Can anyone who has had an allo transplant, or been involved with allo transplants for multiple myeloma patients, describe more about what they've been told or know about the option of getting a donor lymphocyte infusion (DLI) after an allo transplant.
(I think this treatment also is sometimes called a "donor leukocyte infusions".)
As I understand it, DLI is an add-on therapy for patients who have had an allo transplant.
I believe it started mainly as salvage therapy for allo patients who do not respond well to their allo transplant. But I think there are trials looking at it as a planned part of the allo transplant process.
The treatment involves getting white blood cells from the original stem cell donor and then infusing them into the myeloma patient. This is done at some point after the allo transplant has been completed.
It's not clear to me from what I've heard so far if the infusion is a single infusion, or if there are multiple infusions.
Is DLI a common procedure for myeloma patients who have undergone allo stem cell transplants? What have people who have had an allo, or considered getting an allo, been told about the procedure by their physicians?
From what I have read so far about it, it seems like a very promising approach. I found, for example, this abstract that described some promising results from a German group that is doing a lot of work focused on allo transplants:
http://www.exphem.org/article/S0301-472X%2809%2900116-7/abstract
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Re: Donor Lymphocyte Infusions - DLI - For Multiple Myeloma
Terry,
I hope you are doing well today. I did an Allo as part of upfront therapy in May - so far, so good. In Molecular Remission, no problems with Chronic GVHD yet. I am almost off my Immunosuppression, so this is the time CGVHD can develop. I have not needed any DLI's yet, but it is something I am familiar with.
I also want to point out the great work Dr. Nicolaus Kroger does at his facility. When doing my research after diagnosis, I Googled "Kroger Allogeneic Myeloma" a lot of times. Here is a great presentation Dr. Kroger gave in 2007 on using DLI's post Allo transplant. It seems that his facility is way more advanced than any here in the US - though I have been very satisfied with my Doctor and would not trade her for any multiple myeloma Doctor out there. He suggests using low dose DLI's as Maintenance if the patient has not achieved a Molecular Remission.
http://myeloma.org/ArticlePage.action?articleId=2150
So non-medical people like me can understand it, the DLI contains TCells that matured in the Donor's body. When you get the Allo, you get TCells in your Graft that matured in the Donor's body (unless you get a TCell depleted Graft, which Sloan Kettering in NY is having success with Relapsed patients - they follow up with planned DLI's). The TCells that matured in the Donor's body cause Acute GVHD because they will likely recognize the Recipient as Foreign. That is the main reason Allo patients get a Molecular Remission more often than those in the non-Allo setting. Those Tcells kill the Myeloma cells while they are active in the Recipient. DLI's can cause Acute GVHD after they are adminstered. The TCells from DLI's are more active against the Myeloma than the Tcells that have matured in the Recipients body.
I hope that explains it fairly well. Also, here is the link to how the TCell depleted Allo with planned DLI's is going at Sloan in NYC.
http://ash.confex.com/ash/2011/webprogram/Paper42075.html
Here is the link to some videos by a patient that did the TCell depleted Allo at Sloan in NY. He should be posting a video soon to discuss the DLI's. I hope this helps.
http://www.youtube.com/carpyeditor
Mark
I hope you are doing well today. I did an Allo as part of upfront therapy in May - so far, so good. In Molecular Remission, no problems with Chronic GVHD yet. I am almost off my Immunosuppression, so this is the time CGVHD can develop. I have not needed any DLI's yet, but it is something I am familiar with.
I also want to point out the great work Dr. Nicolaus Kroger does at his facility. When doing my research after diagnosis, I Googled "Kroger Allogeneic Myeloma" a lot of times. Here is a great presentation Dr. Kroger gave in 2007 on using DLI's post Allo transplant. It seems that his facility is way more advanced than any here in the US - though I have been very satisfied with my Doctor and would not trade her for any multiple myeloma Doctor out there. He suggests using low dose DLI's as Maintenance if the patient has not achieved a Molecular Remission.
http://myeloma.org/ArticlePage.action?articleId=2150
So non-medical people like me can understand it, the DLI contains TCells that matured in the Donor's body. When you get the Allo, you get TCells in your Graft that matured in the Donor's body (unless you get a TCell depleted Graft, which Sloan Kettering in NY is having success with Relapsed patients - they follow up with planned DLI's). The TCells that matured in the Donor's body cause Acute GVHD because they will likely recognize the Recipient as Foreign. That is the main reason Allo patients get a Molecular Remission more often than those in the non-Allo setting. Those Tcells kill the Myeloma cells while they are active in the Recipient. DLI's can cause Acute GVHD after they are adminstered. The TCells from DLI's are more active against the Myeloma than the Tcells that have matured in the Recipients body.
