Hi everyone,
I'm being tested for multiple myeloma / MGUS / amyloidosis. Thus far most of my tests have been good (i.e., no M-spike on serum or 24-hour electrophoresis and no monoclonality detected on serum or 24 hour immunofixation). However, my serum free light chain test came back abnormal.
Free Kappa Lt Chains,S: 8.77 mg/L (3.30 - 19.40)
Free Lambda Lt Chains,S: 3.80 mg/L Low (5.71 - 26.30)
Kappa/Lambda Ratio,S: 2.31 High (0.26 - 1.65)
According to the interpretive chart that accompanies the test that I'm sure most of you are familiar with, this is apparently consistent with a monoclonal gammopathy with bone marrow suppression. Interestingly, however, I know pretty definitively that my bone marrow is not suppressed (CBC 100% normal) so I'm wondering how definitive those results are.
Despite what the chart says, I've checked with several doctors and all have said that these types of conditions were unlikely, despite what the interpretive chart says, given that the ratio is skewed due to low rather than high levels and that the rest of my labwork was ok.
So my question is if that interpretive chart is not definitive, what kinds of things could be causing abnormal results such as these?
I've read one research study on marathon runners that sought to compare pre-race and post-race free light chain results to determine the impact of exercise on free light chain levels.
Interestingly, a full 12% of the individuals had to be excluded from the study because their free light chain ratios were abnormal even before engaging in exercise, and obviously it's not likely that 12% of healthy marathon runners have a monoclonal disorder. The study also showed that immediately after the race, an additional 13% of the individuals left over (i.e., those who weren't excluded from the study previously due to a pre-race abnormal ratio) demonstrated an abnormal ratio, seemingly confirming that exercise can have a significant impact on FCL levels.
Now, I'm no marathon runner, but I am an avid weightlifter. Does it seem plausible that vigorous weightlifting several times per week could lead to abnormalities?
I had lifted weights approximately 24 hours before having my blood drawn for the test, which seems like it should be unlikely to cause any abnormalities, since the 'life cycle' of free light chains is so short (a matter of hours), but the study I mentioned clearly demonstrated a far increased incidence of abnormal free light chain ratios in endurance athletes even before they participated in the race, which seems to suggest that regular exercise could have some kind of chronic effect.
Does anyone have any thoughts on these matters, or can anyone think of any other causes of abnormal free light chain ratios?
Forums
Re: Exercise and serum free light chain test results
Hi btdyq5,
First off, the chart you made reference to is only for general information purposes and is certainly not to be taken as gospel. Second, one test is not normally useful; a series is much more useful to see a trend. Third, your numbers are all fairly good and not that far out of the normal range.
With respect to exercise, that may be possible, but marathon runners and cyclists are doing massive amounts of endurance work. I am a bicycle rider and also do a lot of long endurance training. My son is a weight lifter like you, but his exercises are short-burst, explosive-type work, not endurance. Not sure if they translate the same in the blood work, but interesting nevertheless.
What made you go to get tested for multiple myeloma in the first place? Did they do a bone scan or bone marrow biopsy?
First off, the chart you made reference to is only for general information purposes and is certainly not to be taken as gospel. Second, one test is not normally useful; a series is much more useful to see a trend. Third, your numbers are all fairly good and not that far out of the normal range.
With respect to exercise, that may be possible, but marathon runners and cyclists are doing massive amounts of endurance work. I am a bicycle rider and also do a lot of long endurance training. My son is a weight lifter like you, but his exercises are short-burst, explosive-type work, not endurance. Not sure if they translate the same in the blood work, but interesting nevertheless.
What made you go to get tested for multiple myeloma in the first place? Did they do a bone scan or bone marrow biopsy?
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Ron Harvot - Name: Ron Harvot
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: Feb 2009
- Age at diagnosis: 56
Re: Exercise and serum free light chain test results
Hi Ron,
Thank you for your response.
I'm being tested for multiple myeloma / MGUS / amyloidosis because I began developing petechiae out of nowhere about 8 months ago (which is still ongoing), which led to an adult-age diagnosis of von Willebrand disease. This is a relatively mild bleeding disorder that is usually hereditary and if so nothing to worry about. It's much more concerning if it shows up later in life because, although it's possible for it to be hereditary but just lay dormant for decades, in many cases it is 'acquired' secondary to a much more problematic condition, of which monoclonal disorders are at the top of the list.
Besides the petechiae, my symptoms include very intermittent tingling in hands / feet, back pain (although MRI revealed only a large herniated disc – no fractures or lytic lesions), and intermittent pain in ribs, hips, and thighs that I believe might be bone pain.
