My wife had an allogeneic stem cell transplant 17 months ago and her bone marrow is clean (no plasma cells and P for polyclonal) and has been for since the transplant.. Bone marrow test results are still good.
Even though the bone marrow is fine, she continues to have paraprotein (M-spike) in her blood (coming from the bone), however, and had to be treated last December due to 2 bone plasmacytomas. The treatment worked very well, but she continues to have a residual level of paraprotein in the blood, and now, it appears, 4 month later, her kappa value is starting to increase, although still within range. The paraprotein in the blood declined, but there is still an amount remaining.
Does anyone know what this sort of situation means, and how it is best treated?
We thought that if the allogeneic transplant worked, it would also resolve any paraprotein in the blood. Does this process take an extended period of time to fully impact the bone, or is this process (bone plasmacytomas) somehow disconnected and independent from the condition of the bone marrow?
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Re: Bone marrow clear post allo, but still have M-spike
Hello Falcon,
So, apparently it's not unusual for myeloma patients who have undergone an allogeneic transplant to develop "secondary MGUS." This is usually defined to be the appearance of an M-spike or monoclonal free light chains that are different from those the patient originally had at diagnosis.
So, let's say you're diagnosed with IgG kappa myeloma. You undergo an allo transplant, and after the transplant you develop a low-level M-spike that is IgA kappa. That most likely would be classified as secondary MGUS.
In the study I list below, almost half the myeloma patients who underwent an allogeneic transplant developed secondary MGUS, usually within six months of the transplant, but sometimes up to a year or two later.
More importantly, those who developed secondary MGUS had a much better prognosis than those who did not. This is something that has been seen, in some (but not all) studies investigating secondary MGUS in patients undergoing autologous stem cell transplants.
I'm not sure, though, whether what you're seeing in your wife's case is really secondary MGUS. One way to check would be the type of monoclonal proteins she has now versus what she had before the transplant. Are they the same type (IgG lambda, IgA kappa, etc.), or is the type different now?
Perhaps of greater importance is the fact that your wife developed bone plasmacytomas after her transplant. To me (and I'm not a doctor), this suggests that the transplant did not completely wipe out her myeloma, especially if it's certain that the plasmacytomas developed after her transplant.
You'll have to check this interpretation with her doctors, but if it's true, the doctors probably will be figuring out ways to use radiation, myeloma drug treatments, and perhaps even donor lymphocyte infusions to beat back the recurring myeloma.
That's all that I can think of on the subject. Please let us know if you find out anything more, and best of luck to you and (especially) your wife.
Reference:
Schmitz, MF, et al, "Secondary Monoclonal Gammopathy Of Undetermined Significance After Allogeneic Stem Cell Transplantation In Multiple Myeloma," Haematologica, Dec 2014 (full text of article)
Abstract:
In the course of multiple myeloma, patients may develop a M-protein band different from the original: secondary monoclonal gammopathy of undetermined significance. In this retrospective single center analysis, we describe the occurrence and clinical relevance of secondary monoclonal gammopathy of undetermined significance after allogeneic stem cell transplantation (post-transplant monoclonal gammopathy of undetermined significance). A total of 138 patients who had undergone 139 allogeneic stem cell transplantations (39.6% in the upfront setting and 60.4% for relapsed multiple myeloma) were included in the study. Sixty-seven (48.2%) patients developed secondary monoclonal gammopathy of undetermined significance, after a median latency of 6.9 months. Secondary monoclonal gammopathy of undetermined significance occurred more often in patients who achieved at least very good partial response after allogeneic stem cell transplantation, compared to partial response or less (54.8% vs. 26.5%; P=0.005). The incidence was also higher in the upfront setting as compared to relapsed disease, or with a sibling donor compared to matched unrelated donor, but less often after T-cell depletion. Importantly, development of post-transplant monoclonal gammopathy of undetermined significance as a time-dependent variable independently predicted for superior progression-free and overall survival (median progression-free survival 37.5 vs. 6.3 months, P<0.001; median overall survival 115.3 vs. 31.0 months, P=0.004). Clinicians should be aware of the benign nature of this phenomenon, and secondary monoclonal gammopathy of undetermined significance should not be confused with relapse or progression of disease. (Trial registered with trialregister.nl; HOVON 108: NTR 2958.)
