Hi All,
Just thought I would start a thread on this topic...since we are really contaminating Ron's thread
on biking. I kinda think that is unfair, as he wanted to have a thread topic on something besides all this disease stuff.
Sorry Ron!!
Anyhooo...the news is when I when in to get Neupogen shots instructions, I was able to stop in clinic and ask my results for IR and MR...and they were NEGATIVE!!!
Hallelujiah!!
Additionally, I learned about another test which is even more sensitive than the IR it is called
PCR and can be down on peripheral blood (i.e. no BM aspirate needed) I was so happy to learn
about this as the molecular biologist explained that it is the most highly sensitive.
Soooo, I will be requesting this test. I understand that it requires a lot more work and technique.
Even so, the more ultra-sensitive the test..the better it is for me in terms of knowing the level of tumor contamination (LTC) or MRD remaining in my cells.
Interestingly, I also learned that all these cytogentic chromosomal aborrmalities are limited to the multiple myeloma cells, and if they are gone..so are those chromosomal abnormalities. I had always assumed that mutant chromosomes were global, had not grasped they were limited to the mutant multiple myeloma cells.
"The idea that myeloma-specific translocations are insufficient to produce a fully malignant phenotype is also supported by the observation that the frequency of translocations in monoclonal gammopathy of undetermined significance (MGUS) and myeloma is similar, with only a small number of MGUS patients progressing to myeloma. A possible exception is the low frequency of MGUS cases with a t(4;14), which seem to progress more rapidly to myeloma. In this context, the t(4;14) could be associated with a higher rate of genomic instability that might facilitate the acquisition of new genomic alterations leading more rapidly to myeloma."
http://bloodjournal.hematologylibrary.org/content/110/9/3112.full
Speaking to the molecular biologist was the highlight of my day and a real learning curve, his job entails designing oncologic agents. Quite interesting chat.
I am always amazed how God puts people in your path to help you..right when you need it.
God is always on time!!
Here is a paper on IR vs. sFC for those wanting to read more:
http://jco.ascopubs.org/content/29/12/1627.full
And here is a comparison analysis of PCR vs. IR:
"Although MRD evaluation by ASO-RQ-PCR is slightly more sensitive and specific than FCM, it is applicable in a lower proportion of multiple myeloma patients and is more time-consuming, while both techniques provide similar prognostic information."
http://www.haematologica.org/content/90/10/1365.short
http://www.exphem.org/article/S0301-472X(02)00794-4/abstract
MRD= minimal residual disease
FCM= Flow Cytometry
Everyone maynot want/need this level of ultra-sensitivity detection..but with all the good, bad, and ugly chromosomes I have...I definitely feel the need to go the extra mile and get this type data. Especially, since the molecularly biologist who happened to be a PhD also, recommended it.
In addition, he was a cancer survivor, and was back for monitoring.
On to harvesting...cGSF shots started tonight.
Forums
9 posts
• Page 1 of 1
Re: CR's vs. IR's vs. MR's..or MRD tests
Interestingly the Beacon reported on the use of PCR post ASCT:
"In ASCT, the patients’ own stem cells that were collected before high-dose chemotherapy are transplanted back into the patients. Most myeloma patients retain a small number of cancerous cells in their blood and bone marrow after ASCT. These cells are a major cause of relapse. At the same time, they are difficult to detect by most techniques because of their small number. They can, however, be detected by a sensitive biological technique known as polymerase chain reaction (PCR).
The study authors hypothesized that new agents such thalidomide, Revlimid (lenalidomide) and Velcade, may be effective in further reducing the number of tumor cells surviving in the marrow after ASCT to levels only observed with allogeneic stem cell transplantations. In allogeneic stem cell transplantations, patients receive bone marrow from a donor."
https://myelomabeacon.org/news/2010/04/06/velcade-thalidomide-dexamethasone-therapy-after-stem-cell-transplant-improves-response-in-multiple-myeloma-patients/
I found this interesting for a couple of reasons. One it seems that they are acknowledging that by using the PCR test they can improve the level of MRD to the levels of allogenic transplant. Two, to date allogenic transplant is the only procedure demonstrating a 'cure'. Third they gave these cycles post-ASCT.
So, the question I have is why then isn't PCR used to determine how many cycles of therapy a patient receives? Does a patient have to endure ASCT to meet this MRD level or do they simply need more cycles of triple combo chemo therapy?
