Is there a correlation with percent of plasma cells in bone marrow aspirate and how quickly the disease progresses. If you have less than 20% bone marrow plasma cells abnormal does the disease progress slower than someone with 40% of abnormal plasma cells?
Is there a correlation with the percent of cells abnormal and cytogenetics with the chromosomal abnormalities? If less than 11% of cells on cytogenetics are expressing gains / deletions, does that impact progression ... or does simply having a negative progressive marker mean that the percent of cells with the deletions/gains does not matter. i.e. it either is there or isn't ... the percent is irrelevant.
If chromosomal abnormalities like gains 1q or deletion of 1p are indicative of advanced disease does that also correlate with a high number of abnormal plasma cells or is this not correlative?
Recognizing that surrogate markers are the primary measures in multiple myeloma is that why different markers are not correlated?
IOW's is it commonly seen that patients can have few plasma cells expressing abnormalities, with bone lucencies being the only end organ damage and yet still have advanced disease due to cytogenetics?
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Re: Plasma cell percentage & speed of progression
Dear Suzierose,
I am not sure how you are defining advanced disease -- disease associated with worse prognostic features or a high level of disease burden -- but I will try to answer your questions.
One of the reasons that we have moved from the Durie-Salmon staging system, which is an excellent barometer of disease burden (percent of abnormal plasma cells), to the International staging system for myeloma is that it is more predictive of outcome than the former. To my knowledge there is no correlation between the burden of abnormal plasma cells in the marrow and how quickly the disease progresses, at least in the case of symptomatic myeloma. Plus, there can be a great degree of variability in amount of disease burden from one sampled area to the next in a patient. We can go into the left side and find 20% involvement and then the right and see 80%.
The percentage of cells with cytogenetic abnormalities as a measure of prognosis has not been well studied. However, my guess is that the percentage of cells with high-risk cytogenetic features does not matter as much as the fact that the high risk cytogenetic lesion is present. The reason I say that is that the percentage of cytogenetically abnormal cells (by conventional cytogenetics or FISH) is subject to technical limitations. For example, if the bone marrow aspirate is diluted with peripheral blood, the number of abnormal cells by FISH will drop. On the other hand, if the laboratory purifies the plasma cells from all of the other cells in the bone marrow aspirate first and then does the cytogenetic testing, there may be some prognostic significance. The IFM group has looked at the percentage of purified plasma cells with the 17p deletion and found that patients with a higher proportion of plasma cells with the 17p deletion (not the total marrow population of cells) do not do as well. In their hands, having >60% of the plasma cells affected by the 17p deletion was worse than those who had less.
At the end of the day, international stage, high risk cytogenetic abnormalities, high risk gene expression profile, kidney failure, high LDH, etc are the most important measures of long term outcome and trump measures of high disease burden (e.g Durie-Salmon staging).
I hope I answered your questions . Good luck and hang in there!
Pete V.
I am not sure how you are defining advanced disease -- disease associated with worse prognostic features or a high level of disease burden -- but I will try to answer your questions.
One of the reasons that we have moved from the Durie-Salmon staging system, which is an excellent barometer of disease burden (percent of abnormal plasma cells), to the International staging system for myeloma is that it is more predictive of outcome than the former. To my knowledge there is no correlation between the burden of abnormal plasma cells in the marrow and how quickly the disease progresses, at least in the case of symptomatic myeloma. Plus, there can be a great degree of variability in amount of disease burden from one sampled area to the next in a patient. We can go into the left side and find 20% involvement and then the right and see 80%.
The percentage of cells with cytogenetic abnormalities as a measure of prognosis has not been well studied. However, my guess is that the percentage of cells with high-risk cytogenetic features does not matter as much as the fact that the high risk cytogenetic lesion is present. The reason I say that is that the percentage of cytogenetically abnormal cells (by conventional cytogenetics or FISH) is subject to technical limitations. For example, if the bone marrow aspirate is diluted with peripheral blood, the number of abnormal cells by FISH will drop. On the other hand, if the laboratory purifies the plasma cells from all of the other cells in the bone marrow aspirate first and then does the cytogenetic testing, there may be some prognostic significance. The IFM group has looked at the percentage of purified plasma cells with the 17p deletion and found that patients with a higher proportion of plasma cells with the 17p deletion (not the total marrow population of cells) do not do as well. In their hands, having >60% of the plasma cells affected by the 17p deletion was worse than those who had less.
At the end of the day, international stage, high risk cytogenetic abnormalities, high risk gene expression profile, kidney failure, high LDH, etc are the most important measures of long term outcome and trump measures of high disease burden (e.g Durie-Salmon staging).