So, apparently it's not unusual for myeloma patients who have undergone an allogeneic transplant to develop "secondary MGUS." This is usually defined to be the appearance of an M-spike or monoclonal free light chains that are different from those the patient originally had at diagnosis.
So, let's say you're diagnosed with IgG kappa myeloma. You undergo an allo transplant, and after the transplant you develop a low-level M-spike that is IgA kappa. That most likely would be classified as secondary MGUS.
In the study I list below, almost half the myeloma patients who underwent an allogeneic transplant developed secondary MGUS, usually within six months of the transplant, but sometimes up to a year or two later.
More importantly, those who developed secondary MGUS had a much better prognosis than those who did not. This is something that has been seen, in some (but not all) studies investigating secondary MGUS in patients undergoing autologous stem cell transplants.
I'm not sure, though, whether what you're seeing in your wife's case is really secondary MGUS. One way to check would be the type of monoclonal proteins she has now versus what she had before the transplant. Are they the same type (IgG lambda, IgA kappa, etc.), or is the type different now?
Perhaps of greater importance is the fact that your wife developed bone plasmacytomas after her transplant. To me (and I'm not a doctor), this suggests that the transplant did not completely wipe out her myeloma, especially if it's certain that the plasmacytomas developed after her transplant.
You'll have to check this interpretation with her doctors, but if it's true, the doctors probably will be figuring out ways to use radiation, myeloma drug treatments, and perhaps even donor lymphocyte infusions to beat back the recurring myeloma.
That's all that I can think of on the subject. Please let us know if you find out anything more, and best of luck to you and (especially) your wife.
Reference:
Schmitz, MF, et al, "Secondary Monoclonal Gammopathy Of Undetermined Significance After Allogeneic Stem Cell Transplantation In Multiple Myeloma," Haematologica, Dec 2014 (full text of article)
Abstract:
In the course of multiple myeloma, patients may develop a M-protein band different from the original: secondary monoclonal gammopathy of undetermined significance. In this retrospective single center analysis, we describe the occurrence and clinical relevance of secondary monoclonal gammopathy of undetermined significance after allogeneic stem cell transplantation (post-transplant monoclonal gammopathy of undetermined significance). A total of 138 patients who had undergone 139 allogeneic stem cell transplantations (39.6% in the upfront setting and 60.4% for relapsed multiple myeloma) were included in the study. Sixty-seven (48.2%) patients developed secondary monoclonal gammopathy of undetermined significance, after a median latency of 6.9 months. Secondary monoclonal gammopathy of undetermined significance occurred more often in patients who achieved at least very good partial response after allogeneic stem cell transplantation, compared to partial response or less (54.8% vs. 26.5%; P=0.005). The incidence was also higher in the upfront setting as compared to relapsed disease, or with a sibling donor compared to matched unrelated donor, but less often after T-cell depletion. Importantly, development of post-transplant monoclonal gammopathy of undetermined significance as a time-dependent variable independently predicted for superior progression-free and overall survival (median progression-free survival 37.5 vs. 6.3 months, P<0.001; median overall survival 115.3 vs. 31.0 months, P=0.004). Clinicians should be aware of the benign nature of this phenomenon, and secondary monoclonal gammopathy of undetermined significance should not be confused with relapse or progression of disease. (Trial registered with trialregister.nl; HOVON 108: NTR 2958.)
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Jonah
Re: Bone marrow clear post allo, but still have M-spike
Hi Falcon,
I am not sure what you meant by using the word "worked' in the first sentence of your last paragraph. Did you mean that she engrafted and has 100% donor chimerism? If so, that would not mean that she could not relapse, particularly with extramedullary disease / plasmacytoma if the patient was in less than complete response or had relapsed disease prior to doing the transplant. You will see this type of thing discussed in medical literature; for example:
'We had three cases [that received allogeneic reduced-intensity stem cell transplant (RIST) ... All of three cases relapsing or progressing after RIST showed disease type of plasmacytoma without plasma cells in the bone marrow. That may be because conditioning regimen doesn't include total body irradiation, or GVM is ineffective in plasmacytoma, but effective in bone marrow. Here, we report clinical course of these three cases with some consideration."
