What is generally more likely to cause a relapse after ASCT or a bad response to an ASCT - do the collected stem cells, contaminated with myeloma cancer cells, rather cause a relapse or a bad response or does the residual disease (myeloma cells) in the body/bone marrow, which is not completely wiped out by the high-dose melphalan during ASCT, cause a relapse after ASCT or a bad response to an ASCT? Which of these two factors is of higher importance?
Were there any studies that examined the reason for a relapse or a bad outcome within this context?
Thanks and kind regards,
Jason
Forums
6 posts
• Page 1 of 1
Re: "Contaminated" stem cells vs. residual disease in the bo
Hi Jason,
I believe the experts think that it is what the melphalan does not kill in the body as opposed to the graft being contaminated.
"Relapsed disease remains a major obstacle following autologous haematopoietic SCT (HSCT) for non-Hodgkin's lymphoma (NHL) and multiple myeloma (multiple myeloma). Studies regarding the importance of detectable tumour cells in PBSC collections have been inconclusive. Patients undergoing autologous HSCT for NHL and multiple myeloma between 2001 and 2006 were enrolled (n=158). PBSC grafts were assessed for clonal IgH CDR3 gene rearrangements using qualitative semi-nested PCR. In comparison to patients with PCR-positive PBSC grafts, patients negative for detectable disease had no improvement in overall survival (OS) or PFS for multiple myeloma (P=0.91 and 0.91) or NHL (P=0.82 and 0.85). Further, no significant difference in OS was observed between patients with PCR-positive compared with PCR-negative PBSC grafts with aggressive NHL histology (P=0.74) or indolent disease (P=0.29). Patients with contaminating tumour cells in autologous PBSCs do not have worsened OS or PFS in multiple myeloma or NHL. Tumour cells detected by sensitive molecular methods in PBSC collections may be distinct from cells contaminating marrow and appear to have limited utility in identifying patients with multiple myeloma and B-cell NHL who would benefit from purging strategies."
http://www.nature.com/bmt/journal/v43/n3/full/bmt2008318a.html
This has been studied because the few patients that do syngeneic (exact twin) transplants do better than patients that do autos. Those patients have clean grafts. The most famous example of a syngeneic transplant is Kathy Giusti, head of the Multiple Myeloma Research Foundation. She was cured of myeloma via a transplant from her twin sister. Patients that do syngeneic transplants typically have no problem with GVHD since their cells are an exact match. You may hear patients that do allogeneic transplants say that they have an exact match (6 out of 6 or 10 out of 10) , but only patients with exact twins truly have an exact match.
"Two large registry analyses have compared the results of syngeneic
transplantation with Auto-SCT or Allo-SCT. Gahrton et al89 reported
on 25 syngeneic recipients reported to the EBMT and Bashay et al90
reported on 43 subjects reported to the CIBMTR. The outcomes of
syngeneic transplant recipients were superior in terms of lower incidence
of relapse/progression, PFS and, for the EMBT patients, longer
OS compared to Auto-SCT. A possible explanation for this observation
would be the presence of a syngeneic GVM (as demonstrated in
animal models, but has not been successfully reproduced in humans)
91,92 or due to absence of contaminating myeloma cells in the
donor graft. This latter explanation is not supported by purging results
of Auto-SCT.93-96"
http://myeloma.org/pdfs/IMWG_JCO_allo_2010.pdf
Mark
I believe the experts think that it is what the melphalan does not kill in the body as opposed to the graft being contaminated.
