I would love some opinions or feedback on my complex karyotype.
CYTOGENETICS:
KARYOTYPE:
55-60,X,-X,+1,add(1)(p12),t(1;5)(q32;q13),+2,+3,+4,+5,+6,+7,+9,
+11,+11,-13,+15,+15,-16,+17,+18,+19,add(20)(q11.2),+22[cp5]/
46,XX[16]
I have had chemo non-stop since February of 2014, and still my bone marrow biopsy is not below 20% plasma cells so I still can not go to SCT.
CyBorD (cyclophosphamide, Velcade, dexamethasone) worked for a while, then hit a plateau. Revlimid was added to the CyBorD, but now the Revlimid only seems to move counts when it is at the highest dose of 25 mg.
Other than neuropathy and feeling tired, I am taking the chemo pretty well but wonder how long I can keep this up.
I'm beginning to wonder if SCT will even be "worth it" with my karyotype. It seems many people relapse quickly after SCT.
I'm feeling discouraged and confused.
Forums
8 posts
• Page 1 of 1
-
Melpen - Name: Melissa
- Who do you know with myeloma?: myself
- When were you/they diagnosed?: Feb 5, 2014
- Age at diagnosis: 57
Re: Help understanding cytogenics and karyotype
Hello Melissa,
Your results are very complicated indeed, maybe you should go through them with a specialist.
We had a FISH done, even that was complicated to read and interpret, especially when some CD's (clusters of differentiation) are both expressed by normal cells but myeloma cells as well.
I would not base 100% on genetic results. For example, my partner Ian has one of the most aggressive light chain myelomas. The oncologist gave us 6 months without chemo!! The kappa light chains were well over 10 thousand!
When FISH was done, we already finished the first round of treatment with CTD (thalidomide, cyclophosphamide and dexamethasone). Ian reached a plateau as well, but shortly after, the disease was rising when still on the last cycle of thalidomide, to be honest.
At that point, we had a 1 month break. If I'm not wrong, Ian started cyclophosphamide, dex and Velcade after that. It knocked it down to something like 400 or 500.
We also went to Germany for total body hyperthermia. It worked great on Ian. It lowered the disease as much as Velcade, if not more, in terms of the light chains, but in terms of aggressiveness, not one bit. After 2 rounds of treatments and hyperthermia, it was still not stable, it kept growing.
With Ian still having hundreds of light chains in the blood, which clearly suggests symptomatic and persistant myeloma, we went for the stem cell transplant. The FISH test only found IgH rearrangement, but that might be because the treatment knocked most of the myeloma out and not many abnormalities were to be found, that doesn't mean Ian doesn't have them.
Melphalan destroyed the bone marrow; that why it's called myeloablation conditioning. It's obliterating your marrow, nothing left. Ian had his auto SCT in January. Till this day, his light chains are normalized, which indicates complete remission, but we need further tests to guarantee that. We hope it will last.
I would not rely on the plasma percentage 100%, Melissa, as some myeloma patients have diffuse and some focal myeloma. Ian's myeloma is focal so you have pockets and pockets of myeloma in the bone. It's not evenly spread. Imagine myeloma as dots on a paper. You have 1 sheet evenly spread all over with dots. All different regions on the paper look the same. And you have 1 sheet with pockets in certain places, followed by spaces that are clear of disease.
So a bone marrow biopsy in Ian's case is not representative because it s not a true reflection of the the disease, as it might come back normal, even when it's not. The doc drilled in a myeloma-free region.
As I said, I think you should not rely on biopsies 100% and see what your M-spike is (the monoclonal component in the blood). Whether it's a SPEP or sFLC so on. Your 20% might be very accurate, might be less or more. Nevertheless it's a test that should be done in conjunction with others.
If you are young and fit, you should consider SCT. Everyone with myeloma is considering it. It's not a cure, but it will keep the disease at bay. If you're lucky, for a long long time. If Ian had not gone through the SCT, I don't know where we would be. His disease never stopped growing, it was working round the clock. Suddenly we have hope that this would last, of course with proper care, good food, supplements and so on.
You might want to consider collecting for 2 SCTs and freeze the cells for a second transplant . The specialist managed to collect for 2 SCT for Ian, which is great. We wanted the cells frozen when they were still "naive" so to speak and were hit with only 2 different treatments. Myeloma cells have a memory, that is how they become resistant to treatment, and we didn't want to leave the second collection to be done at the time, because in the meanwhile the cells are becoming smarter and smarter and will only make our job more difficult.