Awhile back I pondered how was it determined to give 8 cycles?
https://myelomabeacon.org/forum/post2615.html#p2615
I suspect this is the length most likely to get the CR's that big pharma needs for FDA approval
however, it is not about the patient having a sustained or DOR that reflects MRD. I can also see that 8 cycles were likely least toxicity in 2010 with bortezomib and thalidomide making 8 optimum for side effects. Again, this is not focused on overalll survival or efficacy for patients.
Given, that there is such a large refractory/relapse population,perhaps, that is not optimum length therapy and PCR tests can be used to determine if more cycles of therapy are needed.
Now, this article from 2010 seems to focus more on the pharm mfgrs trying to push maintenance with lenalidomide...but perhaps what patients would benefit more greatly from is lenghtening the induction therapy based on PCR tests?
Having knowledge of MRD and how sensitive PCR tests, patients can be their own advocates and request continued therapy with less toxic agents like carfilzomib to reach the trace MRD levels comparable to allogenic transplants.
Who knows that just may be the way to achieve OS and even...dare I mention it...cures?
"In ASCT, the patients’ own stem cells that were collected before high-dose chemotherapy are transplanted back into the patients. Most myeloma patients retain a small number of cancerous cells in their blood and bone marrow after ASCT. These cells are a major cause of relapse. At the same time, they are difficult to detect by most techniques because of their small number. They can, however, be detected by a sensitive biological technique known as polymerase chain reaction (PCR).
The study authors hypothesized that new agents such thalidomide, Revlimid (lenalidomide) and Velcade, may be effective in further reducing the number of tumor cells surviving in the marrow after ASCT to levels only observed with allogeneic stem cell transplantations. In allogeneic stem cell transplantations, patients receive bone marrow from a donor."
https://myelomabeacon.org/news/2010/04/06/velcade-thalidomide-dexamethasone-therapy-after-stem-cell-transplant-improves-response-in-multiple-myeloma-patients/
I found this interesting for a couple of reasons. One it seems that they are acknowledging that by using the PCR test they can improve the level of MRD to the levels of allogenic transplant. Two, to date allogenic transplant is the only procedure demonstrating a 'cure'. Third they gave these cycles post-ASCT.
So, the question I have is why then isn't PCR used to determine how many cycles of therapy a patient receives? Does a patient have to endure ASCT to meet this MRD level or do they simply need more cycles of triple combo chemo therapy?
Awhile back I pondered how was it determined to give 8 cycles?
https://myelomabeacon.org/forum/post2615.html#p2615
I suspect this is the length most likely to get the CR's that big pharma needs for FDA approval
however, it is not about the patient having a sustained or DOR that reflects MRD. I can also see that 8 cycles were likely least toxicity in 2010 with bortezomib and thalidomide making 8 optimum for side effects. Again, this is not focused on overalll survival or efficacy for patients.
Given, that there is such a large refractory/relapse population,perhaps, that is not optimum length therapy and PCR tests can be used to determine if more cycles of therapy are needed.
Now, this article from 2010 seems to focus more on the pharm mfgrs trying to push maintenance with lenalidomide...but perhaps what patients would benefit more greatly from is lenghtening the induction therapy based on PCR tests?
Having knowledge of MRD and how sensitive PCR tests, patients can be their own advocates and request continued therapy with less toxic agents like carfilzomib to reach the trace MRD levels comparable to allogenic transplants.
Who knows that just may be the way to achieve OS and even...dare I mention it...cures?
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suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: CR's vs. IR's vs. MR's..or MRD tests
Looks like PCR was the traditional test used prior to 2008 and because it requires far more work they moved to MFC, and MFC picks up MRD in more folks than PCR?
"Traditionally, the polymerase chain reaction (PCR) method is used to evaluate MRD in myeloma patients. PCR is used to multiply small amounts of DNA, so that even traces of cancerous DNA can be detected. Though the method is highly sensitive, its applications are limited and the procedure is time-consuming.
The study of MFC suggests that it could be used to better predict outcomes in myeloma patients. In fact, MFC is more likely than PCR to successfully identify residual cancer cells. MFC labels the physical changes in these cells, which can be detected in 90 percent of myeloma patients. PCR labels DNA changes, which can be detected in only 75 percent of myeloma patients."
https://myelomabeacon.org/news/2008/11/19/new-technique-shows-improved-detection-of-tumor-cells-after-myeloma-treatment/
I am just wondering since PCR has greater sensitivity when it comes to DNA changes, which would be highly important for those with cytogenetic abnormalities..is it best for that subset of patients and those without cytogenetic abnormalities would MFC is sufficient?
Is this a test best for patients with chromosomal mutations i.e. 'high risk' patients and/ or 75% of patients?