I hope I answered your questions . Good luck and hang in there!
Pete V.
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Dr. Peter Voorhees - Name: Peter Voorhees, M.D.
Beacon Medical Advisor
Re: Plasma cell percentage & speed of progression
Dr Voorhees,
You sorted out what I was trying to ask. I was unable to determine how advanced was defined.
Your answer helped in that it is not just the % of abnormal plasma cell burden. Which was
part of my consternation. And made me uncertain about what parameter should be being used to assess complete response as well as progression of disease. I am a patient that only has the B in CRAB, and a low plasma cell burden but a poor cytogentic profile. That 17p
Very interesting to learn that right or left BM can have tremendous variation. I also wonder why that is. Has anyone figured that out?
That purification technique is very helpful to know as well, since without it the % within the total population of cells can be misleadingly low. And that was what was confounding me too. Just couldn't put those pieces together. However, I did understand when you said having it present is the issue not the percent within total population of cells
Can patients request that their plasma cells be purfied first prior to the cytogentic testing? Seems that technique, if not routine, would be a significant factor if cytogentics are being used for risk stratification. I could not figure out why they were calling it advanced disease even though the plasma cell burden was low. Particularly, as journal articles said that the 17p is indicative of 'advanced' multiple myeloma, as those chromosomal changes tend to show up in the late disease stage. I was unable to put those 2 variables together; low abnormal plasma cells along with it being late stage, chromosomally.
Thanks for sorting that out.
Your response was very helpful.
Made a lot more sense, of what is being seen on labs.
And I believe I can now formulate a better question, too, when it comes to having 'advanced' multiple myeloma.
Thanks again.
suzie
You sorted out what I was trying to ask. I was unable to determine how advanced was defined.
Your answer helped in that it is not just the % of abnormal plasma cell burden. Which was
part of my consternation. And made me uncertain about what parameter should be being used to assess complete response as well as progression of disease. I am a patient that only has the B in CRAB, and a low plasma cell burden but a poor cytogentic profile. That 17p
Very interesting to learn that right or left BM can have tremendous variation. I also wonder why that is. Has anyone figured that out?
That purification technique is very helpful to know as well, since without it the % within the total population of cells can be misleadingly low. And that was what was confounding me too. Just couldn't put those pieces together. However, I did understand when you said having it present is the issue not the percent within total population of cells
Can patients request that their plasma cells be purfied first prior to the cytogentic testing? Seems that technique, if not routine, would be a significant factor if cytogentics are being used for risk stratification. I could not figure out why they were calling it advanced disease even though the plasma cell burden was low. Particularly, as journal articles said that the 17p is indicative of 'advanced' multiple myeloma, as those chromosomal changes tend to show up in the late disease stage. I was unable to put those 2 variables together; low abnormal plasma cells along with it being late stage, chromosomally.
Thanks for sorting that out.
Your response was very helpful.
Made a lot more sense, of what is being seen on labs.
And I believe I can now formulate a better question, too, when it comes to having 'advanced' multiple myeloma.
Thanks again.
suzie
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suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: Plasma cell percentage & speed of progression
I believe what he meant on the left vs right variation is just that it's random if the needle happened to go into an area of marrow that happened to have a "hot spot" of myeloma cells or not.
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rumnting - Who do you know with myeloma?: husband
- When were you/they diagnosed?: 4/9/11
- Age at diagnosis: 54
Re: Plasma cell percentage & speed of progression
I have been following this site since diagnosed & this post encouraged me to jump in. After years of being followed for progressively high sed rate with diagnosis of undetermined autoimmune disease, in May/June of this year I was referred & diagnosed with IgA lambda monoclonal gammopathy. Extensive testing was done , I have no CRAB symptoms (last month borderline hemoglobin-11.8) but the bone marrow biopsy showed 70% plasma cells (FISH done no chromosome abnormalities).
This was followed by a second opinion in July. Based on testing, they said I presented atypically but appeared to be smoldering or stage 1. Because of the BMB , they said I should probably start treatment. After more research and not wanting to negatively affect treatment but also not wanting to start treatment before needed , in August I had a discussion with the oncologist re the only reason I would start treatment was the BMB (and it seems that can vary)--so did it make sense to wait and just follow the labs monthly. She agreed and we have followed in aug/sep with no change and will be going back this week for october labs.
I would like opinion on this. Also, I seem to have constant drainage/congestion which they said could be associated with IgA type. Outside of treatment, is there anything to help with that.
Thanks!
