Hello and happy New Year to everyone.
I have a question related to my most recent bone marrow biopsy. This was my 12th bone marrow biopsy. My karyotype has always been normal. However, this time around it was not - stating:
Of 20 metaphases,18 were normal. And 2 had non clonal 7q deletions.
A 7q deletion is common in myeloid malignancies, particularly MDS and AML.
Since the definition of a clone requires 2 or more metaphases with the same abnormality the significance is unclear.
Clinical and pathological correlation is advised
Needless to say, I'm feeling a little uneasy with everything. I had an unusual presentation at diagnosis, hence all the biopsies. I had pure red blood cell aplasia and concerns with a myelodysplastic syndromes (MDS) component at diagnosis, which all improved with the myeloma treatment. We actually stayed clear of Revlimid for a time due to marrow concerns.
My marrow for the most part has been pretty good, typically just showing suspicion or persistent minimal involvement of the myeloma. However, this time around things are looking a little different. The marrow is now moderately hypo-cellular (70% - fat) with reactive erythroid hyperplasia. Erythroid elements are moderately increased and show megloblastic changes. The myeloid elements are moderately decreased and exhibit left shifted maturation.
I guess my concern is with the above changes in the karyotype coupled with the changes in the marrow, could this be the start of something, and should I be doing anything different with regards to monitoring things?
Thank you,
Hykergirl
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hykergirl - Name: Hykergirl
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: 2012
- Age at diagnosis: 45
Re: Karyotype now abnormal with 7q deletion
Hello Hykergirl,
I would also feel uneasy with the results of your recent analysis of your metaphases. I wonder why more metaphases were not analyzed. Is it not possible to reanalyze your bone marrow sample and thereby improve the statistics?
Before I was diagnosed with a kappa IgA myeloma with translocation t(4;14), I had been suffering with two lymphoproliferative disorders and concurrent anemia (transfusion dependent) and neutropenia. Initial tests also showed that I had MGUS. Additionally, my bone marrow was severely hypocellular with only 10% cellularity. I also suffered with symptoms suggesting autoimmune diseases. My bone marrow was a mess.
Fast forwarding ten years, my MGUS began to progress in a rapid fashion. In addition, my anemia began to get significantly worse. I became very fatigued and suffered from weakness and general malaise. A bone marrow biopsy was ordered and it was determined that I had 50% abnormal plasma cells in my marrow. I was diagnosed with multiple myeloma at that point.
In retrospect, I can say that the frequent testing of my blood (hemoglobin, white blood cells, M-spike, immunoglobulins, and free kappa and lambda concentrations) was an important part of the monitoring of the status of my blood disorder. These tests, along with my symptoms of increased fatigue, all pointed to a change in my condition.
My suggestion is to make sure that your regular testing is being done often enough to catch significant changes in your overall pattern. I cannot give a specific time frame as that is something that you and your doctor should decide upon. In my case, I started out with once a month testing, which increased to once every three weeks. Now that I am undergoing treatment, I am tested every week.
Best of luck to you,
Joe
I would also feel uneasy with the results of your recent analysis of your metaphases. I wonder why more metaphases were not analyzed. Is it not possible to reanalyze your bone marrow sample and thereby improve the statistics?
Before I was diagnosed with a kappa IgA myeloma with translocation t(4;14), I had been suffering with two lymphoproliferative disorders and concurrent anemia (transfusion dependent) and neutropenia. Initial tests also showed that I had MGUS. Additionally, my bone marrow was severely hypocellular with only 10% cellularity. I also suffered with symptoms suggesting autoimmune diseases. My bone marrow was a mess.
Fast forwarding ten years, my MGUS began to progress in a rapid fashion. In addition, my anemia began to get significantly worse. I became very fatigued and suffered from weakness and general malaise. A bone marrow biopsy was ordered and it was determined that I had 50% abnormal plasma cells in my marrow. I was diagnosed with multiple myeloma at that point.
In retrospect, I can say that the frequent testing of my blood (hemoglobin, white blood cells, M-spike, immunoglobulins, and free kappa and lambda concentrations) was an important part of the monitoring of the status of my blood disorder. These tests, along with my symptoms of increased fatigue, all pointed to a change in my condition.
My suggestion is to make sure that your regular testing is being done often enough to catch significant changes in your overall pattern. I cannot give a specific time frame as that is something that you and your doctor should decide upon. In my case, I started out with once a month testing, which increased to once every three weeks. Now that I am undergoing treatment, I am tested every week.
Best of luck to you,
Joe
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Wobbles - Name: Joe
- Who do you know with myeloma?: myself
- When were you/they diagnosed?: June 2016
- Age at diagnosis: 67
Re: Karyotype now abnormal with 7q deletion
Hi Hykergirl,
Your new chromosomal abnormality report may not necessarily indicate a change in your cytogenetics.
