My wife had an allogeneic stem cell transplant last December. Recently (July), the lab and bone marrow biopsy result indicated a 0.5 paraprotein (spike, probably monoclonal gamma region) and the bone marrow biopsy result indicated 2% P (for polyclonal plasma cells) instead of monoclonal plasma cells (like the results prior to the stem cell transplant).
How can the plasma cells in the bone marrow be polyclonal, yet the serum paraprotein is 0.5 probably monoclonal in the gamma region? Also, why does this particular test only indicate "probably"?
The doctor seems to believe the P is good and her cells are 100% donor. Her kappa-lambda ratio has normalized at 1.49. But we are concerned about the remaining paraprotein level.
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Re: Possible conflict between SPEP & bone marrow results?
Hi Falcon,
Glad to see that the allo is working out so well!
First off, what did the serum immunofixation test state? That is the test you should rely on to see if any monoclonal protein is present in the serum or not. It's much more accurate than an SPEP in telling you if any monoclonal protein is present.
Also, SPEP measurements are not exactly precise because other proteins occupy the same area of the SPEP graph that an M-spike will occupy, and the test can't exactly differentiate between what part of the overall spike is polyclonal (normal) and what part is monoclonal. Because of this, there are practical limits to how accurate an M-spike reading is, especially at low m-spike levels like 0.5 g/dL. The practical limit of the SPEP fairly accurately measuring an m-spike in the gamma region is 0.3 - 0.5 g/dL (the limit is 0.7 g/dL in the alpha or beta regions). So, in your case, you are hitting the practical limit of the SPEP test, which then calls into question the accuracy of the reading and whether the small spike they are seeing in the gamma region is polyclonal or monoclonal.
If you want to get into the nits of this topic, see this article:
Leung, Nelson, "Clinical Tests for Monoclonal Proteins," Chapter 8 of American Society of Nephrology Onco-Nephrology Curriculum, 2016 (full text of chapter [PDF])
The other thing to consider is that bone marrow biopsy tests are a bit "hit and miss" when it comes to measuring bone marrow plasma cell percentages and catching a representative mix of plasma cells. That's because myeloma is not spread uniformly throughout one's bone marrow. So, even with some disease present in the bone marrow, the test can potentially hit a pocket of completely normal cells or a pocket with a mixture of normal and abnormal cells.
Now, having said all this, I would take the results of 2% normal bone marrow plasma cells + normal FLC values + a questionable M-spike as being extremely good news. But if you want to chase this down further, you could also request a 24-hour UPEP and, as mentioned before, go back and look at the serum immunofixation results.
Again, congrats on the great response!
Glad to see that the allo is working out so well!
First off, what did the serum immunofixation test state? That is the test you should rely on to see if any monoclonal protein is present in the serum or not. It's much more accurate than an SPEP in telling you if any monoclonal protein is present.
Also, SPEP measurements are not exactly precise because other proteins occupy the same area of the SPEP graph that an M-spike will occupy, and the test can't exactly differentiate between what part of the overall spike is polyclonal (normal) and what part is monoclonal. Because of this, there are practical limits to how accurate an M-spike reading is, especially at low m-spike levels like 0.5 g/dL. The practical limit of the SPEP fairly accurately measuring an m-spike in the gamma region is 0.3 - 0.5 g/dL (the limit is 0.7 g/dL in the alpha or beta regions). So, in your case, you are hitting the practical limit of the SPEP test, which then calls into question the accuracy of the reading and whether the small spike they are seeing in the gamma region is polyclonal or monoclonal.
If you want to get into the nits of this topic, see this article:
Leung, Nelson, "Clinical Tests for Monoclonal Proteins," Chapter 8 of American Society of Nephrology Onco-Nephrology Curriculum, 2016 (full text of chapter [PDF])
The other thing to consider is that bone marrow biopsy tests are a bit "hit and miss" when it comes to measuring bone marrow plasma cell percentages and catching a representative mix of plasma cells. That's because myeloma is not spread uniformly throughout one's bone marrow. So, even with some disease present in the bone marrow, the test can potentially hit a pocket of completely normal cells or a pocket with a mixture of normal and abnormal cells.
Now, having said all this, I would take the results of 2% normal bone marrow plasma cells + normal FLC values + a questionable M-spike as being extremely good news. But if you want to chase this down further, you could also request a 24-hour UPEP and, as mentioned before, go back and look at the serum immunofixation results.
Again, congrats on the great response!
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Possible conflict between SPEP & bone marrow results?
Thank you Multibilly for the great explanation.
We now have new test results that were added yesterday, and the paraprotein appears to have crept up slightly to 0.71. Possibly, this value is a mix of polyclonal and monoclonal?
