My husband was diagnosed with IGA myeloma, t 4;14 abnormality, and hyperdiploidy. After alot of reading, I have found that the classifications with the t 4;14 are hypodiploid. Is it possible to be hyperdiploid with the t 4;14? Or do you feel the test was incorrect? Does it mean anything different to be hyperdiploid vs. hypodiploid with the t 4;14?
Thanks!
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Re: t 4;14
Hi ReaderTK,
This article discusses hyper and non hyperdiploid (aka hypodiploid) chromosome changes:
http://www.signalgenetics.com/publications/The_Prognostic_significance_of_Cytogenetics.pdf
The article states that in general, the hypodiploid group with t(4;14)(p16;q32) or t(14;16)(q32;q23) is considered a high- risk group, while the hyperdiploid patients with t(11;14)(q13;q32) are considered a better prognostic group.
NOTE however, that at the 2010 ASCO meeting bortezomib was shown to overcome the high risk prognosis of hypodiploid t(4:14) chromosomal change
http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=74&abstractID=48562
This article discusses hyper and non hyperdiploid (aka hypodiploid) chromosome changes:
http://www.signalgenetics.com/publications/The_Prognostic_significance_of_Cytogenetics.pdf
The article states that in general, the hypodiploid group with t(4;14)(p16;q32) or t(14;16)(q32;q23) is considered a high- risk group, while the hyperdiploid patients with t(11;14)(q13;q32) are considered a better prognostic group.
NOTE however, that at the 2010 ASCO meeting bortezomib was shown to overcome the high risk prognosis of hypodiploid t(4:14) chromosomal change
http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=74&abstractID=48562
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suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: t 4;14
Thank you for your response. I have read many of your questions and responses, and you seem very educated on this subject.
The article was informative, but still confusing because my husband is hyperdiploid AND t 4;14 chromosome abnormalitiy plus the t 14;32 abnormality. This article does not put t,hese two classifications together. You are either hyperdiploid OR hypodiploid with the t 4;14, so I am still confused about how he can be both and what is the significance of this?
One more question: his disease was refractory to Velcade, so does that mean the possiblility still exists that Velcade overcame the high risk status of his t 4;14?
Is t 4;14 the same translocation as t 14;32?
Thanks!!!!!!!
The article was informative, but still confusing because my husband is hyperdiploid AND t 4;14 chromosome abnormalitiy plus the t 14;32 abnormality. This article does not put t,hese two classifications together. You are either hyperdiploid OR hypodiploid with the t 4;14, so I am still confused about how he can be both and what is the significance of this?
One more question: his disease was refractory to Velcade, so does that mean the possiblility still exists that Velcade overcame the high risk status of his t 4;14?
Is t 4;14 the same translocation as t 14;32?
Thanks!!!!!!!
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Readertk - Name: Tiffany
- Who do you know with myeloma?: husband
- When were you/they diagnosed?: December 2009
- Age at diagnosis: 42
Re: t 4;14
Hi Readertk,
I'm sorry the article was unable to provide the information you were seeking.
Dr Shain answered a question somewhat similiar to the one you have here:
https://myelomabeacon.org/forum/monosomy-13-t-4-14-question-t724.html
Wishing you and your husband all the best.
I'm sorry the article was unable to provide the information you were seeking.
Dr Shain answered a question somewhat similiar to the one you have here:
https://myelomabeacon.org/forum/monosomy-13-t-4-14-question-t724.html
Wishing you and your husband all the best.
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suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: t 4;14
Is Dr Shain available to answer this question?
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Readertk - Name: Tiffany
- Who do you know with myeloma?: husband
- When were you/they diagnosed?: December 2009
- Age at diagnosis: 42
Re: t 4;14
Tiffany, the article suzirose posted states that you can be both hyperdiploid and have translocations. See the 2nd page, midway down on the right side, where it says:
"It should be pointed out that the generalized distinctions between the hyperdiploid and the hypodiploid groups are an oversimplification since the primary IGH translocations are also found in hyperdiploid multiple myeloma at a frequency of approximately 10% (31)."
I think that answers your original question.
"It should be pointed out that the generalized distinctions between the hyperdiploid and the hypodiploid groups are an oversimplification since the primary IGH translocations are also found in hyperdiploid multiple myeloma at a frequency of approximately 10% (31)."
I think that answers your original question.
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Chris
Re: t 4;14
Dear Readertk,
The 4;14 translocation can occur in hypodiploid and hyperdiploid scenarios. It should also be considered a high risk abnormality regardless of the other background abnormalities. The caveat here is that the prognostic value of the 4;14 translocation has not been dissected to the level that you would like with respect to your husband's situation (i.e. the specific situation of a 4;14 translocation AND hyperdiploidy).
The following article is a good representation of the fact that the more "high risk" abnormalities that are present, the harder the disease is to treat. The link is as follows:
http://www.ncbi.nlm.nih.gov/pubmed/21836613
This study addresses the issue of combinations of high risk cytogenetic abnormalities. It also demonstrates that the International stage adds prognostic value to the cytogenetic testing. Realize that these patients were treated with somewhat "older school" therapy, so the actual numbers regarding survival and durability of remissions do not necessarily apply to Revlimid (lenalidomide) and Velcade (bortezomib) treated patients.
