) will continue to pose a risk to disease progression during and after the clinical trial treatment, I think that will depend on whether the same clonal lines of myeloma cells with t(4;14) exist after the treatment. With myeloma, various mutations can come and go over time as the various clonal lines of cancer cells fight for dominance and the treatments knock down one or more of the clonal lines. So, I think that whether your t(4;14) translocation will continue to pose a risk will depend on whether that mutation is still around after the initial treatment. The way you would verify the presence of t(4;14) is through iFISH testing as part a bone marrow biopsy. But these are just ramblings from a layman. I would suggest discussing this with your specialist to get a more definitive answer.