The new analysis looks like it was carried out using a testing procedure that is not "FISH", but what is known as "conventional chromosome analysis". You can tell that this was the case because of the low number of cells that were tested (20), and – most importantly – that the results refer to "metaphases".
Conventional chromosome analysis identifies chromosomal abnormalities by looking at a small number of cells, and examining cells when they are in the "metaphase" state, right before they divide into two new cells. Thus, conventional chromosome analysis is often called "metaphase cytogenetics".
A key difference between conventional cytogenetic testing and FISH cytogenetic testing is that conventional (metaphase) testing will tell you any and all major chromosomal deletions and gains that are present, regardless of the chromosomes involved. If you have a chromosome 18 deletion, for example, in some of your cells, it will be picked up by conventional cytogenetic testing, even though chromosome 18 deletions are rare in multiple myeloma patients.
This would not necessarily be the case with FISH chromosomal abnormality testing, because it involves the use of specific probes that are designed to detect specific chromosomal abnormalities. More importantly, only a limited number of FISH probes are typically used when testing cells from a myeloma patient. As you might imagine, the probes that are usually used in such cases are those that are likely to pick up chromosomal abnormalities that are considered important to a myeloma patient's response to treatment and prognosis.
What this means is that, in your previous FISH testing, you may not have had probes used that were designed to pick up deletions in your 7 chromosome. So this may not necessarily be a new development.
You will have to go back and look more closely at your previous testing to see if you had conventional (metaphase) testing done in the past and, if so, whether it found chromosome 7 deletions.
One final thing I should mention is that FISH testing usually involves examining many more cells than conventional (metaphase) testing. FISH testing often can involve testing of 100, or more, cells.
Good luck!
Your new chromosomal abnormality report may not necessarily indicate a change in your cytogenetics.
The new analysis looks like it was carried out using a testing procedure that is not "FISH", but what is known as "conventional chromosome analysis". You can tell that this was the case because of the low number of cells that were tested (20), and – most importantly – that the results refer to "metaphases".
Conventional chromosome analysis identifies chromosomal abnormalities by looking at a small number of cells, and examining cells when they are in the "metaphase" state, right before they divide into two new cells. Thus, conventional chromosome analysis is often called "metaphase cytogenetics".
A key difference between conventional cytogenetic testing and FISH cytogenetic testing is that conventional (metaphase) testing will tell you any and all major chromosomal deletions and gains that are present, regardless of the chromosomes involved. If you have a chromosome 18 deletion, for example, in some of your cells, it will be picked up by conventional cytogenetic testing, even though chromosome 18 deletions are rare in multiple myeloma patients.
This would not necessarily be the case with FISH chromosomal abnormality testing, because it involves the use of specific probes that are designed to detect specific chromosomal abnormalities. More importantly, only a limited number of FISH probes are typically used when testing cells from a myeloma patient. As you might imagine, the probes that are usually used in such cases are those that are likely to pick up chromosomal abnormalities that are considered important to a myeloma patient's response to treatment and prognosis.
What this means is that, in your previous FISH testing, you may not have had probes used that were designed to pick up deletions in your 7 chromosome. So this may not necessarily be a new development.
You will have to go back and look more closely at your previous testing to see if you had conventional (metaphase) testing done in the past and, if so, whether it found chromosome 7 deletions.
One final thing I should mention is that FISH testing usually involves examining many more cells than conventional (metaphase) testing. FISH testing often can involve testing of 100, or more, cells.
Good luck!
Re: Karyotype now abnormal with 7q deletion
Thank you Joe and Terry for your suggestions and explanations.
My karyotype (metaphase analysis) on my last 11 bone marrow biopsies has always shown 20 out of 20 cells examined being normal. Not sure why, Joe, but that always seems to be the number they've analyzed. This is the first time anything has ever been abnormal on the metaphase analysis.
My FISH is typically abnormal, showing a 13q deletion and a 14q 23 rearrangement when enough plasma cells are captured. As you had mentioned, Terry, I think they typically use probes more specific to the myeloma since that is what we are monitoring.
When being first diagnosed and they were "fishing "around to see what was going on, they did use different probes when doing the FISH analysis and some different abnormalities were found. I was told they were not sure of the significance of the findings since the percentages, although higher than the expected deviation, were low. I have them listed in my profile. One of the abnormalities mentioned on the report was that of the MLL gene which I've been told can play a part in AML and MDS.