This was followed by a second opinion in July. Based on testing, they said I presented atypically but appeared to be smoldering or stage 1. Because of the BMB , they said I should probably start treatment. After more research and not wanting to negatively affect treatment but also not wanting to start treatment before needed , in August I had a discussion with the oncologist re the only reason I would start treatment was the BMB (and it seems that can vary)--so did it make sense to wait and just follow the labs monthly. She agreed and we have followed in aug/sep with no change and will be going back this week for october labs.
I would like opinion on this. Also, I seem to have constant drainage/congestion which they said could be associated with IgA type. Outside of treatment, is there anything to help with that.
Thanks!
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carolc - Name: carol
- Who do you know with myeloma?: myself
- When were you/they diagnosed?: 6/11
- Age at diagnosis: 54
Re: Plasma cell percentage & speed of progression
In your case and cases like it, it is often difficult to decide "the right course of action." As you stated, treatment in myeloma is primarily based on the presence of end organ damage or the CRAB"I" criteria. In your case, although you have a significant disease burden, with 70% plasma cells noted on the bone marrow biopsy, it is not causing measurable end organ damage. Hence, your diagnosis of smoldering multiple myeloma and an option to undergo active surveillance without therapy.
Within this category of disease, research has suggested that risk of progression can be estimated based on the percent plasma cells (>10%), M-spike (>3gm/dL), and an abmormal serum free light chain ratio (>8 or <0.125). This work was published in 2008 (Dispenzieri et al Blood). Analysis of these populations of smoldering myeloma patients demonstrated that individuals with 1 risk factor had a median time to progression of 10 years; 2 risk factors TTP was 5.1 years; and 3 risk factors TTP was 1.9 months. An important question is, when do we decide to treat? Although you do not have measurable end organ damage, our job is to start treatment at a point prior to you having significant issues (increases in M-spike, a negative trend in your hemaglobin etc).
Addressing your case specifically, what do we do with people who have a large bone marrow burden of tumor cells, but no CRAB symptoms? A recent publication out of Mayo Clinic in Rochester, MN suggests an answer to this question (Rajkumar et al NEJM 2011). The authors retrospectively examined 655 patients with smoldering myeloma between 1996 and 2010. Of those patients, only 21 had equal to or greater than 60% plasma cells in the marrow at diagnosis (3.2%). This data revealed that the median time to progression for patients with SMM and >60% plasma cells in their marrow was only 7 months. Further, 95% of patients progressed to active disease with 2 years. These data suggest that individuals with equal to or greater than 60% plasma cells identified on biopsy have a different biology than those with less than 60% and are going to progress at a more rapid rate. These data were in concordance with a prior publication be the authors looking at smaller numbers of patients(Kyle NEJM 2007).
Does this change your management? Not necessarily, it comes down to your comfort with monthly labs and with the knowledge that you may progress to active disease soon. I cannot argue that no drugs are better than therapy in terms of quality of life. For the patients that I see in a situation like yours, I tend to recommend initiation of therapy. The available data suggests that your disease will progress soon. But as I said there is no absolute and I cannot tell you that it will change the outcome of therapy (survival).
Symptom control is best for the your potentially related symptoms. And keep an eye out for fevers or progression of the sinus issues to infections. I do not know your Ig levels, but with myeloma you are at a increase for infections.
I hope that this helps.
Within this category of disease, research has suggested that risk of progression can be estimated based on the percent plasma cells (>10%), M-spike (>3gm/dL), and an abmormal serum free light chain ratio (>8 or <0.125). This work was published in 2008 (Dispenzieri et al Blood). Analysis of these populations of smoldering myeloma patients demonstrated that individuals with 1 risk factor had a median time to progression of 10 years; 2 risk factors TTP was 5.1 years; and 3 risk factors TTP was 1.9 months. An important question is, when do we decide to treat? Although you do not have measurable end organ damage, our job is to start treatment at a point prior to you having significant issues (increases in M-spike, a negative trend in your hemaglobin etc).
Addressing your case specifically, what do we do with people who have a large bone marrow burden of tumor cells, but no CRAB symptoms? A recent publication out of Mayo Clinic in Rochester, MN suggests an answer to this question (Rajkumar et al NEJM 2011). The authors retrospectively examined 655 patients with smoldering myeloma between 1996 and 2010. Of those patients, only 21 had equal to or greater than 60% plasma cells in the marrow at diagnosis (3.2%). This data revealed that the median time to progression for patients with SMM and >60% plasma cells in their marrow was only 7 months. Further, 95% of patients progressed to active disease with 2 years. These data suggest that individuals with equal to or greater than 60% plasma cells identified on biopsy have a different biology than those with less than 60% and are going to progress at a more rapid rate. These data were in concordance with a prior publication be the authors looking at smaller numbers of patients(Kyle NEJM 2007).
