I received a copy of my bone marrow biopsy report and feel quite relieved that the results were below 10% and consistent with MGUS. Since my IgA M-spike is only 0.6 g/dL, which I see as more of a blip than a spike, I am feeling much relief in being "statistically safe".
The question I have is regarding how the results were expressed. The report states "clonal plasma cells, approximately 5-8% of marrow elements". When I saw this, I thought that there is a rather large spread between 5 and 8. It simply does not look very specific, more like an estimate than an actual count.
Is the bone marrow plasma cell percentage commonly expressed as an approximation? Are IgA proteins difficult to measure accurately in bone marrow like they are in some of the blood tests?
I would appreciate any insight that might be offered. A little knowledge leads one to a lot of questions. Thanks!
Take good care.
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kap12 - Name: Kristine
- Who do you know with myeloma?: Myself (IgA MGUS)
- When were you/they diagnosed?: September 2016
Re: Accuracy of bone marrow plasma cell percentage?
The paper below discusses the various methods of estimating the percentage (though it might be somewhat out of date) as well as their prognostic significance:
No method is perfectly accurate (two of them involve manual counting and one is a visual estimate) but < 10% is obviously reassuring.
Rajkumar, SV, et al, "Methods for estimation of bone marrow plasma cell involvement in myeloma: Predictive value for response and survival in patients undergoing autologous stem cell transplantation," American Journal of Hematology, Dec 2001 (abstract, full-text PDF)
Abstract:
In myeloma, the bone marrow plasma cell percentage (BMPC%) is usually estimated independently on the aspirate, core biopsy, and plasma cell labeling index (PCLI) samples. This study was done to determine which of the 3 individual estimates correlates best with complete response (CR) and survival. Seventy-five consecutive patients who underwent SCT for relapsed myeloma were studied. The median BMPC% on the marrow aspirate, core biopsy, and PCLI studies were 20, 25, and 20, respectively. There was a significant correlation between the three methods, ρ > 0.65, P < 0.001. However, in 8% of patients the BMPC% was different by an absolute value of 50% between methods. No individual method was predictive for CR. However, the highest estimate of the BMPC% among the three methods was a significant predictor of CR (P = 0.02). Survival following SCT was longer among patients with a low BMPC% (≤60) by the PCLI method compared to those with higher values, median survival 23 versus 7 months, respectively, P = 0.02. PFS was also different, with survival times of 11 and 5 months, respectively, P = 0.003. Similar results were obtained when the highest estimate of the BMPC% was used in survival analysis (P = 0.02 and 0.004, respectively). Statistical significance was lower when the BMPC% on the aspirate or biopsy used in survival analysis. Compared to any individual method of estimating BMPC%, the highest estimate of the BMPC% is the best predictor of CR in myeloma. It is also prognostic for poor survival and PFS following SCT for myeloma. We recommend that all three methods of estimating BMPC% be routinely performed and that the highest value be used for prognostic purposes.
No method is perfectly accurate (two of them involve manual counting and one is a visual estimate) but < 10% is obviously reassuring.
Rajkumar, SV, et al, "Methods for estimation of bone marrow plasma cell involvement in myeloma: Predictive value for response and survival in patients undergoing autologous stem cell transplantation," American Journal of Hematology, Dec 2001 (abstract, full-text PDF)
Abstract:
In myeloma, the bone marrow plasma cell percentage (BMPC%) is usually estimated independently on the aspirate, core biopsy, and plasma cell labeling index (PCLI) samples. This study was done to determine which of the 3 individual estimates correlates best with complete response (CR) and survival. Seventy-five consecutive patients who underwent SCT for relapsed myeloma were studied. The median BMPC% on the marrow aspirate, core biopsy, and PCLI studies were 20, 25, and 20, respectively. There was a significant correlation between the three methods, ρ > 0.65, P < 0.001. However, in 8% of patients the BMPC% was different by an absolute value of 50% between methods. No individual method was predictive for CR. However, the highest estimate of the BMPC% among the three methods was a significant predictor of CR (P = 0.02). Survival following SCT was longer among patients with a low BMPC% (≤60) by the PCLI method compared to those with higher values, median survival 23 versus 7 months, respectively, P = 0.02. PFS was also different, with survival times of 11 and 5 months, respectively, P = 0.003. Similar results were obtained when the highest estimate of the BMPC% was used in survival analysis (P = 0.02 and 0.004, respectively). Statistical significance was lower when the BMPC% on the aspirate or biopsy used in survival analysis. Compared to any individual method of estimating BMPC%, the highest estimate of the BMPC% is the best predictor of CR in myeloma. It is also prognostic for poor survival and PFS following SCT for myeloma. We recommend that all three methods of estimating BMPC% be routinely performed and that the highest value be used for prognostic purposes.