Karyotype now showing 2 non clonal 7q deletions - was normal 11 times before
Recent changes in the bone marrow
WBC and neutrophil count consistently below normal - last 2 readings trending even lower then usual
Original FISH showing an over expression of the MLL gene
MDS component and pure red blood cell aplasia at diagnosis
Adding everything together – especially the changes in the karyotype with all the treatment, PET and CT scans – I can't help but wonder if something is in the process of transforming and if I am perhaps a little more at risk of developing a secondary primary malignancy due to my presentation at diagnosis.
I do remember being told, although both are significant, when an abnormality is found in the karyotype (metaphase analysis), it is more significant than when found doing a FISH analysis.
Sure hope a bad moon is not arising.
Thanks for your help,
Hykergirl
My karyotype (metaphase analysis) on my last 11 bone marrow biopsies has always shown 20 out of 20 cells examined being normal. Not sure why, Joe, but that always seems to be the number they've analyzed. This is the first time anything has ever been abnormal on the metaphase analysis.
My FISH is typically abnormal, showing a 13q deletion and a 14q 23 rearrangement when enough plasma cells are captured. As you had mentioned, Terry, I think they typically use probes more specific to the myeloma since that is what we are monitoring.
When being first diagnosed and they were "fishing "around to see what was going on, they did use different probes when doing the FISH analysis and some different abnormalities were found. I was told they were not sure of the significance of the findings since the percentages, although higher than the expected deviation, were low. I have them listed in my profile. One of the abnormalities mentioned on the report was that of the MLL gene which I've been told can play a part in AML and MDS.
Karyotype now showing 2 non clonal 7q deletions - was normal 11 times before
Recent changes in the bone marrow
WBC and neutrophil count consistently below normal - last 2 readings trending even lower then usual
Original FISH showing an over expression of the MLL gene
MDS component and pure red blood cell aplasia at diagnosis
Adding everything together – especially the changes in the karyotype with all the treatment, PET and CT scans – I can't help but wonder if something is in the process of transforming and if I am perhaps a little more at risk of developing a secondary primary malignancy due to my presentation at diagnosis.
I do remember being told, although both are significant, when an abnormality is found in the karyotype (metaphase analysis), it is more significant than when found doing a FISH analysis.
Sure hope a bad moon is not arising.
Thanks for your help,
Hykergirl
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hykergirl - Name: Hykergirl
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: 2012
- Age at diagnosis: 45
Re: Karyotype now abnormal with 7q deletion
Hi Hykergirl,
What does your oncologist say about these recent developments?
What does your oncologist say about these recent developments?
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Karyotype now abnormal with 7q deletion
Thanks for the clarification, Hykergirl.
I didn't realize that you had so much conventional cytogenetic testing done in the past. Your profile information only discusses previous FISH testing.
Although the phrase "normal karyotype" is typically used to describe the results of conventional cytogenetic testing, I've also seen FISH results summarized that way -- even if it's not strictly correct. That's why I wasn't sure if you always have had conventional cytogenetic testing done in addition to FISH testing.
In any case, I agree with Multibilly that it would be useful to know what your doctor thinks about this change.
Given that it appears to be an actual change, I agree that it suggests a change in your disease biology. Note, however, that conventional cytogenetics look at not just myeloma cells, but all bone marrow cells. That's different than FISH testing, which focuses on myeloma cells (in the case of someone with multiple myeloma).
What this means is that the change in your karyotype need not be related to your multiple myeloma. Instead, it may be related to the myelodysplastic syndrome you were diagnosed with at the same time as your myeloma diagnosis.
In any case, this definitely seems to be something that your doctor, who is the most familiar with your case, will best be able to interpret.
Just for the sake of reference, I found this useful post by Dr. Voorhees about conventional cytogenetics and FISH. Perhaps you'll find it helpful.
Good luck!
I didn't realize that you had so much conventional cytogenetic testing done in the past. Your profile information only discusses previous FISH testing.
Although the phrase "normal karyotype" is typically used to describe the results of conventional cytogenetic testing, I've also seen FISH results summarized that way -- even if it's not strictly correct. That's why I wasn't sure if you always have had conventional cytogenetic testing done in addition to FISH testing.
In any case, I agree with Multibilly that it would be useful to know what your doctor thinks about this change.
Given that it appears to be an actual change, I agree that it suggests a change in your disease biology. Note, however, that conventional cytogenetics look at not just myeloma cells, but all bone marrow cells. That's different than FISH testing, which focuses on myeloma cells (in the case of someone with multiple myeloma).
What this means is that the change in your karyotype need not be related to your multiple myeloma. Instead, it may be related to the myelodysplastic syndrome you were diagnosed with at the same time as your myeloma diagnosis.
In any case, this definitely seems to be something that your doctor, who is the most familiar with your case, will best be able to interpret.