"Relapsed disease remains a major obstacle following autologous haematopoietic SCT (HSCT) for non-Hodgkin's lymphoma (NHL) and multiple myeloma (multiple myeloma). Studies regarding the importance of detectable tumour cells in PBSC collections have been inconclusive. Patients undergoing autologous HSCT for NHL and multiple myeloma between 2001 and 2006 were enrolled (n=158). PBSC grafts were assessed for clonal IgH CDR3 gene rearrangements using qualitative semi-nested PCR. In comparison to patients with PCR-positive PBSC grafts, patients negative for detectable disease had no improvement in overall survival (OS) or PFS for multiple myeloma (P=0.91 and 0.91) or NHL (P=0.82 and 0.85). Further, no significant difference in OS was observed between patients with PCR-positive compared with PCR-negative PBSC grafts with aggressive NHL histology (P=0.74) or indolent disease (P=0.29). Patients with contaminating tumour cells in autologous PBSCs do not have worsened OS or PFS in multiple myeloma or NHL. Tumour cells detected by sensitive molecular methods in PBSC collections may be distinct from cells contaminating marrow and appear to have limited utility in identifying patients with multiple myeloma and B-cell NHL who would benefit from purging strategies."
http://www.nature.com/bmt/journal/v43/n3/full/bmt2008318a.html
This has been studied because the few patients that do syngeneic (exact twin) transplants do better than patients that do autos. Those patients have clean grafts. The most famous example of a syngeneic transplant is Kathy Giusti, head of the Multiple Myeloma Research Foundation. She was cured of myeloma via a transplant from her twin sister. Patients that do syngeneic transplants typically have no problem with GVHD since their cells are an exact match. You may hear patients that do allogeneic transplants say that they have an exact match (6 out of 6 or 10 out of 10) , but only patients with exact twins truly have an exact match.
"Two large registry analyses have compared the results of syngeneic
transplantation with Auto-SCT or Allo-SCT. Gahrton et al89 reported
on 25 syngeneic recipients reported to the EBMT and Bashay et al90
reported on 43 subjects reported to the CIBMTR. The outcomes of
syngeneic transplant recipients were superior in terms of lower incidence
of relapse/progression, PFS and, for the EMBT patients, longer
OS compared to Auto-SCT. A possible explanation for this observation
would be the presence of a syngeneic GVM (as demonstrated in
animal models, but has not been successfully reproduced in humans)
91,92 or due to absence of contaminating myeloma cells in the
donor graft. This latter explanation is not supported by purging results
of Auto-SCT.93-96"
http://myeloma.org/pdfs/IMWG_JCO_allo_2010.pdf
Mark
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Mark
Re: "Contaminated" stem cells vs. residual disease in the bo
I would agree with Mark's' post. There were a number of trials looking at "purging" the stem cell product of myeloma cells prior to re-infusion, and the outcomes appeared no better than with unpurged stem cells (in some cases they were worse due to delayed engraftment). So while it's not definitive, it's more likely that the relapse arises from myeloma cells resistant to the high-dose melphalan.
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Dr. Adam Cohen - Name: Adam D. Cohen, M.D.
Beacon Medical Advisor
Re: "Contaminated" stem cells vs. residual disease in the bo
My husband had Auto SCT in January 2012 and didn't get a CR. I'm wondering about this question myself. So if melphalan doesn't completely wipe out multiple myeloma, I expected the new cells to recognize that these multiple myeloma cells are bad cells and should've attacked them once engrafted. It doesn't seem like it's always the case.. is it because even these new cells no longer recognize these multiple myeloma cells as bad cells?
Re: "Contaminated" stem cells vs. residual disease in the bo
I'm about to have an ASCT, and I'm new to this website. I easily figured out the acronym ASCT, but I'm at a loss with some of the other acronyms used (PBSC, CR, PCR...). Is there a glossary on this site that will educate me? It's hard to understand the forum questions and answers, and I want to learn as much as I can before I have the procedure. I was just diagnosed with Myeloma in July, am in the early stages of it, and had 3 months of chemo with Velcade and steroids. I'm in remission now and my oncologist recommends ASCT within a month or two of ending the Velcade chemo. Is there any correlation to having the ASCT while in the early stage of the disease and the length of time before relapse?
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Donna Mc
Re: "Contaminated" stem cells vs. residual disease in the bo
Hi Letsbeatthis,
It sounds like you may not understand the immune systems role in a myeloma patient. I would say that a myeloma patients immune system is their problem. The reason for doing an allo transplant is to put a properly functioning immune system in a patient.