If you have neuropathy problems, you can try Lyrica, but you need a prescription for that. It worked well for Ian. Natural products, reasonable priced, also work well: methylcobalamin (B12) , P-5-P (B6), Metafolin (B9) . These are all B-vitamins and help with neuropathy. If you are wondering about the different names they have, it's because this is the biologically active form and it's ready to be used by the body. If you take regular B12, the body will have to break it down into simpler substances like methylcolabamin for it to be readily available and to be used by the body.
Hope this helps. This has been our experiences since Ian was diagnosed in 2012.
Remember even if all odds are against you, you can still make it. We all respond in a different way. What doesn't work for someone might work great for you! I suppose we never know if it truly works for us, unless you take a risk. I am glad we did.
Keep hoping and smile.
Johanna
Your results are very complicated indeed, maybe you should go through them with a specialist.
We had a FISH done, even that was complicated to read and interpret, especially when some CD's (clusters of differentiation) are both expressed by normal cells but myeloma cells as well.
I would not base 100% on genetic results. For example, my partner Ian has one of the most aggressive light chain myelomas. The oncologist gave us 6 months without chemo!! The kappa light chains were well over 10 thousand!
When FISH was done, we already finished the first round of treatment with CTD (thalidomide, cyclophosphamide and dexamethasone). Ian reached a plateau as well, but shortly after, the disease was rising when still on the last cycle of thalidomide, to be honest.
At that point, we had a 1 month break. If I'm not wrong, Ian started cyclophosphamide, dex and Velcade after that. It knocked it down to something like 400 or 500.
We also went to Germany for total body hyperthermia. It worked great on Ian. It lowered the disease as much as Velcade, if not more, in terms of the light chains, but in terms of aggressiveness, not one bit. After 2 rounds of treatments and hyperthermia, it was still not stable, it kept growing.
With Ian still having hundreds of light chains in the blood, which clearly suggests symptomatic and persistant myeloma, we went for the stem cell transplant. The FISH test only found IgH rearrangement, but that might be because the treatment knocked most of the myeloma out and not many abnormalities were to be found, that doesn't mean Ian doesn't have them.
Melphalan destroyed the bone marrow; that why it's called myeloablation conditioning. It's obliterating your marrow, nothing left. Ian had his auto SCT in January. Till this day, his light chains are normalized, which indicates complete remission, but we need further tests to guarantee that. We hope it will last.
I would not rely on the plasma percentage 100%, Melissa, as some myeloma patients have diffuse and some focal myeloma. Ian's myeloma is focal so you have pockets and pockets of myeloma in the bone. It's not evenly spread. Imagine myeloma as dots on a paper. You have 1 sheet evenly spread all over with dots. All different regions on the paper look the same. And you have 1 sheet with pockets in certain places, followed by spaces that are clear of disease.
So a bone marrow biopsy in Ian's case is not representative because it s not a true reflection of the the disease, as it might come back normal, even when it's not. The doc drilled in a myeloma-free region.
As I said, I think you should not rely on biopsies 100% and see what your M-spike is (the monoclonal component in the blood). Whether it's a SPEP or sFLC so on. Your 20% might be very accurate, might be less or more. Nevertheless it's a test that should be done in conjunction with others.
If you are young and fit, you should consider SCT. Everyone with myeloma is considering it. It's not a cure, but it will keep the disease at bay. If you're lucky, for a long long time. If Ian had not gone through the SCT, I don't know where we would be. His disease never stopped growing, it was working round the clock. Suddenly we have hope that this would last, of course with proper care, good food, supplements and so on.
You might want to consider collecting for 2 SCTs and freeze the cells for a second transplant . The specialist managed to collect for 2 SCT for Ian, which is great. We wanted the cells frozen when they were still "naive" so to speak and were hit with only 2 different treatments. Myeloma cells have a memory, that is how they become resistant to treatment, and we didn't want to leave the second collection to be done at the time, because in the meanwhile the cells are becoming smarter and smarter and will only make our job more difficult.
If you have neuropathy problems, you can try Lyrica, but you need a prescription for that. It worked well for Ian. Natural products, reasonable priced, also work well: methylcobalamin (B12) , P-5-P (B6), Metafolin (B9) . These are all B-vitamins and help with neuropathy. If you are wondering about the different names they have, it's because this is the biologically active form and it's ready to be used by the body. If you take regular B12, the body will have to break it down into simpler substances like methylcolabamin for it to be readily available and to be used by the body.
Hope this helps. This has been our experiences since Ian was diagnosed in 2012.