From:
Sugimoto, Y, et al., "Multiple myeloma relapsed or progressed as plasmacytoma after allogeneic reduced-intensity stem cell transplantation: report of three cases" (in Japanese), Rinsho Ketsueki. 2009 Apr;50(4):289-94 (abstract in Japanese).
Here is another paper discussing extramedullary relapses after allogeneic transplant if interested in reading, which notes: "The predictive value of serial chimerism analysis for heralding relapse was limited because of the high frequency of extramedullary relapses after allo-SCT.":
Rasche, L., et al, "Allogeneic Hematopoietic Cell Transplantation in Multiple Myeloma: Focus on Longitudinal Assessment of Donor Chimerism, Extramedullary Disease, and High-Risk Cytogenetic Features," Biology of Blood and Marrow Transplantation, Nov 2016 (full text of article)
I am certainly not saying your wife is relapsing, but it is a possibility. It could be that imaging studies would give more information than a bone marrow biopsy at this point. I know in my own case I have not done a bone marrow biopsy in about 4 years and we are not planning on doing any more, but they still like me doing imaging studies every 2 years. Back in the first few years after my allogeneic transplant, I had my kappa value (I had IgG kappa) bounce around in the normal range. Like with other tests, you should look for trends as opposed to month-to-month gyrations.
Best of luck moving forward and hopefully this is just some type of secondary MGUS.
Mark
I am not sure what you meant by using the word "worked' in the first sentence of your last paragraph. Did you mean that she engrafted and has 100% donor chimerism? If so, that would not mean that she could not relapse, particularly with extramedullary disease / plasmacytoma if the patient was in less than complete response or had relapsed disease prior to doing the transplant. You will see this type of thing discussed in medical literature; for example:
'We had three cases [that received allogeneic reduced-intensity stem cell transplant (RIST) ... All of three cases relapsing or progressing after RIST showed disease type of plasmacytoma without plasma cells in the bone marrow. That may be because conditioning regimen doesn't include total body irradiation, or GVM is ineffective in plasmacytoma, but effective in bone marrow. Here, we report clinical course of these three cases with some consideration."
From:
Sugimoto, Y, et al., "Multiple myeloma relapsed or progressed as plasmacytoma after allogeneic reduced-intensity stem cell transplantation: report of three cases" (in Japanese), Rinsho Ketsueki. 2009 Apr;50(4):289-94 (abstract in Japanese).
Here is another paper discussing extramedullary relapses after allogeneic transplant if interested in reading, which notes: "The predictive value of serial chimerism analysis for heralding relapse was limited because of the high frequency of extramedullary relapses after allo-SCT.":
Rasche, L., et al, "Allogeneic Hematopoietic Cell Transplantation in Multiple Myeloma: Focus on Longitudinal Assessment of Donor Chimerism, Extramedullary Disease, and High-Risk Cytogenetic Features," Biology of Blood and Marrow Transplantation, Nov 2016 (full text of article)
I am certainly not saying your wife is relapsing, but it is a possibility. It could be that imaging studies would give more information than a bone marrow biopsy at this point. I know in my own case I have not done a bone marrow biopsy in about 4 years and we are not planning on doing any more, but they still like me doing imaging studies every 2 years. Back in the first few years after my allogeneic transplant, I had my kappa value (I had IgG kappa) bounce around in the normal range. Like with other tests, you should look for trends as opposed to month-to-month gyrations.
Best of luck moving forward and hopefully this is just some type of secondary MGUS.
Mark
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Mark11
Re: Bone marrow clear post allo, but still have M-spike
She has had at least 3, possibly 4, bone marrow biopsies since her allogeneic transplant and each result noted 100% chimerism and the cells are polyclonal. The percent polyclonal has increased. Her type has remained as IgG kappa. She had a donor lymphocyte infusion (DLI) in February and they are about to start her on Darzalex as maintenance. The white blood count and platelets have remained low.
Thank you for the comments and best of luck to you as well!
Thank you for the comments and best of luck to you as well!
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