As such, the fact that the only high risk lesion present in your husband's case is the (4;14) translocation is better than the presence of the 4;14 translocation and another high risk abnormality.
The (4;14) abnormality is not as powerful of a prognostic indicator in the modern era of myeloma therapy, especially with the use of Velcade and Revlimid. Patients are doing better!
I am a bit confused about the 14;32 translocation. The chromosome numbering does not go up to 32 (one set of 23 chromosomes from Mom, one set of 23 from Dad). The number 32 may refer to the "breakpoint" in chromosome 14 that was affected by the 4;14 translocation.
Lastly, the issue of Velcade refractoriness is important. I am always very cautious about deeming one's disease resistant to a particular drug class. What degree of response did your husband have to Velcade? Stable disease or minor response? Disease progression? How was the Velcade dosed and on what schedule? Were there other drugs that were used in combination with the Velcade? How did he tolerate it? The answers to these questions can have bearing on one's level of enthusiasm (or lack thereof) in using Velcade in the future for your husband.
Good luck and let us know how things go!
Pete V.
The 4;14 translocation can occur in hypodiploid and hyperdiploid scenarios. It should also be considered a high risk abnormality regardless of the other background abnormalities. The caveat here is that the prognostic value of the 4;14 translocation has not been dissected to the level that you would like with respect to your husband's situation (i.e. the specific situation of a 4;14 translocation AND hyperdiploidy).
The following article is a good representation of the fact that the more "high risk" abnormalities that are present, the harder the disease is to treat. The link is as follows:
http://www.ncbi.nlm.nih.gov/pubmed/21836613
This study addresses the issue of combinations of high risk cytogenetic abnormalities. It also demonstrates that the International stage adds prognostic value to the cytogenetic testing. Realize that these patients were treated with somewhat "older school" therapy, so the actual numbers regarding survival and durability of remissions do not necessarily apply to Revlimid (lenalidomide) and Velcade (bortezomib) treated patients.
As such, the fact that the only high risk lesion present in your husband's case is the (4;14) translocation is better than the presence of the 4;14 translocation and another high risk abnormality.
The (4;14) abnormality is not as powerful of a prognostic indicator in the modern era of myeloma therapy, especially with the use of Velcade and Revlimid. Patients are doing better!
I am a bit confused about the 14;32 translocation. The chromosome numbering does not go up to 32 (one set of 23 chromosomes from Mom, one set of 23 from Dad). The number 32 may refer to the "breakpoint" in chromosome 14 that was affected by the 4;14 translocation.
Lastly, the issue of Velcade refractoriness is important. I am always very cautious about deeming one's disease resistant to a particular drug class. What degree of response did your husband have to Velcade? Stable disease or minor response? Disease progression? How was the Velcade dosed and on what schedule? Were there other drugs that were used in combination with the Velcade? How did he tolerate it? The answers to these questions can have bearing on one's level of enthusiasm (or lack thereof) in using Velcade in the future for your husband.
Good luck and let us know how things go!
Pete V.
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Dr. Peter Voorhees - Name: Peter Voorhees, M.D.
Beacon Medical Advisor
Re: t 4;14
Thank you for the detailed reply.
Regarding the 14q32, my husband's bone marrow biopsy reads as follows:
Positive for 14q32 translocations in plasma. While most plasma cells present abnormalities involving the IGH 14q32 gene locus, only a minority have the one fusion, one red, green pattern.
What does this mean?
Also, you asked about resistance to Velcade. They gave him two cycles of Velcade dex. His M protein and IGA continued to increase. They then added Revlimid and the M protein and IGA dropped by 40 percent. He acheived a partial response by the end of five cycles (two with Velcade/dex and three more with Velcade/dex/Revlimid). We waited six weeks after last cycle to go into a stem cell transplant. In that six week period of time, his M protein and IGA levels increased by 50 percent in that short period of time. He acheived a VGPR after first tranplant and had a second transplant three months later. Also, VGPR.
Thanks for all of your help and information!!!
Regarding the 14q32, my husband's bone marrow biopsy reads as follows:
Positive for 14q32 translocations in plasma. While most plasma cells present abnormalities involving the IGH 14q32 gene locus, only a minority have the one fusion, one red, green pattern.
What does this mean?
Also, you asked about resistance to Velcade. They gave him two cycles of Velcade dex. His M protein and IGA continued to increase. They then added Revlimid and the M protein and IGA dropped by 40 percent. He acheived a partial response by the end of five cycles (two with Velcade/dex and three more with Velcade/dex/Revlimid). We waited six weeks after last cycle to go into a stem cell transplant. In that six week period of time, his M protein and IGA levels increased by 50 percent in that short period of time. He acheived a VGPR after first tranplant and had a second transplant three months later. Also, VGPR.
Thanks for all of your help and information!!!
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Readertk - Name: Tiffany
- Who do you know with myeloma?: husband
- When were you/they diagnosed?: December 2009
- Age at diagnosis: 42
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