Hello,
I consider myself well informed about risk factors associated with progression of SMM to active disease, partly thanks to this forum, but I continue to be confused by the relevance of chromosome analysis and FISH in smoldering patients.
If you have a bone marrow biopsy and the cytogenetic results don't show any abnormal karyotype or rearrangements does this mean that the results are absolute and will not change?
I was just wondering how we smolderers can use this as an identifiable risk factor if cytogenetic abnormalities are subject to change and bone marrow monitoring isn't standard of care in following a smoldering patient? Are karyotypic changes an early event in the evolution of disease, and therefore reliable in determining progression from that one BMB we get at diagnosis or can they develop over time?
Are there myeloma patients without karyotypic instability?
Best
J
Forums
7 posts
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jhorner - Name: Magpie
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: 2013
- Age at diagnosis: 49
Re: Significance of cytogenetic results - smoldering myeloma
Hi J,
This is one of my previous posts:
"Can cytogenetics (chromosomal abnormalities) change?", Beacon forum discussion started February 23, 2014
So, if I can add a question to your post for others to consider: If cytogenetics can change, does early intervention create these changes, or potentially stop them?
This is one of my previous posts:
"Can cytogenetics (chromosomal abnormalities) change?", Beacon forum discussion started February 23, 2014
So, if I can add a question to your post for others to consider: If cytogenetics can change, does early intervention create these changes, or potentially stop them?
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gardengirl - Name: gardengirl
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Nov. 2013
- Age at diagnosis: 47
Re: Significance of cytogenetic results - smoldering myeloma
There are a few issues to address here. Cytogenetics / FISH are useful in prognosticating disease course to some degree, and likely will continue to become more predictive as it relates to which medications to use, or how aggressive to be with therapy (much of the latter remains to be better elucidated). The prognostic utility holds with both symptomatic and smoldering myeloma patients.
In terms of some of your questions ... As myeloma progresses over time, additional genetic abnormalities accumulate. These are not likely caused by treatment (though theoretically could be), but more relate to resistant clones that develop (much like using an antibiotic might give rise to a resistant germ over time).
We don't repeat bone marrow biopsies all the time in smoldering myeloma because subtle genetic changes absent a change in the pace of the disease (i.e., rising M-spike, or early end organ damage) would not result in any change in management. With significant clinical changes, repeat marrows are more often done.
These tests are not perfect. One might pick up a mutation once and not on repeat testing. We nonetheless place weight on these results because repeated studies validate them as important prognostic variables. Having 'normal' testing as a smoldering patient does not ensure abnormalities will not occur over time. Despite this lack of assurance, they are helpful.
Hope this was helpful. Living with smoldering myeloma can sometimes be very hard. Becoming an informed patient can help -- and you are clearly doing so.
In terms of some of your questions ... As myeloma progresses over time, additional genetic abnormalities accumulate. These are not likely caused by treatment (though theoretically could be), but more relate to resistant clones that develop (much like using an antibiotic might give rise to a resistant germ over time).
We don't repeat bone marrow biopsies all the time in smoldering myeloma because subtle genetic changes absent a change in the pace of the disease (i.e., rising M-spike, or early end organ damage) would not result in any change in management. With significant clinical changes, repeat marrows are more often done.
These tests are not perfect. One might pick up a mutation once and not on repeat testing. We nonetheless place weight on these results because repeated studies validate them as important prognostic variables. Having 'normal' testing as a smoldering patient does not ensure abnormalities will not occur over time. Despite this lack of assurance, they are helpful.
Hope this was helpful. Living with smoldering myeloma can sometimes be very hard. Becoming an informed patient can help -- and you are clearly doing so.
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Dr. James Hoffman - Name: James E. Hoffman, M.D.
Beacon Medical Advisor
Re: Significance of cytogenetic results - smoldering myeloma
Thank you gardengirl and Dr. Hoffman, this information was incredibly helpful. The bottom line is, regardless of risk stratification, treatment qualifiers don't change for smoldering myeloma, so risk isn't something we quantify in monitoring smoldering myeloma?
I am still curious if a patient with active multiple myeloma can have negative karyotypic results, or if all multiple myeloma patients have some of these instabilities?
Thank you so very much again!
Best
J
I am still curious if a patient with active multiple myeloma can have negative karyotypic results, or if all multiple myeloma patients have some of these instabilities?
Thank you so very much again!
Best
J
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jhorner - Name: Magpie
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: 2013
- Age at diagnosis: 49
Re: Significance of cytogenetic results - smoldering myeloma
All myeloma clones have 'genetic' abnormalities. In some, this can be found with a more cursory test -- the karyotype (or 'cytogenetics'). In others, they are only found with the more sensitive FISH testing. In a few, it requires more comprehensive, less commercially applied tests (e.g. genetic panels such as developed at UAMS / Arkansas) to identify the abnormalities.
Only some of these findings have validated utility (to predict disease course, or response to specific therapy, etc.) Others are less helpful in patient management.
Hope this answers your question.
Only some of these findings have validated utility (to predict disease course, or response to specific therapy, etc.) Others are less helpful in patient management.
Hope this answers your question.
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Dr. James Hoffman - Name: James E. Hoffman, M.D.
Beacon Medical Advisor
Re: Significance of cytogenetic results - smoldering myeloma
Thank you so much Dr. Hoffman! Your explanations are informative and concise, and I completely understand the logistics behind this testing.
Certain abnormalities assist with risk stratification as well as treatment strategy, so they are "looked for," while others are not. It doesn't mean that you don't have genetic instability, just that you don't have ones that are identifiable as making a difference.
I really appreciate your response!
Best,
J
Certain abnormalities assist with risk stratification as well as treatment strategy, so they are "looked for," while others are not. It doesn't mean that you don't have genetic instability, just that you don't have ones that are identifiable as making a difference.
I really appreciate your response!
Best,
J
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jhorner - Name: Magpie
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: 2013
- Age at diagnosis: 49
Re: Significance of cytogenetic results - smoldering myeloma
J,
I'm curious why you use terms like "karyotypic instability" and "genetic instability" almost like they mean the exact same thing as "chromosomal abnormality" and "genetic abnormality".
As I understand it, "instability" means a tendency to develop chromosomal or genetic abnormalities. I've also seen it used to describe situations where you have a lot such abnormalities, I assume because there has to be a tendency to have such abnormalities for a lot of them to develop.
But, just as an example, if a group of cancer cells has a single genetic abnormality, you wouldn't say those cells have "genetic instability". That's not something you could conclude from the presence of that one abnormality.
Sorry if this seems picky. I just want to make sure my understanding of these concepts is correct. Also, since these concepts are complex for most people here anyway, it's probably useful for a lot of people to make sure we're using the right terms to describe things.
I'm curious why you use terms like "karyotypic instability" and "genetic instability" almost like they mean the exact same thing as "chromosomal abnormality" and "genetic abnormality".
As I understand it, "instability" means a tendency to develop chromosomal or genetic abnormalities. I've also seen it used to describe situations where you have a lot such abnormalities, I assume because there has to be a tendency to have such abnormalities for a lot of them to develop.
But, just as an example, if a group of cancer cells has a single genetic abnormality, you wouldn't say those cells have "genetic instability". That's not something you could conclude from the presence of that one abnormality.
Sorry if this seems picky. I just want to make sure my understanding of these concepts is correct. Also, since these concepts are complex for most people here anyway, it's probably useful for a lot of people to make sure we're using the right terms to describe things.
7 posts
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