Thus far my docs don't seem especially concerned, as my serum / urine electrophoresis and immunofixation tests came back negative, but I remain very concerned about the serum free light chain results having an abnormal ratio. I stopped working out 10 days ago and actually just had my blood draw for the test again today in hopes that maybe it was a fluke.
If I may ask, when you say my numbers are fairly good and not far out of the normal range, do you mean fairly good for a multiple myeloma / amyloidosis patient, or fairly good as in these results possibly don't point to one of these diseases?
Thank you!
Thank you for your response.
I'm being tested for multiple myeloma / MGUS / amyloidosis because I began developing petechiae out of nowhere about 8 months ago (which is still ongoing), which led to an adult-age diagnosis of von Willebrand disease. This is a relatively mild bleeding disorder that is usually hereditary and if so nothing to worry about. It's much more concerning if it shows up later in life because, although it's possible for it to be hereditary but just lay dormant for decades, in many cases it is 'acquired' secondary to a much more problematic condition, of which monoclonal disorders are at the top of the list.
Besides the petechiae, my symptoms include very intermittent tingling in hands / feet, back pain (although MRI revealed only a large herniated disc – no fractures or lytic lesions), and intermittent pain in ribs, hips, and thighs that I believe might be bone pain.
Thus far my docs don't seem especially concerned, as my serum / urine electrophoresis and immunofixation tests came back negative, but I remain very concerned about the serum free light chain results having an abnormal ratio. I stopped working out 10 days ago and actually just had my blood draw for the test again today in hopes that maybe it was a fluke.
If I may ask, when you say my numbers are fairly good and not far out of the normal range, do you mean fairly good for a multiple myeloma / amyloidosis patient, or fairly good as in these results possibly don't point to one of these diseases?
Thank you!
Re: Exercise and serum free light chain test results
btdyq5,
When I say your numbers are fairly good,I am referring to the serum free light chain test results. The ratio is barely over the limit and the kappa level, which would be the dominant ("involved") light chain, is in range. Your ratio is out of the range only because your lambda free light chain level is slightly below normal.
The new standard for an initial diagnosis of "symptomatic" multiple myeloma (myeloma which is advanced enough to require treatment) is for the ratio of the dominant free light chain to non-dominant free light chain (involved / uninvolved) to be 100 or greater. Anything less than that does not amount to a diagnosis of multiple myeloma that would call for beginning treatment unless you had one of the "CRAB" symptoms, which you do not.
I don't think you have smoldering or even MGUS as this point, as none of your other tests point in that direction.
Good luck and keep pumping iron!
When I say your numbers are fairly good,I am referring to the serum free light chain test results. The ratio is barely over the limit and the kappa level, which would be the dominant ("involved") light chain, is in range. Your ratio is out of the range only because your lambda free light chain level is slightly below normal.
The new standard for an initial diagnosis of "symptomatic" multiple myeloma (myeloma which is advanced enough to require treatment) is for the ratio of the dominant free light chain to non-dominant free light chain (involved / uninvolved) to be 100 or greater. Anything less than that does not amount to a diagnosis of multiple myeloma that would call for beginning treatment unless you had one of the "CRAB" symptoms, which you do not.
I don't think you have smoldering or even MGUS as this point, as none of your other tests point in that direction.
Good luck and keep pumping iron!
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Ron Harvot - Name: Ron Harvot
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: Feb 2009
- Age at diagnosis: 56
Re: Exercise and serum free light chain test results
Thank you very much for the information! It is much appreciated!
Re: Exercise and serum free light chain test results
Hi,
Thanks for your post and question, btdyq5. You prompted me to look at something I've been wondering about for a few months.
I'm a runner, currently doing Revlimid maintenance, and I'm in complete response (CR) and minimal residual disease (MRD) negative as of my last bone marrow biopsy in August, 2015.
But my kappa / lambda ratio bounces around, sometimes normal, sometimes as high as a little over 6 in the past year. My myeloma specialist is not worried about the ratio at this time because there is no consistent pattern to it.
Anecdotally, though, it seemed to me that it was more likely to be high on days that I ran before being tested. So I went back and compared my kappa / lambda ratio to the distance I ran on the day of the lab test, the distance on the day before the lab test, and the sum of the two days' running distance for the period from April 1, 2015 to June 8, 2016. I was tested every 4 weeks during that time. (I picked April 1, 2015 as the starting date because I started running again after a partially torn Achilles tendon about a month before that.) My daily mileage during the period varied from 0 to 9 miles. My hypothesis was that the higher the distance, the higher the kappa / lambda ratio would be.