I hope that explains it fairly well. Also, here is the link to how the TCell depleted Allo with planned DLI's is going at Sloan in NYC.
http://ash.confex.com/ash/2011/webprogram/Paper42075.html
Here is the link to some videos by a patient that did the TCell depleted Allo at Sloan in NY. He should be posting a video soon to discuss the DLI's. I hope this helps.
http://www.youtube.com/carpyeditor
Mark
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Mark
Re: Donor Lymphocyte Infusions - DLI - For Multiple Myeloma
Terry,
Something that I found interesting is this. Using Conditioning prior to Allo similar to the one Dr. Kroger used for the patients that got the great outcomes that he will be presenting at ASH this year, the TRM is low for those that did the Allo as upfront therapy and while they were responsive to Chemo.
Here is a link to a study done published in 2004. Of course, Dr. Kroger was part of this study as well.
http://www.bbmt.org/article/S1083-8791(04)00272-1/fulltext
Note the last line of the paragraph related to Treatment Related Mortality:
"In a subgroup of patients with chemosensitivity and no relapse to prior high-dose chemotherapy who underwent transplantation with PBSCs (n = 46), the cumulative risk of nonrelapse mortality at 1 year was only 6% (95% CI, 1%–22%) for related (n = 34) and 8% (95% CI, 1%–54%) for unrelated (n = 12) donors."
Note that a study of Total Therapy II with and without thalidomide during that same time period also had TRM of 8%.
"In both groups, the treatments killed 8 percent of patients each year."
http://abclocal.go.com/kabc/story?section=news/health&id=3974740
Interesting that we hear that Allos are so much more dangerous than Drugs/Autos. Allos are much more dangerous if they are done in a Relapse setting. Of course, if more patients did Allos, they would not sell as much of our "Healthy Myeloma Vitamin".
Mark
Something that I found interesting is this. Using Conditioning prior to Allo similar to the one Dr. Kroger used for the patients that got the great outcomes that he will be presenting at ASH this year, the TRM is low for those that did the Allo as upfront therapy and while they were responsive to Chemo.
Here is a link to a study done published in 2004. Of course, Dr. Kroger was part of this study as well.
http://www.bbmt.org/article/S1083-8791(04)00272-1/fulltext
Note the last line of the paragraph related to Treatment Related Mortality:
"In a subgroup of patients with chemosensitivity and no relapse to prior high-dose chemotherapy who underwent transplantation with PBSCs (n = 46), the cumulative risk of nonrelapse mortality at 1 year was only 6% (95% CI, 1%–22%) for related (n = 34) and 8% (95% CI, 1%–54%) for unrelated (n = 12) donors."
Note that a study of Total Therapy II with and without thalidomide during that same time period also had TRM of 8%.
"In both groups, the treatments killed 8 percent of patients each year."
http://abclocal.go.com/kabc/story?section=news/health&id=3974740
Interesting that we hear that Allos are so much more dangerous than Drugs/Autos. Allos are much more dangerous if they are done in a Relapse setting. Of course, if more patients did Allos, they would not sell as much of our "Healthy Myeloma Vitamin".
Mark
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Mark
Re: Donor Lymphocyte Infusions - DLI - For Multiple Myeloma
Thank you very much for all that information Mark. It was very helpful. I especially liked the first link you provided. It gives a good overview of all the way DLIs can be done after allo transplants.
Do you have a sense of how regularly DLI is done in the U.S. with allo transplant patients. Also is it mainly done for patients who have relapsed?
Do you have a sense of how regularly DLI is done in the U.S. with allo transplant patients. Also is it mainly done for patients who have relapsed?
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TerryH
Re: Donor Lymphocyte Infusions - DLI - For Multiple Myeloma
Terry,
I really have not been able to find out how often they are used here in the US. Most of the information I have found related to Allos/DLI's comes from overseas. I try not to be a "conspiracy" type of person when it comes to medical issues, but many "big name" multiple myeloma Doctors in the US are paid Consultants/Board Members of Celgene. It seems most of the research here in the US is geared toward finding ways to continually using thalidomide/Revlimid, as opposed to getting long term drug free remissions for patients. For example, when I listen to Dr. Kroger (whose only Disclosures I have ever seen with respect to Celgene are that he has recieved Research Funding), I do not hear a Doctor that sounds like he is trying to keep his patients on Celgene products long term.