MFC=multiparametric flow cytometry
"Traditionally, the polymerase chain reaction (PCR) method is used to evaluate MRD in myeloma patients. PCR is used to multiply small amounts of DNA, so that even traces of cancerous DNA can be detected. Though the method is highly sensitive, its applications are limited and the procedure is time-consuming.
The study of MFC suggests that it could be used to better predict outcomes in myeloma patients. In fact, MFC is more likely than PCR to successfully identify residual cancer cells. MFC labels the physical changes in these cells, which can be detected in 90 percent of myeloma patients. PCR labels DNA changes, which can be detected in only 75 percent of myeloma patients."
https://myelomabeacon.org/news/2008/11/19/new-technique-shows-improved-detection-of-tumor-cells-after-myeloma-treatment/
I am just wondering since PCR has greater sensitivity when it comes to DNA changes, which would be highly important for those with cytogenetic abnormalities..is it best for that subset of patients and those without cytogenetic abnormalities would MFC is sufficient?
Is this a test best for patients with chromosomal mutations i.e. 'high risk' patients and/ or 75% of patients?
MFC=multiparametric flow cytometry
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suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: CR's vs. IR's vs. MR's..or MRD tests
I think I may have answer.
Polymerase Chain Reaction
Polymerase chain reaction (PCR) is an extra-sensitive test that measures the presence of certain biomarkers in blood or bone marrow cells. It measures any remaining blood cancer cells not found by cytogenetic methods such as FISH. PCR is used to diagnose and check a patient's molecular response to treatment. PCR can detect a specific DNA abnormality or marker found in patients with certain blood cancers such as acute promyelocytic leukemia and chronic myeloid leukemia. PCR allows more sensitive follow-up of patients in remission and can help determine whether additional treatment is needed.
http://www.lls.org/diseaseinformation/managingyourcancer/newlydiagnosed/understandingdiagnosis/labimagingtests/bloodtests/
Polymerase Chain Reaction
Polymerase chain reaction (PCR) is an extra-sensitive test that measures the presence of certain biomarkers in blood or bone marrow cells. It measures any remaining blood cancer cells not found by cytogenetic methods such as FISH. PCR is used to diagnose and check a patient's molecular response to treatment. PCR can detect a specific DNA abnormality or marker found in patients with certain blood cancers such as acute promyelocytic leukemia and chronic myeloid leukemia. PCR allows more sensitive follow-up of patients in remission and can help determine whether additional treatment is needed.
http://www.lls.org/diseaseinformation/managingyourcancer/newlydiagnosed/understandingdiagnosis/labimagingtests/bloodtests/
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suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: CR's vs. IR's vs. MR's..or MRD tests
Suzierose
Thanks for your consideration on moving this discussion. The point of my thread is to discuss things to focus on besides the disease. As you noted the discussion turned back to the disease and I even got caught in it. That shows just how difficult it is to focus on something else when cancer is always looming in the background . It is the elephant in the room that can't be ignored.
Ron
Thanks for your consideration on moving this discussion. The point of my thread is to discuss things to focus on besides the disease. As you noted the discussion turned back to the disease and I even got caught in it. That shows just how difficult it is to focus on something else when cancer is always looming in the background . It is the elephant in the room that can't be ignored.
Ron
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Ron Harvot
Re: CR's vs. IR's vs. MR's..or MRD tests
Hi Ron,
No problem...you are more than welcome!
One other thing to consider when you want to post on a topic other than disease
is the Burgundy Cafe...it is listed under Forum Homes below the multiple myeloma discussion section as General Discussion..
I really liked your topic and enjoyed the thread.
No problem...you are more than welcome!
One other thing to consider when you want to post on a topic other than disease
is the Burgundy Cafe...it is listed under Forum Homes below the multiple myeloma discussion section as General Discussion..
I really liked your topic and enjoyed the thread.
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suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: CR's vs. IR's vs. MR's..or MRD tests
Dear Suzierose and Mark,
Thank you for moving the thread...I jumped in without having read the earlier pages on what the topic was supposed to be (so sorry, Ron!). I am still digesting all of these acronyms and explanations of tests, but you have helped immensely! Thank you, Mark, for the congratulations! We were waiting for the residual protein to disappear completely. I have had two BMB since the transplant that said "no evidence of myeloma" in the report, but I have no idea whether those extra tests were done (I doubt it, but will ask). My next BMB is not scheduled until August, on the one-year anniversary of my allo. What my doctor had been monitoring closely were minute spikes that she sensed were a result of the new immune system ramping up versus any active cancer, but she would not call it a CR until she had verified this with immunofixation testing.