Just for the sake of reference, I found this useful post by Dr. Voorhees about conventional cytogenetics and FISH. Perhaps you'll find it helpful.
Good luck!
Re: Karyotype now abnormal with 7q deletion
Hi Multibilly,
My myeloma specialist feels I do have something going on with regards to erythropoiesis at this point, and when I asked if it looked like things were transitioning towards something a little more involved, he said he really was not sure. He wants to pull another marrow, do additional genetic testing, and is setting us up with an myelodysplastic syndromes (MDS) specialist. I definitely agree with how he wants to move forward at this point, but must say I am feeling a bit anxious.
We were going to have the marrow repeated a week or so after we got the results back from the last marrow, but I hesitated, thinking it was too close to the last one. We decided to monitor things here with my local oncologist. I see him in a few weeks and will be moving forward with the repeated marrow and the MDS specialist in a few months when we go to see our myeloma specialist again.
Crazy how complex things can be.
Thanks for listening:)
And thanks for the helpful link Terry:)
Hykergirl
My myeloma specialist feels I do have something going on with regards to erythropoiesis at this point, and when I asked if it looked like things were transitioning towards something a little more involved, he said he really was not sure. He wants to pull another marrow, do additional genetic testing, and is setting us up with an myelodysplastic syndromes (MDS) specialist. I definitely agree with how he wants to move forward at this point, but must say I am feeling a bit anxious.
We were going to have the marrow repeated a week or so after we got the results back from the last marrow, but I hesitated, thinking it was too close to the last one. We decided to monitor things here with my local oncologist. I see him in a few weeks and will be moving forward with the repeated marrow and the MDS specialist in a few months when we go to see our myeloma specialist again.
Crazy how complex things can be.
Thanks for listening:)
And thanks for the helpful link Terry:)
Hykergirl
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hykergirl - Name: Hykergirl
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: 2012
- Age at diagnosis: 45
Re: Karyotype now abnormal with 7q deletion
I don't know if this is helpful or applies to your case, but I recently learned that apparently sometimes new mutations can pop up and then resolve themselves.
Last August, right as my husband was going to transplant, they found a new mutation (I think it may have been 7q, actually, but cannot recall for sure) that is associated with myeloproliferative cancers and postponed the transplant for two months with the intention of re-doing the bone marrow biopsy and seeing if the mutation was still there.
That sounded almost like magical thinking to me, but I did some reading that confirmed that our body can repair mutations that are just taking hold (i.e. not present in every cell of that type but only a percentage), and sure enough, the mutation had disappeared when they checked for it again. Which was a relief because he already has enough mutations that have no intention of disappearing.
It sounds like your docs are on top of it and you have plans to get another biopsy in a few months for them to compare, so I guess that, like all of us, all you can do is wait and see. I'm certainly not minimizing your concerns that your disease may be taking a different direction, but commiserating at what a complicated journey it takes the patients and family members on. I'm crossing my fingers that this doesn't turn out to be a new problem for you!
Last August, right as my husband was going to transplant, they found a new mutation (I think it may have been 7q, actually, but cannot recall for sure) that is associated with myeloproliferative cancers and postponed the transplant for two months with the intention of re-doing the bone marrow biopsy and seeing if the mutation was still there.
That sounded almost like magical thinking to me, but I did some reading that confirmed that our body can repair mutations that are just taking hold (i.e. not present in every cell of that type but only a percentage), and sure enough, the mutation had disappeared when they checked for it again. Which was a relief because he already has enough mutations that have no intention of disappearing.
It sounds like your docs are on top of it and you have plans to get another biopsy in a few months for them to compare, so I guess that, like all of us, all you can do is wait and see. I'm certainly not minimizing your concerns that your disease may be taking a different direction, but commiserating at what a complicated journey it takes the patients and family members on. I'm crossing my fingers that this doesn't turn out to be a new problem for you!
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mplsterrapin - Name: Ari
- Who do you know with myeloma?: Husband
- When were you/they diagnosed?: Fall 2015
- Age at diagnosis: 54
Re: Karyotype now abnormal with 7q deletion
Mplsterrapin,
Hello and thank you for your response. Excellent information to hear!! What a relief it must have been to receive the results that the mutation had resolved and he was cleared for the auto transplant.
Good luck with the transplant. Hope everything goes well. Positive thoughts to you and your family and all others on this journey.
Thanks for sharing,
Hykergirl
Hello and thank you for your response. Excellent information to hear!! What a relief it must have been to receive the results that the mutation had resolved and he was cleared for the auto transplant.
Good luck with the transplant. Hope everything goes well. Positive thoughts to you and your family and all others on this journey.
Thanks for sharing,
Hykergirl
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hykergirl - Name: Hykergirl
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: 2012
- Age at diagnosis: 45
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