Remember even if all odds are against you, you can still make it. We all respond in a different way. What doesn't work for someone might work great for you! I suppose we never know if it truly works for us, unless you take a risk. I am glad we did.
Keep hoping and smile.
Johanna
-
johanna - Name: Joanna
- Who do you know with myeloma?: Husband
- When were you/they diagnosed?: august 2012
- Age at diagnosis: 60
Re: Help understanding cytogenics and karyotype
Thank you for your extensive reply. It feels reassuring to know there is someone out there who cares enough to read a post and reply. Gives me the courage and faith to keep-on keeping-on
As for blood labs:
PEP is now 11% 675 mg/dl and was at 37% 3000 mg/dl in February
Free kappa is 51.0 and was 8800 in February
IgG is 913 and was at 3218 in February
As you can see, I have made great progress since last winter but it has not been a straight decline down. Some months counts would even inch up or not move much at all. I guess I am getting antsy as I thought I'd be going to SCT by now. Even the docs thought I'd be ready by autumn but, based on the bone marrow biopsy a few weeks ago, the docs say not yet. Even my blood counts are moving slow now, but with the Revlimid increased again to 25mg it should move things along. However I get confused when I read reports claiming that patients with complex cytogenics relapse quickly after stem cell. Then I wonder if it will all be for naught heading to stem cell
I understand what you are saying about the bone marrow. You could drill in two different areas and get two different counts.
As for the neuropathy, I just recently began Lyrica (pregabalin). You are right, it definitely helps along with the B-vitamins. I am so glad I am getting some relief as it makes the whole chemo experience way more tolerable, but of course the fatigue is still bothersome.
My doc did say she would harvest for two transplants.
God bless you and Ian. I hope he remains in remission and you two continue to enjoy life to the fullest for many long years yet to come
As for blood labs:
PEP is now 11% 675 mg/dl and was at 37% 3000 mg/dl in February
Free kappa is 51.0 and was 8800 in February
IgG is 913 and was at 3218 in February
As you can see, I have made great progress since last winter but it has not been a straight decline down. Some months counts would even inch up or not move much at all. I guess I am getting antsy as I thought I'd be going to SCT by now. Even the docs thought I'd be ready by autumn but, based on the bone marrow biopsy a few weeks ago, the docs say not yet. Even my blood counts are moving slow now, but with the Revlimid increased again to 25mg it should move things along. However I get confused when I read reports claiming that patients with complex cytogenics relapse quickly after stem cell. Then I wonder if it will all be for naught heading to stem cell
I understand what you are saying about the bone marrow. You could drill in two different areas and get two different counts.
As for the neuropathy, I just recently began Lyrica (pregabalin). You are right, it definitely helps along with the B-vitamins. I am so glad I am getting some relief as it makes the whole chemo experience way more tolerable, but of course the fatigue is still bothersome.
My doc did say she would harvest for two transplants.
God bless you and Ian. I hope he remains in remission and you two continue to enjoy life to the fullest for many long years yet to come
-
Melpen - Name: Melissa
- Who do you know with myeloma?: myself
- When were you/they diagnosed?: Feb 5, 2014
- Age at diagnosis: 57
Re: Help understanding cytogenics and karyotype
Hello Melissa,
So I take it you have IgG kappa type.
You mentioned your counts are going down rather slowly. Now I am no doctor and don't intend to (probably a doc will need to agree with this), but from all that I read, it seems at least in light chain myeloma (I think it applies to others as well, not sure) a massive rapid reduction of light chains is a very bad prognostic factor for myeloma patients.
I'm sure I read that a rapid response in treatment and drastic reduction of the monoclonal component with any type of response (complete response, stable response, partial response, etc.) is usually not sustainable, and the disease returns quicker than expected. So maybe that's what you need. A slow reduction that keeps dropping and dropping and hopefully stays there.
Ian's stem cell transplant was successful so far, and I want to add a few things that might help you.
To start with, Ian's last therapy line (VCD + hyperthermia) knocked it down to about 400-500 light chains. This was about November or October I would say and was still growing! The oncologist said the transplant will be done in January, and as long as its not above 1000, he's not bothered!
I suspect by the time the collection was made and melphalan given he must have had figures close to 1000. But we still did it.
In my mind, this is completely normal. For me, it doesn't make any sense to get numbers closer and closer to normal through conventional chemo and then administer the melphalan, because the chemo will have nothing to kill then. Does this make any sense to you?