Does this change your management? Not necessarily, it comes down to your comfort with monthly labs and with the knowledge that you may progress to active disease soon. I cannot argue that no drugs are better than therapy in terms of quality of life. For the patients that I see in a situation like yours, I tend to recommend initiation of therapy. The available data suggests that your disease will progress soon. But as I said there is no absolute and I cannot tell you that it will change the outcome of therapy (survival).
Symptom control is best for the your potentially related symptoms. And keep an eye out for fevers or progression of the sinus issues to infections. I do not know your Ig levels, but with myeloma you are at a increase for infections.
I hope that this helps.
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Dr. Ken Shain - Name: Ken Shain, M.D., Ph.D.
Beacon Medical Advisor
Re: Plasma cell percentage & speed of progression
Dr. Shain,
Thanks for your response. Wondering if it's possible, as stated above, where the percent of plasma cell could differ greatly from one side or area to the other ? In that case, I assume my labs are still the best indication. My IG levels from September are: IGG-205, IGA-927, IGM-21 and free lights chains from October are: kappa-0.01 & lambda-42.00 and serum protein was 7.3
thanks!.
Thanks for your response. Wondering if it's possible, as stated above, where the percent of plasma cell could differ greatly from one side or area to the other ? In that case, I assume my labs are still the best indication. My IG levels from September are: IGG-205, IGA-927, IGM-21 and free lights chains from October are: kappa-0.01 & lambda-42.00 and serum protein was 7.3
thanks!.
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carolc - Name: carol
- Who do you know with myeloma?: myself
- When were you/they diagnosed?: 6/11
- Age at diagnosis: 54
Re: Plasma cell percentage & speed of progression
Dear Carol,
I agree with Dr. Shain completely. In smoldering myeloma, the burden of disease does matter. Perhaps my example of variability of disease burden from one spot to the next was overstated. Yes, I have seen this degree of variability but that is a somewhat unusual circumstance. In the study that Dr. Shain quoted, they did not do multiple biopsies in the same patient to see if there was variability from one spot to the next. If someone had smoldering myeloma with >60% plasma cells on a single biopsy specimen, they had a high rate of conversion to symptomatic disease and quite quickly. Your hemoglobin is on the low-ish side, suggesting that your marrow is beginning to struggle a bit with this disease burden. Treatment now is a very reasonable course of action under the circumstances. If observation is pursued, make sure it is close observation.
Good luck!
Pete V.
I agree with Dr. Shain completely. In smoldering myeloma, the burden of disease does matter. Perhaps my example of variability of disease burden from one spot to the next was overstated. Yes, I have seen this degree of variability but that is a somewhat unusual circumstance. In the study that Dr. Shain quoted, they did not do multiple biopsies in the same patient to see if there was variability from one spot to the next. If someone had smoldering myeloma with >60% plasma cells on a single biopsy specimen, they had a high rate of conversion to symptomatic disease and quite quickly. Your hemoglobin is on the low-ish side, suggesting that your marrow is beginning to struggle a bit with this disease burden. Treatment now is a very reasonable course of action under the circumstances. If observation is pursued, make sure it is close observation.
Good luck!
Pete V.
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Dr. Peter Voorhees - Name: Peter Voorhees, M.D.
Beacon Medical Advisor
Re: Plasma cell percentage & speed of progression
Dr. Voorhees,
Thank you so much for your response.
Thank you so much for your response.
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carolc - Name: carol
- Who do you know with myeloma?: myself
- When were you/they diagnosed?: 6/11
- Age at diagnosis: 54
Re: Plasma cell percentage & speed of progression
What test do I request to determine if >60% of the plasma cells have del 17p?
I have had FISH test but I do not believe it is providing the level of specificity you indicate in terms of purifying the plasma cells from all the other cells in the aspirate prior to FISH.
Perhaps, I need to request that the purification is done prior to doing the FISH?
Or is that something the physician has to specify to the lab?
Also does the lab report out the technique they utilized on the cytogentic results?
If so, what would it say that would indicate that it was purified plasma cells from aspirate vs. all cells from bone marrow aspirate?
Thank you kindly.
SuzieRose
I have had FISH test but I do not believe it is providing the level of specificity you indicate in terms of purifying the plasma cells from all the other cells in the aspirate prior to FISH.
Perhaps, I need to request that the purification is done prior to doing the FISH?
Or is that something the physician has to specify to the lab?
Also does the lab report out the technique they utilized on the cytogentic results?
If so, what would it say that would indicate that it was purified plasma cells from aspirate vs. all cells from bone marrow aspirate?
Thank you kindly.
SuzieRose
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suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
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