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Davidg - Name: David
- When were you/they diagnosed?: Feb 2015 - AL Amyloidosis
- Age at diagnosis: 53
Re: Accuracy of bone marrow plasma cell percentage?
Hello Kristine:
This part of the test, I believe, is strictly a technician looking at plasma cells under a microscope, and so its usually quoted within five percent or ten percent intervals. Even though its not overly precise, it is useful.
A healthy person's plasma cell percentage is usually in the range of 2 to 4 percent. So if the percentage is anything above 5%, there is excess plasma cells, presumed to be related to the MGUS (in your case). Having a level below 10%, and having no symptoms, is consistent with the MGUS, which could potentially remain relatively dormant for many many years.
There is a more sensitive test with more fine results based on precision optical equipment, and staining of the sample. The flow cytometry analysis can detect the number of cells down to one in a hundred thousand, or better. I am not sure that is needed in your case, but you can ask your doctor if it was done. That typically takes a little longer to do.
Good luck.
This part of the test, I believe, is strictly a technician looking at plasma cells under a microscope, and so its usually quoted within five percent or ten percent intervals. Even though its not overly precise, it is useful.
A healthy person's plasma cell percentage is usually in the range of 2 to 4 percent. So if the percentage is anything above 5%, there is excess plasma cells, presumed to be related to the MGUS (in your case). Having a level below 10%, and having no symptoms, is consistent with the MGUS, which could potentially remain relatively dormant for many many years.
There is a more sensitive test with more fine results based on precision optical equipment, and staining of the sample. The flow cytometry analysis can detect the number of cells down to one in a hundred thousand, or better. I am not sure that is needed in your case, but you can ask your doctor if it was done. That typically takes a little longer to do.
Good luck.
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JPC - Name: JPC
Re: Accuracy of bone marrow plasma cell percentage?
Thanks, JPC. I was definitely doing the happy dance over the bone marrow biopsy results! It just seems odd to see that sort of reporting in a world of overwhelming numerical minutiae.
I checked my report and it says that flow cytometry was not performed. Cytogenetics are pending.
Although all of my numbers are looking very good, the hematologist discussed my case with her colleagues and has now requested that I have CT scans. Odd, but it isn't like having to lie down to give bone marrow for an estimate!
Take good care.
Kristine
I checked my report and it says that flow cytometry was not performed. Cytogenetics are pending.
Although all of my numbers are looking very good, the hematologist discussed my case with her colleagues and has now requested that I have CT scans. Odd, but it isn't like having to lie down to give bone marrow for an estimate!
Take good care.
Kristine
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kap12 - Name: Kristine
- Who do you know with myeloma?: Myself (IgA MGUS)
- When were you/they diagnosed?: September 2016
Re: Accuracy of bone marrow plasma cell percentage?
Davidg,
Thanks so much for the reference article and excerpt. Being very new at this, it takes me quite a while to comprehend what articles such as this are actually saying. I'll continue to work at it, nonetheless. If only there were subtitles!
My hematologist was the luck of the draw through a referral, very new, and not particularly forthcoming with information. I think my lack of confidence has led me into over-analyzing every result from every test. Since the bone marrow biopsy was the most invasive test I thought it would be the most refined. I am beginning to see the reason there are so many different tests involved in reaching a diagnosis.
Take good care.
Kristine
Thanks so much for the reference article and excerpt. Being very new at this, it takes me quite a while to comprehend what articles such as this are actually saying. I'll continue to work at it, nonetheless. If only there were subtitles!
My hematologist was the luck of the draw through a referral, very new, and not particularly forthcoming with information. I think my lack of confidence has led me into over-analyzing every result from every test. Since the bone marrow biopsy was the most invasive test I thought it would be the most refined. I am beginning to see the reason there are so many different tests involved in reaching a diagnosis.
Take good care.
Kristine
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kap12 - Name: Kristine
- Who do you know with myeloma?: Myself (IgA MGUS)
- When were you/they diagnosed?: September 2016
Re: Accuracy of bone marrow plasma cell percentage?
Hi Kristine,
You've gotten some helpful feedback already. I just wanted to mention one or two additional things that might round out the discussion a bit.