Meplhalan is given anyway in massive doses to completely destroy the bone marrow so it doesn't matter if its 900 or 240, it will still destroy everything. And meplahan is not given with "consideration" for your well being like the chemo, i.e. that if you get neuropathy or sickness, they will lower it. Melphalan is given at such a high dose that is just about kill you. The stem cells will bring you back to life. So from my point of view, melphalan can easily do the job even if the numbers are higher.
As for treatments, Ian had Velcade and thalidomide so far and steroids. So that is why we were pushing for stem cell collection. In my view, the cells evolve all the time, they learn from how your body reacts and fights and they resist it and they do the same with chemo. They learn how to avoid and hide from it, so the sooner you harvest the better I would think. If you had 3, 4 prior lines of treatments before the transplant, the cells have already been exposed to it and might not take the bait if you know what I mean.
If you do the transplant and the disease comes back, you will have a much better chance with drugs that have not been used before. So it helps when cells have been preserved in frozen state and have not been touched by much chemo.
Another thing: If you go through the transplant and you want to collect for second (I think you should really consider it), they will give you GCSF, a growth factor to stimulate stem cell overproduction. They will overspill in your blood and be collected from there.
The GCSF injections can be quite a big disappointment for some people. We all respond differently to chemo so its only logical we respond the same to growth factors for stem cells. If this is the case, ask your doc about a new type of drug that works very well in people who have poor responses to GCSF. It is called Mozobil or plerixafor. It's about 5,ooo grand a pop, but if you need, it they will have give it to you!
If you get poor figures in the first couple of days, they will drop the second collection and only go for one if there is no further plan. Ian had only GCSF for 1 or 2 days, poor response to it, then he finally got the Mozobil (6 shots in 3 days), and the response was great so they collected for 2 in 3 days. I think with over 5 hours a day on the machine, which was much longer than usual, but we made it clear we were desperate so they were very responsive and kind.
I don't know about genetic abnormalities and quick relapses, but I'm quite sure there are a few people that have made it and beat the studies and the odds they had and their response was beyond expectation so don't put yourself down. This disease is so cruel and ruthless that we can't afford to take too much time and postpone things. And it's certainly a disease that is so so smart and we have to throw everything at it!
Nobody can tell you when you will relapse after the transplant, or when Ian will relapse, but we have to stay positive, mind over body. It's very important not to have a defeated attitude. Go for it.
I wish you the best, let me know how your transplant goes. All the best!
Kind regards, Joanna and Ian
So I take it you have IgG kappa type.
You mentioned your counts are going down rather slowly. Now I am no doctor and don't intend to (probably a doc will need to agree with this), but from all that I read, it seems at least in light chain myeloma (I think it applies to others as well, not sure) a massive rapid reduction of light chains is a very bad prognostic factor for myeloma patients.
I'm sure I read that a rapid response in treatment and drastic reduction of the monoclonal component with any type of response (complete response, stable response, partial response, etc.) is usually not sustainable, and the disease returns quicker than expected. So maybe that's what you need. A slow reduction that keeps dropping and dropping and hopefully stays there.
Ian's stem cell transplant was successful so far, and I want to add a few things that might help you.
To start with, Ian's last therapy line (VCD + hyperthermia) knocked it down to about 400-500 light chains. This was about November or October I would say and was still growing! The oncologist said the transplant will be done in January, and as long as its not above 1000, he's not bothered!
I suspect by the time the collection was made and melphalan given he must have had figures close to 1000. But we still did it.
In my mind, this is completely normal. For me, it doesn't make any sense to get numbers closer and closer to normal through conventional chemo and then administer the melphalan, because the chemo will have nothing to kill then. Does this make any sense to you?
Meplhalan is given anyway in massive doses to completely destroy the bone marrow so it doesn't matter if its 900 or 240, it will still destroy everything. And meplahan is not given with "consideration" for your well being like the chemo, i.e. that if you get neuropathy or sickness, they will lower it. Melphalan is given at such a high dose that is just about kill you. The stem cells will bring you back to life. So from my point of view, melphalan can easily do the job even if the numbers are higher.
As for treatments, Ian had Velcade and thalidomide so far and steroids. So that is why we were pushing for stem cell collection. In my view, the cells evolve all the time, they learn from how your body reacts and fights and they resist it and they do the same with chemo. They learn how to avoid and hide from it, so the sooner you harvest the better I would think. If you had 3, 4 prior lines of treatments before the transplant, the cells have already been exposed to it and might not take the bait if you know what I mean.
If you do the transplant and the disease comes back, you will have a much better chance with drugs that have not been used before. So it helps when cells have been preserved in frozen state and have not been touched by much chemo.