I'm so happy for you that you don't have any gvh! I do have chronic gvh in my mouth, but it doesn't bother me much. I also have watery eyes, which others have said to be grateful for, as it's apparently much better than having dry eyes. My doctor doesn't want to treat the gvh at all, and is hopeful it will also increase the graft vs. myeloma effect. I did speak with her at length about DLIs, but she doesn't want me to have any yet. I can't remember if I told you before that my donor was a half-match, and that it was a tandem transplant (I had an auto SCT just three months prior) but I am also in a trial that reduced the duration of tacrolimus post-transplant, so I was pulled off it after three months. She is concerned that if I have a DLI at this time, it will increase the gvh, necessitating treatment, and she doesn't want any dexa treatment to suppress this new immune system.
Like you, I am greatly enjoying being off treatment! That alone is a tremendous gift, and I am so happy to hear that you are doing so well, too! Thanks for all the information you have shared with me. And Suzierose, you are right on about how God always provides the right information at the right time. His timing is indeed perfect!! Blessings, Dana
Thank you for moving the thread...I jumped in without having read the earlier pages on what the topic was supposed to be (so sorry, Ron!). I am still digesting all of these acronyms and explanations of tests, but you have helped immensely! Thank you, Mark, for the congratulations! We were waiting for the residual protein to disappear completely. I have had two BMB since the transplant that said "no evidence of myeloma" in the report, but I have no idea whether those extra tests were done (I doubt it, but will ask). My next BMB is not scheduled until August, on the one-year anniversary of my allo. What my doctor had been monitoring closely were minute spikes that she sensed were a result of the new immune system ramping up versus any active cancer, but she would not call it a CR until she had verified this with immunofixation testing.
I'm so happy for you that you don't have any gvh! I do have chronic gvh in my mouth, but it doesn't bother me much. I also have watery eyes, which others have said to be grateful for, as it's apparently much better than having dry eyes. My doctor doesn't want to treat the gvh at all, and is hopeful it will also increase the graft vs. myeloma effect. I did speak with her at length about DLIs, but she doesn't want me to have any yet. I can't remember if I told you before that my donor was a half-match, and that it was a tandem transplant (I had an auto SCT just three months prior) but I am also in a trial that reduced the duration of tacrolimus post-transplant, so I was pulled off it after three months. She is concerned that if I have a DLI at this time, it will increase the gvh, necessitating treatment, and she doesn't want any dexa treatment to suppress this new immune system.
Like you, I am greatly enjoying being off treatment! That alone is a tremendous gift, and I am so happy to hear that you are doing so well, too! Thanks for all the information you have shared with me. And Suzierose, you are right on about how God always provides the right information at the right time. His timing is indeed perfect!! Blessings, Dana
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Dana - Name: Dana
- Who do you know with myeloma?: myself
- When were you/they diagnosed?: 2009
- Age at diagnosis: 43
Re: CR's vs. IR's vs. MR's..or MRD tests
Chromosomal aberrations, such as translocations or inversions, described for a growing number of malignancies, are now widely used to detect tumor cells by polymerase chain reaction (PCR). However, in multiple myeloma (multiple myeloma), no such ubiquitous PCR marker exists. Therefore, other means have been established to distinguish myeloma cells from normal cells. Because the plasma cells of a myeloma clone share an identical rearranged immunoglobulin gene sequence, it is possible to detect malignant cells with PCR primers specific for the VDJ rearrangement of the heavy chain of each myeloma clone. The sensitivity and specificity of this method, named allele-specific oligonucleotide (ASO) PCR, even with low proportions of malignant cells, has been proven (1).
http://www.springerprotocols.com/Abstract/doi/10.1385/1-59259-384-4:185#CR1
http://www.springerprotocols.com/Abstract/doi/10.1385/1-59259-384-4:185#CR1
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suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: CR's vs. IR's vs. MR's..or MRD tests
"Although allele-specific oligonucleotide real-time polymerase chain reaction is more sensitive than multiparametric flow cytometry (MFC) for MRD analysis, it is more labor-intensive and time-consuming and less readily available. The patchy nature of residual plasma cell (PC) infiltrate after therapy and hemodilution of bone marrow aspirates may undermine the quantification of PCs with respect to overall bone marrow cellularity. This may result in false-negative MRD flow cytometric results when compared with immunofixation (IFx) or allele-specific oligonucleotide real-time polymerase chain reaction."
http://ajcp.ascpjournals.org/content/132/5/728.full
http://ajcp.ascpjournals.org/content/132/5/728.full
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suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
9 posts
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