But my hypothesis is debunked. The correlation coefficients for day before distance, day of distance, and sum of both days' distance compared to kappa / lambda ratio were 0.22, 0.29, and 0.34, respectively. All of those are very weak correlations.
Oh well. It would have been nice if this hypothesis had worked out as a decent explanation for my variable kappa / lambda ratio. I have been told that both the kappa and lambda free light chain measurements can vary as much as 30% from day to day just under normal conditions. So I'm sure that some of the variability in my kappa / lambda ratio is due to that.
For your case, I agree with Ron's comments - I don't think you should be too concerned.
One favor - do you have a reference for the marathon runners' free light chains paper that you mentioned?
Thanks,
Mike
Thanks for your post and question, btdyq5. You prompted me to look at something I've been wondering about for a few months.
I'm a runner, currently doing Revlimid maintenance, and I'm in complete response (CR) and minimal residual disease (MRD) negative as of my last bone marrow biopsy in August, 2015.
But my kappa / lambda ratio bounces around, sometimes normal, sometimes as high as a little over 6 in the past year. My myeloma specialist is not worried about the ratio at this time because there is no consistent pattern to it.
Anecdotally, though, it seemed to me that it was more likely to be high on days that I ran before being tested. So I went back and compared my kappa / lambda ratio to the distance I ran on the day of the lab test, the distance on the day before the lab test, and the sum of the two days' running distance for the period from April 1, 2015 to June 8, 2016. I was tested every 4 weeks during that time. (I picked April 1, 2015 as the starting date because I started running again after a partially torn Achilles tendon about a month before that.) My daily mileage during the period varied from 0 to 9 miles. My hypothesis was that the higher the distance, the higher the kappa / lambda ratio would be.
But my hypothesis is debunked. The correlation coefficients for day before distance, day of distance, and sum of both days' distance compared to kappa / lambda ratio were 0.22, 0.29, and 0.34, respectively. All of those are very weak correlations.
Oh well. It would have been nice if this hypothesis had worked out as a decent explanation for my variable kappa / lambda ratio. I have been told that both the kappa and lambda free light chain measurements can vary as much as 30% from day to day just under normal conditions. So I'm sure that some of the variability in my kappa / lambda ratio is due to that.
For your case, I agree with Ron's comments - I don't think you should be too concerned.
One favor - do you have a reference for the marathon runners' free light chains paper that you mentioned?
Thanks,
Mike
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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: Exercise and serum free light chain test results
Hey Mike,
Interesting test. Not sure if the following article was ever posted on this forum or not, but it makes a case for endurance exercise to lower free light chain levels.
Heaney, J.L.J., et al, "Serum free light chains are reduced in endurance trained older adults: Evidence that exercise training may reduce basal inflammation in older adults," Experimental Gerontology, May 2016 (link to abstract)
Abstract:
Traditionally, free light chains (FLCs) are used as key serum biomarkers in the diagnosis and monitoring of plasma cell malignancies, but polyclonal FLCs can also be used as an accurate real-time indicator of immune-activation and inflammation. The primary aim of the present study was to assess the effects of exercise training status on serum FLCs in older adults, and secondly, to examine if training status moderated serum FLC responses to acute exercise. Kappa and lambda serum FLC levels were measured in 45 healthy older adults (aged ≥60years) who were either sedentary, physically active or endurance trained. FLCs were measured at baseline and in response to an acute bout of submaximal exercise. The endurance trained group had significantly lower levels of kappa and lambda serum FLCs compared with physically active or sedentary elderly adults; these effects were independent of age, BMI and renal function. There was no significant difference in whole immunoglobulins between groups. Exercise training status had no effect on serum FLC responses to acute exercise, which were marginal. In conclusion, endurance training was associated with lower FLC levels compared with less physically active individuals. These findings suggest that long-term endurance training may be beneficial in reducing basal inflammation in older adults as well as elevated FLCs present in inflammatory and autoimmune conditions, often associated with ageing. FLCs may serve as a useful biomarker for monitoring the efficacy of exercise intervention studies in healthy and clinical populations.
Interesting test. Not sure if the following article was ever posted on this forum or not, but it makes a case for endurance exercise to lower free light chain levels.