Another thing: If you go through the transplant and you want to collect for second (I think you should really consider it), they will give you GCSF, a growth factor to stimulate stem cell overproduction. They will overspill in your blood and be collected from there.
The GCSF injections can be quite a big disappointment for some people. We all respond differently to chemo so its only logical we respond the same to growth factors for stem cells. If this is the case, ask your doc about a new type of drug that works very well in people who have poor responses to GCSF. It is called Mozobil or plerixafor. It's about 5,ooo grand a pop, but if you need, it they will have give it to you!
If you get poor figures in the first couple of days, they will drop the second collection and only go for one if there is no further plan. Ian had only GCSF for 1 or 2 days, poor response to it, then he finally got the Mozobil (6 shots in 3 days), and the response was great so they collected for 2 in 3 days. I think with over 5 hours a day on the machine, which was much longer than usual, but we made it clear we were desperate so they were very responsive and kind.
I don't know about genetic abnormalities and quick relapses, but I'm quite sure there are a few people that have made it and beat the studies and the odds they had and their response was beyond expectation so don't put yourself down. This disease is so cruel and ruthless that we can't afford to take too much time and postpone things. And it's certainly a disease that is so so smart and we have to throw everything at it!
Nobody can tell you when you will relapse after the transplant, or when Ian will relapse, but we have to stay positive, mind over body. It's very important not to have a defeated attitude. Go for it.
I wish you the best, let me know how your transplant goes. All the best!
Kind regards, Joanna and Ian
-
johanna - Name: Joanna
- Who do you know with myeloma?: Husband
- When were you/they diagnosed?: august 2012
- Age at diagnosis: 60
Re: Help understanding cytogenics and karyotype
Hi Melissa,
Johanna has given you a lot of good information and advice.
Just to add a bit more. Maybe you already know this, but just in case you don't...
The different chemo agents that you've been getting use different mechanisms to attack myeloma cells. Cyclophosphamide (Cytoxan) and melphalan are both alkylating agents, Velcade is a proteasome inhibitor, and Revlimid is an immunomodulatory agent. You'll also hear drugs like Velcade and Revlimid (non-alkylating agents) referred to as "novel" agents or "targeted" agents, because they target more specific types of cells to attack, as compared to alkylating agents, which attack all fast-growing cells.
Myeloma is a "diverse" disease in the sense that even within an individual person, there are genetic differences between the myeloma cells in that one person. So attacking myeloma from different angles (with these different types of agents) seems to work best.
No single agent, not even high dose melphalan, is successful at killing all your myeloma cells. And, unfortunately, not even in any combination yet. But treatment outcomes are improving rapidly, both for standard risk patients and high risk patients.
In general, myeloma specialists want to drive the myeloma tumor burden as low as possible before proceeding with the auto SCT. You can think of that as getting as much benefit as possible from the targeted agents before blasting what remains with the high-dose melphalan. I've read some figures about what kind of response myeloma specialists want to see as a minimum response before doing the SCT, but I can't put my hands on any references for that right now.
In my case, when I started VRD induction treatment, my m-spike was 2.0. It got down to 0.4 before the SCT, so that was only a partial remission. The SCT did not change the m-spike much, but further VRD consolidation treatment after the SCT and Revlimid maintenance, which I'm still on, have gotten me into CR and MRD-negative.
So do not get discouraged! Keep on going and do what needs to be done. That's my motto.
Johanna has given you a lot of good information and advice.
Just to add a bit more. Maybe you already know this, but just in case you don't...
The different chemo agents that you've been getting use different mechanisms to attack myeloma cells. Cyclophosphamide (Cytoxan) and melphalan are both alkylating agents, Velcade is a proteasome inhibitor, and Revlimid is an immunomodulatory agent. You'll also hear drugs like Velcade and Revlimid (non-alkylating agents) referred to as "novel" agents or "targeted" agents, because they target more specific types of cells to attack, as compared to alkylating agents, which attack all fast-growing cells.
Myeloma is a "diverse" disease in the sense that even within an individual person, there are genetic differences between the myeloma cells in that one person. So attacking myeloma from different angles (with these different types of agents) seems to work best.
No single agent, not even high dose melphalan, is successful at killing all your myeloma cells. And, unfortunately, not even in any combination yet. But treatment outcomes are improving rapidly, both for standard risk patients and high risk patients.