The kappa and lambda had both been in the normal range until this past week, but now, both values are increasing and are high, slightly out of range. The ratio is also slightly elevated at about 2.0. Not sure why the lambda is increasing. In the past, during a relapse, the kappa would go higher and the lambda would go very low. Possibly, this has something to do with the polyclonal result in the bone marrow? Maybe it could be an inflammatory response causing the lambda to climb. She has had some graft-versus-host disease (GVHD).
I checked the listing of lab results and it does not appear that a serum immunofixation test has been performed.
We now have new test results that were added yesterday, and the paraprotein appears to have crept up slightly to 0.71. Possibly, this value is a mix of polyclonal and monoclonal?
The kappa and lambda had both been in the normal range until this past week, but now, both values are increasing and are high, slightly out of range. The ratio is also slightly elevated at about 2.0. Not sure why the lambda is increasing. In the past, during a relapse, the kappa would go higher and the lambda would go very low. Possibly, this has something to do with the polyclonal result in the bone marrow? Maybe it could be an inflammatory response causing the lambda to climb. She has had some graft-versus-host disease (GVHD).
I checked the listing of lab results and it does not appear that a serum immunofixation test has been performed.
Re: Possible conflict between SPEP & bone marrow results?
Hi Falcon,
First off, an M-spike of 0.71 g/dL in the gamma zone likely does mean its monoclonal. There's always bit of inaccuracy with SPEP test results, but given the new magnitude of her M-spike, it seems pretty clear that your wife does have a monoclonal m-spike in the ballpark of 0.7 g/dL. Does the most recent SPEP lab report indicate any uncertainty in this latest figure like the previous report did?
Secondly, are you saying that both the lambda and kappa free light chain values are high and out of range, along with the FLC ratio? What exactly are all those FLC values? If all three values are high, that "may" suggest renal impairment. See this table posted by Ron Harvot to understand what various combinations of FLC values mean:
https://myelomabeacon.org/forum/increase-in-free-light-chains-t5384.html#p31517
(Table also available here.)
A quick way to help verify if your wife's renal function is normal is to look see if her creatinine and eGFR values on the comprehensive metabolic panel are both in the normal range.
Lastly, it might be a good idea to get a new serum immunofixation test to verify her current isotype (e.g. IgG kappa, etc). Transplants can sometimes cause isotype switches, where the disease might switch from being something like IgG kappa to another combination such as IgG lambda. This is especially true in allo transplants. Transplants can also produce multiple M-spikes with different isotypes (e.g. you can have both IgG-kappa and IgG-lambda monoclonal protein where there was only type present before the transplant). Either of these things can change how your free light chain numbers behave. But you need a serum immunofixation test to tell you if these things may be occurring. Note that none of these phenomena are considered to be bad things.
Having said all this, it's important to remember that lots of things can come and go in the first few months post-transplant and various lab figures can appear a bit "whacky" as your wife's immune system is reconstituted and the donor's immune system is engrafted, all while dealing with GVHD. Her oncologist is best suited to comment on all these latest numbers, especially given that her body is still undergoing changes from the recent transplant.
First off, an M-spike of 0.71 g/dL in the gamma zone likely does mean its monoclonal. There's always bit of inaccuracy with SPEP test results, but given the new magnitude of her M-spike, it seems pretty clear that your wife does have a monoclonal m-spike in the ballpark of 0.7 g/dL. Does the most recent SPEP lab report indicate any uncertainty in this latest figure like the previous report did?
Secondly, are you saying that both the lambda and kappa free light chain values are high and out of range, along with the FLC ratio? What exactly are all those FLC values? If all three values are high, that "may" suggest renal impairment. See this table posted by Ron Harvot to understand what various combinations of FLC values mean:
https://myelomabeacon.org/forum/increase-in-free-light-chains-t5384.html#p31517
(Table also available here.)
A quick way to help verify if your wife's renal function is normal is to look see if her creatinine and eGFR values on the comprehensive metabolic panel are both in the normal range.
Lastly, it might be a good idea to get a new serum immunofixation test to verify her current isotype (e.g. IgG kappa, etc). Transplants can sometimes cause isotype switches, where the disease might switch from being something like IgG kappa to another combination such as IgG lambda. This is especially true in allo transplants. Transplants can also produce multiple M-spikes with different isotypes (e.g. you can have both IgG-kappa and IgG-lambda monoclonal protein where there was only type present before the transplant). Either of these things can change how your free light chain numbers behave. But you need a serum immunofixation test to tell you if these things may be occurring. Note that none of these phenomena are considered to be bad things.
Having said all this, it's important to remember that lots of things can come and go in the first few months post-transplant and various lab figures can appear a bit "whacky" as your wife's immune system is reconstituted and the donor's immune system is engrafted, all while dealing with GVHD. Her oncologist is best suited to comment on all these latest numbers, especially given that her body is still undergoing changes from the recent transplant.
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Possible conflict between SPEP & bone marrow results?