I did see an older paper that refers to a small study in which Myeloma patients recieved partially depleted T Cell Allos (full conditioning) and were given pre emptive DLI's if they did not have problems with GVHD. This is from the Netherlands.
http://www.nature.com/bmt/journal/v40/n4/full/1705742a.html
Here is a paper that will be presented at ASH this year that does not include Myeloma patients, but shows how well pre-emptive DLI's work in MDS/AML. Hopefully, Myeloma patients would do as well. This study is from the UK.
http://ash.confex.com/ash/2011/webprogram/Paper41920.html
The use of Anti-Thymocyte Globulin is what is often used for partial TCell depletion. For multiple myeloma patients, ATG has shown anti-myeloma properties (you can Google if interested). I am attaching a link to a 2011 ASH presentation about ATG with regards to its use in Allogeneic transplantation. I used ATG with my Allo. Note that this data is for those that did not have fully matched donors. This was done by Doctors at Mayo - Arizona, it did not include multiple myeloma patients. The conclusion of the paper was very exciting for me:
"In vivo T-cell depletion with r-ATG abrogates severe acute and chronic GVHD, and allows use of mismatched unrelated donors for allo-SCT in adult pts with otherwise incurable hematologic malignancies. Long-term survivors are generally free of severe chronic GVHD, with good quality of life. There does not appear to be an increased incidence of disease relapse, and non-relapse mortality is low. This approach is safe, effective, and considerably expands the donor pool for adult pts who require allo-SCT. "
http://ash.confex.com/ash/2011/webprogram/Paper38494.html
IMO, the strategy of using ATG before Allo and than using DLI's for those that have not achieved Molecular remission and not having GVHD is promising, especially if used in a non-relapsed setting. It does not appear that many facilities here in the US regularly use PCR testing for Myeloma (to check for Molecular Remission), as Dr. Kroger's facility in Germany does.
Mark
I really have not been able to find out how often they are used here in the US. Most of the information I have found related to Allos/DLI's comes from overseas. I try not to be a "conspiracy" type of person when it comes to medical issues, but many "big name" multiple myeloma Doctors in the US are paid Consultants/Board Members of Celgene. It seems most of the research here in the US is geared toward finding ways to continually using thalidomide/Revlimid, as opposed to getting long term drug free remissions for patients. For example, when I listen to Dr. Kroger (whose only Disclosures I have ever seen with respect to Celgene are that he has recieved Research Funding), I do not hear a Doctor that sounds like he is trying to keep his patients on Celgene products long term.
I did see an older paper that refers to a small study in which Myeloma patients recieved partially depleted T Cell Allos (full conditioning) and were given pre emptive DLI's if they did not have problems with GVHD. This is from the Netherlands.
http://www.nature.com/bmt/journal/v40/n4/full/1705742a.html
Here is a paper that will be presented at ASH this year that does not include Myeloma patients, but shows how well pre-emptive DLI's work in MDS/AML. Hopefully, Myeloma patients would do as well. This study is from the UK.
http://ash.confex.com/ash/2011/webprogram/Paper41920.html
The use of Anti-Thymocyte Globulin is what is often used for partial TCell depletion. For multiple myeloma patients, ATG has shown anti-myeloma properties (you can Google if interested). I am attaching a link to a 2011 ASH presentation about ATG with regards to its use in Allogeneic transplantation. I used ATG with my Allo. Note that this data is for those that did not have fully matched donors. This was done by Doctors at Mayo - Arizona, it did not include multiple myeloma patients. The conclusion of the paper was very exciting for me:
"In vivo T-cell depletion with r-ATG abrogates severe acute and chronic GVHD, and allows use of mismatched unrelated donors for allo-SCT in adult pts with otherwise incurable hematologic malignancies. Long-term survivors are generally free of severe chronic GVHD, with good quality of life. There does not appear to be an increased incidence of disease relapse, and non-relapse mortality is low. This approach is safe, effective, and considerably expands the donor pool for adult pts who require allo-SCT. "
http://ash.confex.com/ash/2011/webprogram/Paper38494.html
IMO, the strategy of using ATG before Allo and than using DLI's for those that have not achieved Molecular remission and not having GVHD is promising, especially if used in a non-relapsed setting. It does not appear that many facilities here in the US regularly use PCR testing for Myeloma (to check for Molecular Remission), as Dr. Kroger's facility in Germany does.