In general, myeloma specialists want to drive the myeloma tumor burden as low as possible before proceeding with the auto SCT. You can think of that as getting as much benefit as possible from the targeted agents before blasting what remains with the high-dose melphalan. I've read some figures about what kind of response myeloma specialists want to see as a minimum response before doing the SCT, but I can't put my hands on any references for that right now.
In my case, when I started VRD induction treatment, my m-spike was 2.0. It got down to 0.4 before the SCT, so that was only a partial remission. The SCT did not change the m-spike much, but further VRD consolidation treatment after the SCT and Revlimid maintenance, which I'm still on, have gotten me into CR and MRD-negative.
So do not get discouraged! Keep on going and do what needs to be done. That's my motto.
-
mikeb - Name: mikeb
- Who do you know with myeloma?: self
- When were you/they diagnosed?: 2009 (MGUS at that time)
- Age at diagnosis: 55
Re: Help understanding cytogenics and karyotype
Dear Melissa,
You have hyperdiploid myeloma, meaning that you have an extra number of chromosomes in your myeloma cells. This is generally considered good. However, you do have a couple of intermediate / higher risk features on your cytogenetic testing, as well.
Specifically, you have a missing chromosome 13. This is not considered a risk factor when detected by FISH testing but is normal on conventional cytogenetic testing. In your case, it was picked up on conventional cytogenetic testing, so it would be considered an intermediate risk feature by Mayo Clinic criteria.
You also have an extra copy of chromosome 1. This is also considered a higher risk feature.
As far as what to do with this information, I would say that it will be important to consider the transplant option in first remission, as well as post-transplant consolidation and maintenance strategies, much in the same vein as mikeb on this posting.
On the positive side of things, it looks like you have had a very nice response to therapy based on blood and urine test results! As such, even if the marrow burden of plasma cells is higher than preferred, I think the transplant option should be on the table for discussion in light of your response to therapy (unless there are nuances in your case that cannot be gleaned from this posting). Upon recovery, the disease status could be re-evaluated and the pros / cons of post-transplant consolidation and/or maintenance therapy be discussed.
I hope this helps. Best wishes and take care!
Pete V.
You have hyperdiploid myeloma, meaning that you have an extra number of chromosomes in your myeloma cells. This is generally considered good. However, you do have a couple of intermediate / higher risk features on your cytogenetic testing, as well.
Specifically, you have a missing chromosome 13. This is not considered a risk factor when detected by FISH testing but is normal on conventional cytogenetic testing. In your case, it was picked up on conventional cytogenetic testing, so it would be considered an intermediate risk feature by Mayo Clinic criteria.
You also have an extra copy of chromosome 1. This is also considered a higher risk feature.
As far as what to do with this information, I would say that it will be important to consider the transplant option in first remission, as well as post-transplant consolidation and maintenance strategies, much in the same vein as mikeb on this posting.
On the positive side of things, it looks like you have had a very nice response to therapy based on blood and urine test results! As such, even if the marrow burden of plasma cells is higher than preferred, I think the transplant option should be on the table for discussion in light of your response to therapy (unless there are nuances in your case that cannot be gleaned from this posting). Upon recovery, the disease status could be re-evaluated and the pros / cons of post-transplant consolidation and/or maintenance therapy be discussed.
I hope this helps. Best wishes and take care!
Pete V.
-
Dr. Peter Voorhees - Name: Peter Voorhees, M.D.
Beacon Medical Advisor
Re: Help understanding cytogenics and karyotype
Dear all,
To clarify my previous post:
First, let me explain a bit about the difference between conventional cytogenetic and FISH testing for cytogenetic (chromosome) abnormalities.
Conventional cytogenetic testing requires that a myeloma cell be in the process of undergoing mitosis - in other words, actively in the process of dividing - in order to be analyzed. If the myeloma is a slow growing one, you might not catch any myeloma cells actively dividing. As such, the conventional cytogenetic testing can often be normal even when the FISH testing is abnormal. If the burden of myeloma cells in the sample is low, the cytogenetic testing is also often times normal (myeloma cells are typically not enriched prior to performing conventional cytogenetics).
The upside to conventional cytogenetic testing is that it allows the opportunity to look at all of the chromosomes in the myeloma cell. FISH will just pick up the abnormalities that the probes are designed to detect. FISH utilizes fluorescent probes that detect specific chromosome abnormalities.
The advantage to FISH is that the myeloma cell does not need to be actively dividing to look for the chromosome abnormality. Additionally, some chromosome changes (for example, the chromosome 4;14 translocation) are cryptic. In other words, they cannot be seen by conventional cytogenetic analysis. They are only easily detected by FISH testing. Lastly, a lab can purify the myeloma cells prior to performing FISH, which will increase the likelihood of finding a chromosome abnormality in the myeloma cells, even if the numbers of myeloma cells are relatively low.