Thanks for the excellent explanation, Multibilly.
The test result indicates "spike, probably monoclonal in beta/gamma region(s)" I checked and all of the previous test results indicate "probably." Possibly, this is mostly an automated result but there is a Pathologist name at the end of the report.
Both her Kappa value and Lambda values are increasing.
Aug 24: Kappa, 0.99, Lambda 0.61, Ratio 1.62
Sep 22: Kappa 1.28, Lambda 0.87, Ratio 1.47
Sep 27: Kappa 2.17, Lambda 1.21, Ratio 1.79
Creatinine is 0.79 mg/dl
eGFR is >60 mL/min
The kidney function appears to be okay. Her total protein has declined to 6.6 last week. It was 7.4 on August 16.
The paraprotein increase seems to be inconsistent with the recent kappa-lambda ratios and the total protein change. I wonder if the September 27 ratio is correct as it is quite different from the previous results.
The test result indicates "spike, probably monoclonal in beta/gamma region(s)" I checked and all of the previous test results indicate "probably." Possibly, this is mostly an automated result but there is a Pathologist name at the end of the report.
Both her Kappa value and Lambda values are increasing.
Aug 24: Kappa, 0.99, Lambda 0.61, Ratio 1.62
Sep 22: Kappa 1.28, Lambda 0.87, Ratio 1.47
Sep 27: Kappa 2.17, Lambda 1.21, Ratio 1.79
Creatinine is 0.79 mg/dl
eGFR is >60 mL/min
The kidney function appears to be okay. Her total protein has declined to 6.6 last week. It was 7.4 on August 16.
The paraprotein increase seems to be inconsistent with the recent kappa-lambda ratios and the total protein change. I wonder if the September 27 ratio is correct as it is quite different from the previous results.
Re: Possible conflict between SPEP & bone marrow results?
Falcon,
To be clear, the latest lambda free light chain value is within range and is not "high" (i.e., above the normal range). Her kappa value is indeed above the normal range and is therefore "high". The free light chain ratio is simply the kappa value divided by the lambda value, which is 2.17/1.21 = 1.79 (which is also high and out of range). Free light chain ratios are not measured, but rather calculated from the measured kappa and lambda values.
I'm not a doctor, but it seems clear that both her M-spike and kappa free light chain values are increasing roughly in tandem. In other words, her "involved" monoclonal immunoglobulins (IgG heavy chain and kappa free light chain) are both increasing at the same time. But be clear that it's not a given that both of these will always rise or fall in harmony.
To be clear, the latest lambda free light chain value is within range and is not "high" (i.e., above the normal range). Her kappa value is indeed above the normal range and is therefore "high". The free light chain ratio is simply the kappa value divided by the lambda value, which is 2.17/1.21 = 1.79 (which is also high and out of range). Free light chain ratios are not measured, but rather calculated from the measured kappa and lambda values.
I'm not a doctor, but it seems clear that both her M-spike and kappa free light chain values are increasing roughly in tandem. In other words, her "involved" monoclonal immunoglobulins (IgG heavy chain and kappa free light chain) are both increasing at the same time. But be clear that it's not a given that both of these will always rise or fall in harmony.
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Possible conflict between SPEP & bone marrow results?
Maybe there are 2 things going on. One is the increase in the M protein, The other may be an inflammatory process related to some GVHD. She has been treated for GVHD. The immune response would have an effect of excess polyclonal kappa and lambda (I think). There is the M spike that is somehow differentiated from the polyclonal (in the result; I presume the level is measured independent of the polyclonal, or the serum immunofixation would reveal this), if I understand correctly. This increases the ratio.
Rechecked her results and in September of 2016 her bone marrow was <1% (p). In March of 2017 it was 1% (p). In June of 20'17, it was 2% (p). In May of 2016 (over a year ago), it was 3% (m). The bone marrow results have indicated polyclonal for just over a year.
Prior to her allogeneic transplant, her M was 0.29 and then the result was "HypoGam" at 100 days after the transplant. Just seems odd that the bone marrow is p and yet there is an M-spike.She is 100% donor cells as of June.
Rechecked her results and in September of 2016 her bone marrow was <1% (p). In March of 2017 it was 1% (p). In June of 20'17, it was 2% (p). In May of 2016 (over a year ago), it was 3% (m). The bone marrow results have indicated polyclonal for just over a year.
Prior to her allogeneic transplant, her M was 0.29 and then the result was "HypoGam" at 100 days after the transplant. Just seems odd that the bone marrow is p and yet there is an M-spike.She is 100% donor cells as of June.
Re: Possible conflict between SPEP & bone marrow results?
As I said before, lab figures can do peculiar things in the weeks and months post-transplant. At this point , I would suggest relying on the doctor's guidance rather than try to overanalyze all of these lab results on your own. Just my two cents.
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
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