Heaney, J.L.J., et al, "Serum free light chains are reduced in endurance trained older adults: Evidence that exercise training may reduce basal inflammation in older adults," Experimental Gerontology, May 2016 (link to abstract)
Abstract:
Traditionally, free light chains (FLCs) are used as key serum biomarkers in the diagnosis and monitoring of plasma cell malignancies, but polyclonal FLCs can also be used as an accurate real-time indicator of immune-activation and inflammation. The primary aim of the present study was to assess the effects of exercise training status on serum FLCs in older adults, and secondly, to examine if training status moderated serum FLC responses to acute exercise. Kappa and lambda serum FLC levels were measured in 45 healthy older adults (aged ≥60years) who were either sedentary, physically active or endurance trained. FLCs were measured at baseline and in response to an acute bout of submaximal exercise. The endurance trained group had significantly lower levels of kappa and lambda serum FLCs compared with physically active or sedentary elderly adults; these effects were independent of age, BMI and renal function. There was no significant difference in whole immunoglobulins between groups. Exercise training status had no effect on serum FLC responses to acute exercise, which were marginal. In conclusion, endurance training was associated with lower FLC levels compared with less physically active individuals. These findings suggest that long-term endurance training may be beneficial in reducing basal inflammation in older adults as well as elevated FLCs present in inflammatory and autoimmune conditions, often associated with ageing. FLCs may serve as a useful biomarker for monitoring the efficacy of exercise intervention studies in healthy and clinical populations.
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Exercise and serum free light chain test results
I think this is the article about the impact of marathon running on FLC test results:
Campbell, JP, et al, "Assessment of serum free light chain levels in healthy adults immediately after marathon running", Clinical Chemistry and Laboratory Medicine, March 2016 (abstract)
According to the article abstract, the impact of marathon running on the FLC results is due to reduced kidney function that often occurs during marathon running. This elevates the kappa FLC result and therefore the kappa/lambda ratio.
As many people here in the forum know, the "normal" range for the kappa/lambda has a higher upper limit for patients with impaired renal function. Here are the two "normal" ranges for the ratio:
Kappa/lambda ratio "normal" range, patients with normal kidney function: 0.26 - 1.65
Kappa/lambda ratio "normal" range, patients with impaired kidney function: 0.37 - 3.10
Cheers!
Campbell, JP, et al, "Assessment of serum free light chain levels in healthy adults immediately after marathon running", Clinical Chemistry and Laboratory Medicine, March 2016 (abstract)
According to the article abstract, the impact of marathon running on the FLC results is due to reduced kidney function that often occurs during marathon running. This elevates the kappa FLC result and therefore the kappa/lambda ratio.
As many people here in the forum know, the "normal" range for the kappa/lambda has a higher upper limit for patients with impaired renal function. Here are the two "normal" ranges for the ratio:
Kappa/lambda ratio "normal" range, patients with normal kidney function: 0.26 - 1.65
Kappa/lambda ratio "normal" range, patients with impaired kidney function: 0.37 - 3.10
Cheers!
Re: Exercise and serum free light chain test results
Mike B and Ian:
That is in fact the article I was referring to, and that makes sense that temporary reductions in kidney function stemming from marathon training could increase kappa. I found this interesting because a sizable percentage of the would-be participants had to be excluded from the study because they had abnormal ratios even before the race, suggesting more of a chronic effect.
Given that I'm still in the process of diagnosis (or hopefully NO diagnosis) for amyloidosis or one of the monoclonal protein disorders, and with my only abnormalities being mildly low IgG, mildly high IgA, and an elevated kappa / lambda ratio (2.52 upon follow up testing) due to low lambda (3.66) and normal kappa (9.24), I was hoping against hope that perhaps regular weight training could possibly induce a similar effect, but thus far I'm not seeing too much evidence for this idea.
That is in fact the article I was referring to, and that makes sense that temporary reductions in kidney function stemming from marathon training could increase kappa. I found this interesting because a sizable percentage of the would-be participants had to be excluded from the study because they had abnormal ratios even before the race, suggesting more of a chronic effect.
Given that I'm still in the process of diagnosis (or hopefully NO diagnosis) for amyloidosis or one of the monoclonal protein disorders, and with my only abnormalities being mildly low IgG, mildly high IgA, and an elevated kappa / lambda ratio (2.52 upon follow up testing) due to low lambda (3.66) and normal kappa (9.24), I was hoping against hope that perhaps regular weight training could possibly induce a similar effect, but thus far I'm not seeing too much evidence for this idea.
Re: Exercise and serum free light chain test results
One common attribute of long distance cycling in warm/hot weather is that you consume a lot of fluids but do not urinate much. Also when you do urinate it is often dark. That points to dehydration. Yesterday, for example I did a 55 mile ride. I live in North Texas so it gets hot this time of year. When I started at 7:30 am the temp was already 82F. When I finished around 11:00am the temp was already in the low 90s. I consumed 3 20oz bottles of fluid that contained a mixture of water and electrolyte powder. I did not have an urge to urinate through out the ride. Marathon runners experience this as well.
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Ron Harvot - Name: Ron Harvot
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: Feb 2009
- Age at diagnosis: 56
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