Second, I mentioned that the chromosome 13 deletion in myeloma is only of significance if it is picked up on conventional cytogenetic testing. If it is picked up by FISH testing, but not on conventional cytogenetic testing, it is not considered significant. The thought is that, in the former case, the chromosome 13 deletion is being picked up in a more actively dividing myeloma. Hopefully this makes some sense.
Regardless, the chromosome 13 deletion picked up on conventional cytogenetic testing is considered an intermediate risk abnormality - not a high risk one.
I hope this helps clear things up.
Thanks!
Pete V.
To clarify my previous post:
First, let me explain a bit about the difference between conventional cytogenetic and FISH testing for cytogenetic (chromosome) abnormalities.
Conventional cytogenetic testing requires that a myeloma cell be in the process of undergoing mitosis - in other words, actively in the process of dividing - in order to be analyzed. If the myeloma is a slow growing one, you might not catch any myeloma cells actively dividing. As such, the conventional cytogenetic testing can often be normal even when the FISH testing is abnormal. If the burden of myeloma cells in the sample is low, the cytogenetic testing is also often times normal (myeloma cells are typically not enriched prior to performing conventional cytogenetics).
The upside to conventional cytogenetic testing is that it allows the opportunity to look at all of the chromosomes in the myeloma cell. FISH will just pick up the abnormalities that the probes are designed to detect. FISH utilizes fluorescent probes that detect specific chromosome abnormalities.
The advantage to FISH is that the myeloma cell does not need to be actively dividing to look for the chromosome abnormality. Additionally, some chromosome changes (for example, the chromosome 4;14 translocation) are cryptic. In other words, they cannot be seen by conventional cytogenetic analysis. They are only easily detected by FISH testing. Lastly, a lab can purify the myeloma cells prior to performing FISH, which will increase the likelihood of finding a chromosome abnormality in the myeloma cells, even if the numbers of myeloma cells are relatively low.
Second, I mentioned that the chromosome 13 deletion in myeloma is only of significance if it is picked up on conventional cytogenetic testing. If it is picked up by FISH testing, but not on conventional cytogenetic testing, it is not considered significant. The thought is that, in the former case, the chromosome 13 deletion is being picked up in a more actively dividing myeloma. Hopefully this makes some sense.
Regardless, the chromosome 13 deletion picked up on conventional cytogenetic testing is considered an intermediate risk abnormality - not a high risk one.
I hope this helps clear things up.
Thanks!
Pete V.
-
Dr. Peter Voorhees - Name: Peter Voorhees, M.D.
Beacon Medical Advisor
Re: Help understanding cytogenics and karyotype
Thank you Johanna, mikeb, and Dr. Peter Voorhees for your informative replies
Here is a bit of my history:
I suffered a spontaneous fracture of my distal femur on January 20, 2014 that was diagnosed as a large plasmacytoma. I underwent repair of the fracture at Beth Israel Deaconess Medical Center (BIDMC) in Boston and here I was diagnosed with multiple myeloma and also amyloidosis.
Bone marrow biopsy showed extensive involvement by plasma cell myeloma with 31% plasma cells on aspirate and more than 50% on the core. After fracture repair, I received radiation to the extensive tumor in my left femur and soon after an X-ray revealed another extensive tumor in my left tibia, so I received radiation to that.
In May, my oncologist at BIDMC encouraged me to go to the amyloidosis clinic at Boston Medical Center (BMC) for a complete 3-day workup and evaluation of the amyloidosis. A bone marrow biopsy there showed 50 to 70% plasma cells with kappa predominance. Amyloid organ involvement showed early heart and soft tissue involvement (carpal tunnel, etc) but preserved kidney function.
Going back to the subject of chromosome and cytogenic studies, I see that the report from BMC shows a FISH study was performed along with repeat of the karyotype.
As previously mentioned, the karyotype from February 2014 revealed:
55-60,X,-X,+1,add(1)(p12),t(1;5)(q32;q13),+2,+3,+4,+5,+6,+7,+9,
+11,+11,-13,+15,+15,-16,+17,+18,+19,add(20)(q11.2),+22[cp5]/
46,XX[16]
In May of 2014 the karotype showed:
55, X, -X, +1, add (1) (p12), t (1;5) (q32;q13), +3, +5, +6, +7, +11, +11, -13, +15, +15, -16, +18, +19, add (20) (q11.2), +22 [3] /46, XX [16]
The FISH results in May of 2014 showed:
My husband had a good question and wondered what the deletion of chromosome 16 means, if anything. After doing some research online, I read something about chromosome 16 having a tumor suppressor gene on it and I suppose if 16 is missing, that would not be a good thing. However, what I read may have nothing to do with myeloma and I may be way off-base. Any enlightenment on chromosome 16 would be appreciated.