"It doesn't seem like it's always the case.. is it because even these new cells no longer recognize these multiple myeloma cells as bad cells?"
A myeloma patients immune system has never recognized the myeloma cells as bad - if it had the patient would not have myeloma in the first place. An auto puts the patients same immune system back in - it therefore continues to be unable to recognize the myeloma cells as a threat and continues to let them live and grow. The reason the allo can cure a patient is that the donor immune system can recognize the myeloma as foreign and destroy it.
In simple terms, your immune system recognizes things as "self" and "non self". When somone has say breast cancer, most people will say that person the immune has not identified the cancer as a threat. As myeloma patients, it is worse for us:
"Multiple myeloma cancer cells thwart many of the drugs used against them by causing nearby cells to turn traitor – to switch from defending the body against disease to shielding the myeloma cells from harm – Dana-Farber Cancer Institute scientists report in the October issue of Cancer Cell."
"The researchers found that immune-system cells known as plasmacytoid dendritic cells (pDCs) essentially assume a new identity in the presence of myeloma – promoting the growth and survival of malignant myeloma cells, helping them fend off drugs, and depleting the overall strength of the immune system.""
"This is the first time that immune system cells have been found to be converted to another function," says Chauhan, who is also a principal associate in medicine at Harvard Medical School. Investigators don't yet know how the conversion occurs, but they suspect the proteins cause a different set of genes to be activated within the pDCs."
http://www.sciencedaily.com/releases/2009/10/091005123043.htm
Based on how many Doctors here in the US treat, a patient might think they have a lenalidomide or melphalan deficiency. In reality the patient seems to have an immune system that is not functioning properly. At this time the only way of correcting that appears to be an allogeneic transplant. Fortunately I have a Doctor that recognizes that and tried to correct my real problem when the solution has the best chance of working - first CR.
Mark
It sounds like you may not understand the immune systems role in a myeloma patient. I would say that a myeloma patients immune system is their problem. The reason for doing an allo transplant is to put a properly functioning immune system in a patient.
"It doesn't seem like it's always the case.. is it because even these new cells no longer recognize these multiple myeloma cells as bad cells?"
A myeloma patients immune system has never recognized the myeloma cells as bad - if it had the patient would not have myeloma in the first place. An auto puts the patients same immune system back in - it therefore continues to be unable to recognize the myeloma cells as a threat and continues to let them live and grow. The reason the allo can cure a patient is that the donor immune system can recognize the myeloma as foreign and destroy it.
In simple terms, your immune system recognizes things as "self" and "non self". When somone has say breast cancer, most people will say that person the immune has not identified the cancer as a threat. As myeloma patients, it is worse for us:
"Multiple myeloma cancer cells thwart many of the drugs used against them by causing nearby cells to turn traitor – to switch from defending the body against disease to shielding the myeloma cells from harm – Dana-Farber Cancer Institute scientists report in the October issue of Cancer Cell."
"The researchers found that immune-system cells known as plasmacytoid dendritic cells (pDCs) essentially assume a new identity in the presence of myeloma – promoting the growth and survival of malignant myeloma cells, helping them fend off drugs, and depleting the overall strength of the immune system.""
"This is the first time that immune system cells have been found to be converted to another function," says Chauhan, who is also a principal associate in medicine at Harvard Medical School. Investigators don't yet know how the conversion occurs, but they suspect the proteins cause a different set of genes to be activated within the pDCs."
http://www.sciencedaily.com/releases/2009/10/091005123043.htm
Based on how many Doctors here in the US treat, a patient might think they have a lenalidomide or melphalan deficiency. In reality the patient seems to have an immune system that is not functioning properly. At this time the only way of correcting that appears to be an allogeneic transplant. Fortunately I have a Doctor that recognizes that and tried to correct my real problem when the solution has the best chance of working - first CR.
Mark
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Mark
6 posts
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