Mark
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Mark
Re: Donor Lymphocyte Infusions - DLI - For Multiple Myeloma
Greetings from ASH in rainy San Diego Terry,
I took this definition of DLI from Wikipedia because it is as good as any other.
From Wikipedia:
Formerly, the only treatment option that offered relapsed bone marrow transplant patients hope of a cure was another bone marrow transplant. However, the risk of serious, life-threatening complications after a second BMT is great. One strategy of managing relapse, donor leukocyte infusion, can salvage some patients in relapse after alloBMT.
Donor leukocyte infusion is the infusion in which lymphocytes from the original stem cell donor are infused, after the transplant, to augment an anti-tumor immune response or ensure that the donor stem cells remain engrafted.These donated white blood cells contain cells of the immune system that can recognize and destroy cancer cells.
The goal of this therapy is to induce a remission of the patient's cancer by a process called the graft-versus-tumor effect (GVT). The donor T-cells can attack and control the growth of residual cancer cells providing the GVT effect ( as was hoped with the initial but failed allogeneic stem cell transplant) It is hoped that the donor leukocyte infusion will cause GVT and lead to a remission of the patients cancer.
Patients may require further chemotherapy, to reduce the amount of cancer cells they have prior to their donor lymphocyte infusion.
Complications of DLI include acute and chronic graft-versus-host disease and bone marrow aplasia, resulting in immunosuppression and susceptibility to opportunistic infections.
- - - - -
So.....DLI is not the primary therapy but is used in hematologic cancers like myeloma/leukemia when they relapse after an initital allotransplant.
DLI is often used in relapsed disease after allo transplant all over the world but unfortunately it does not routinely result in "rescue" for patients with aggresive disease. In addition there can be many severe side effects.
Because of the risks DLI is generally not part of a allogeneic stem cell transplant procedure unless a patient relapses. There are studies underway to look at the possiblity of using DLI to enhance the graft versus tumor effect of allogeneic stem cell transplantation.
I took this definition of DLI from Wikipedia because it is as good as any other.
From Wikipedia:
Formerly, the only treatment option that offered relapsed bone marrow transplant patients hope of a cure was another bone marrow transplant. However, the risk of serious, life-threatening complications after a second BMT is great. One strategy of managing relapse, donor leukocyte infusion, can salvage some patients in relapse after alloBMT.
Donor leukocyte infusion is the infusion in which lymphocytes from the original stem cell donor are infused, after the transplant, to augment an anti-tumor immune response or ensure that the donor stem cells remain engrafted.These donated white blood cells contain cells of the immune system that can recognize and destroy cancer cells.
The goal of this therapy is to induce a remission of the patient's cancer by a process called the graft-versus-tumor effect (GVT). The donor T-cells can attack and control the growth of residual cancer cells providing the GVT effect ( as was hoped with the initial but failed allogeneic stem cell transplant) It is hoped that the donor leukocyte infusion will cause GVT and lead to a remission of the patients cancer.
Patients may require further chemotherapy, to reduce the amount of cancer cells they have prior to their donor lymphocyte infusion.
Complications of DLI include acute and chronic graft-versus-host disease and bone marrow aplasia, resulting in immunosuppression and susceptibility to opportunistic infections.
- - - - -
So.....DLI is not the primary therapy but is used in hematologic cancers like myeloma/leukemia when they relapse after an initital allotransplant.
DLI is often used in relapsed disease after allo transplant all over the world but unfortunately it does not routinely result in "rescue" for patients with aggresive disease. In addition there can be many severe side effects.
Because of the risks DLI is generally not part of a allogeneic stem cell transplant procedure unless a patient relapses. There are studies underway to look at the possiblity of using DLI to enhance the graft versus tumor effect of allogeneic stem cell transplantation.
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Dr. Edward Libby - Name: Edward Libby, M.D.
Beacon Medical Advisor
Re: Donor Lymphocyte Infusions - DLI - For Multiple Myeloma
I had an allo transplant at DF in 1996. It was t-cell depleted. About 6 months later I had the DLI. They came from my brother who was a complete match. Since I am typing this now, it achieved it's goal. I am in complete remission.
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paulw
Re: Donor Lymphocyte Infusions - DLI - For Multiple Myeloma
PaulW,
Your post made my day. 17 years of remission - Congratulations! You have a great Doctor.
Mark
Your post made my day. 17 years of remission - Congratulations! You have a great Doctor.
Mark
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Mark
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