As far as SCT goes, I should be getting there sooner rather than later. Because of the fractured femur and recovery thereof, the docs felt it better that I be walking (which I am now doing with a cane) and regain some physical strength and mobility before undergoing the SCT. My doc did say she would like to see the bone marrow biopsy come back at less than 20% before sending me to SCT (biopsy last month came back greater than 20%), so I have a ways to go yet. I do understand that the SCT seems to offer the best chance for a long-term remission and since I am a candidate, it is something I should pursue.
Again, thanks for reading and answering. I'm so grateful for this forum!
Here is a bit of my history:
I suffered a spontaneous fracture of my distal femur on January 20, 2014 that was diagnosed as a large plasmacytoma. I underwent repair of the fracture at Beth Israel Deaconess Medical Center (BIDMC) in Boston and here I was diagnosed with multiple myeloma and also amyloidosis.
Bone marrow biopsy showed extensive involvement by plasma cell myeloma with 31% plasma cells on aspirate and more than 50% on the core. After fracture repair, I received radiation to the extensive tumor in my left femur and soon after an X-ray revealed another extensive tumor in my left tibia, so I received radiation to that.
In May, my oncologist at BIDMC encouraged me to go to the amyloidosis clinic at Boston Medical Center (BMC) for a complete 3-day workup and evaluation of the amyloidosis. A bone marrow biopsy there showed 50 to 70% plasma cells with kappa predominance. Amyloid organ involvement showed early heart and soft tissue involvement (carpal tunnel, etc) but preserved kidney function.
Going back to the subject of chromosome and cytogenic studies, I see that the report from BMC shows a FISH study was performed along with repeat of the karyotype.
As previously mentioned, the karyotype from February 2014 revealed:
55-60,X,-X,+1,add(1)(p12),t(1;5)(q32;q13),+2,+3,+4,+5,+6,+7,+9,
+11,+11,-13,+15,+15,-16,+17,+18,+19,add(20)(q11.2),+22[cp5]/
46,XX[16]
In May of 2014 the karotype showed:
55, X, -X, +1, add (1) (p12), t (1;5) (q32;q13), +3, +5, +6, +7, +11, +11, -13, +15, +15, -16, +18, +19, add (20) (q11.2), +22 [3] /46, XX [16]
The FISH results in May of 2014 showed:
- Positive for gains of chromosome 5 and 15. Multiple hybridization signals for these chromosomes were observed in 76% of interphase cells examined.
- Positive for monosomy 13. Positive for deletion 13q14.3 and 13q34 in 82% of the interphase cells examined.
- There was no evidence of rearrangement or deletion of 14q32.3 or deletion of 17p13.1 and the centromeric region of chromosome 17.
- Interpretation and comments: Three cells had an ABNORMAL KAROTYPE similar to a prior study (2/3/2014) with gain of 1q, monosomy 13, and gains of odd numbered chromosomes, indicating persistence or recurrence of the patient’s known plasma cell disease. Concurrent FISH confirmed monosomy 13 and gains of chromosomes 5 and 15.
My husband had a good question and wondered what the deletion of chromosome 16 means, if anything. After doing some research online, I read something about chromosome 16 having a tumor suppressor gene on it and I suppose if 16 is missing, that would not be a good thing. However, what I read may have nothing to do with myeloma and I may be way off-base. Any enlightenment on chromosome 16 would be appreciated.
As far as SCT goes, I should be getting there sooner rather than later. Because of the fractured femur and recovery thereof, the docs felt it better that I be walking (which I am now doing with a cane) and regain some physical strength and mobility before undergoing the SCT. My doc did say she would like to see the bone marrow biopsy come back at less than 20% before sending me to SCT (biopsy last month came back greater than 20%), so I have a ways to go yet. I do understand that the SCT seems to offer the best chance for a long-term remission and since I am a candidate, it is something I should pursue.
Again, thanks for reading and answering. I'm so grateful for this forum!
-
Melpen - Name: Melissa
- Who do you know with myeloma?: myself
- When were you/they diagnosed?: Feb 5, 2014
- Age at diagnosis: 57
8 posts
• Page 1 of 1