First, because the plasma cell percentage is based on a sample of bone marrow cells, there is automatically a "confidence interval" around the percentage estimate. Basic statistics requires it. You are the percentage based on a sample, rather than every single marrow cells.
So, just as an example, if a plasma cell percentage estimate is 7%, and it is based on a sample of 300 bone marrow cells, then the 95% confidence interval ranges from 4.11% to 9.89%. In other words, there is a 95% probability that the true plasma cell percentage for that area of the bone marrow is somewhere between 4.11% and 9.89%.
I think this purely statistical uncertainty is one of the main reasons for the range quoted in your report.
The other thing to keep in mind is that myeloma is often a "patchy" disease. There will be areas of the bone marrow where the disease is more present, and areas where it is less present. So the estimate you got may be higher or lower than the actual plasma cell percentage in other parts of your body.
Finally, if you really want to get technical. there is also the issue of whether the plasma cell percentages is based on the aspirate sample or the core sample. Here are two forum threads that discuss that issue (but remember: this is really a technical issue):
"Why difference in BMB aspirate vs. core biopsy results?" (Feb 25, 2013)
"What is the correct plasma cell percentage to use?" (Aug 19, 2015)
Good luck!
You've gotten some helpful feedback already. I just wanted to mention one or two additional things that might round out the discussion a bit.
First, because the plasma cell percentage is based on a sample of bone marrow cells, there is automatically a "confidence interval" around the percentage estimate. Basic statistics requires it. You are the percentage based on a sample, rather than every single marrow cells.
So, just as an example, if a plasma cell percentage estimate is 7%, and it is based on a sample of 300 bone marrow cells, then the 95% confidence interval ranges from 4.11% to 9.89%. In other words, there is a 95% probability that the true plasma cell percentage for that area of the bone marrow is somewhere between 4.11% and 9.89%.
I think this purely statistical uncertainty is one of the main reasons for the range quoted in your report.
The other thing to keep in mind is that myeloma is often a "patchy" disease. There will be areas of the bone marrow where the disease is more present, and areas where it is less present. So the estimate you got may be higher or lower than the actual plasma cell percentage in other parts of your body.
Finally, if you really want to get technical. there is also the issue of whether the plasma cell percentages is based on the aspirate sample or the core sample. Here are two forum threads that discuss that issue (but remember: this is really a technical issue):
"Why difference in BMB aspirate vs. core biopsy results?" (Feb 25, 2013)
"What is the correct plasma cell percentage to use?" (Aug 19, 2015)
Good luck!
Re: Accuracy of bone marrow plasma cell percentage?
Thank you, TerryH, for expanding on the feedback. Your comments and reading more information has helped me get a clearer picture of how bone marrow percentages are calculated. It appears that my percentage (5-8%) was drawn from CD138 staining. This leads to more questions, of course.
If the percentage represents the total plasma cell count, including both normal and monoclonal plasma cells, would suppression of uninvolved cells mean that monoclonal cells actually make up a greater part of that percentage? (In an earlier post, Multibilly pointed out that my uninvolved isotypes were somewhat low.)
Also, is focal clustering anything significant? The remarks on my results say "Most plasma cells are present singly; however focally the plasma cells are clustered". After describing lab test procedures, the report goes on to say "the majority of the plasma cells express kappa light chain." Is that just restating what was already known from the blood test, that I have IgA kappa MGUS?
I am really just trying to understand the concepts, not trying to read more into this than what is there. At this juncture, my biggest concern is understanding what is important to keep track of over time. Thanks for your help!
Take good care.
If the percentage represents the total plasma cell count, including both normal and monoclonal plasma cells, would suppression of uninvolved cells mean that monoclonal cells actually make up a greater part of that percentage? (In an earlier post, Multibilly pointed out that my uninvolved isotypes were somewhat low.)
Also, is focal clustering anything significant? The remarks on my results say "Most plasma cells are present singly; however focally the plasma cells are clustered". After describing lab test procedures, the report goes on to say "the majority of the plasma cells express kappa light chain." Is that just restating what was already known from the blood test, that I have IgA kappa MGUS?
I am really just trying to understand the concepts, not trying to read more into this than what is there. At this juncture, my biggest concern is understanding what is important to keep track of over time. Thanks for your help!
Take good care.
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kap12 - Name: Kristine
- Who do you know with myeloma?: Myself (IgA MGUS)
- When were you/they diagnosed?: September 2016
7 posts
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