Manhattan Tales: Stem Cell Transplants – How Far We Have Come
Before I was diagnosed with multiple myeloma in 2010, medical science was not my field of expertise, but rather my wife’s. She is a pediatric endocrinologist and had taught me about pediatric diabetes and other metabolic disorders.
I, on the other hand, was an expert in municipal law. I also had developed an expertise in construction accidents because, for eight years, I had been working with a New York City government agency that regulated construction. I was responsible for editing many of the reports on construction accidents that affected the public, and the agency’s structural engineers patiently taught me the basic principles of construction safety.
The focus of my studies changed with my myeloma diagnosis.
After I was told that I would need a stem cell transplant, I read the various booklets and articles the medical team provided because I don’t think I had heard of a “stem cell transplant” before. I may have heard of bone marrow transplants but certainly could not distinguish between the two.
After reading all the material, I only got a rudimentary idea of the procedure. I knew that there were four basic steps:
First, before the transplant, some of my own stem cells would be “harvested” over the course of a couple of days by putting a needle in my arm, collecting my blood and spinning it through a centrifuge machine. The stem cells would be separated from the other blood components, and the remainder of my blood would be returned to me.
Second, my stem cells would then be frozen until the transplant.
Third, when I was ready for the transplant, I would be given a dose of high-dose chemotherapy that would kill my bone marrow.
Finally, after the bone marrow was killed, my harvested stem cells would be retrieved from the deep freeze and would be given back to me intravenously. My blood stream would transport the stem cells to my bones, and they would re-seed my bone marrow. My bone marrow, over the course of a few weeks, would grow back and start producing healthy blood cells. The myeloma would eventually return, but meanwhile any concentrations of it that had existed in my blood or bone marrow would be sharply reduced if not eliminated.
Over the last few months, I decided to try to learn more about the history of stem cell transplants.
I read many articles on the web and found the history so fascinating that I decided to try and make a list of some of the major achievements. I could then perhaps understand more of the procedure that I had gone through a couple of months ago. Perhaps I could even explain the process in a bit more detail to my friends who asked.
After reading these articles and accounts of the development of these procedures, I am simply in awe at the brilliance and persistence of the scientists and researchers involved.
I am also in total awe at the bravery of the doctors and the patients who were willing to try these new procedures. While tens if not hundreds of thousands of stem cell transplants have now been performed, it must have taken incredible courage to have been involved when the procedure was novel.
I thought I would share my understanding of some of the main scientific accomplishments that led to this now widely used procedure.
As I already pointed out, every one of the steps was an extraordinary accomplishment.
Blood stem cell transplants were clinically introduced just 26 years ago, in 1986. They now vastly outnumber bone marrow transplants, where some of a patient’s (or a donor’s) bone marrow is actually removed from the bones and then transfused into the patient’s bloodstream.
Stem cell transplants account for virtually all autologous transplants (where the patient’s own cells are used) and 75 percent of allogeneic transplants (where a donor’s cells are transplanted). They are far less arduous than bone marrow transplants, which require anesthesia for both the donor and the patient.
Although scientific progress can be divided any number of ways, the articles I read came up with seven or eight critical steps in the development of the stem cell transplant procedure. In more or less chronological order here is my list:
- In the 1950’s, scientists discovered that certain cells in the blood were capable of generating other components of blood – red cells, white cells, plasma and platelets.
- In the mid-1960’s, an engineer at IBM, whose son was ill with leukemia, oberved the difficulty in collecting white blood cells. Working with researchers at the National Cancer Institute, he and his colleagues at IBM developed a machine that could separate these different blood components from one another on a continuous flow basis. The essential process behind the machine is a centrifuge. It spins the blood, which then separates into layers depending on the component’s’ specific gravity. The collection of the different blood components by the centrifuge is called “apheresis.”
- At about the same time in the 1960’s, dogs whose bone marrow had been destroyed by radiation were successfully treated with transplants. When the dogs were transfused with cells from their own blood or with cells from other dogs, their bone marrow grew back and their blood was reconstituted. The term “blood stem cell” was coined, as these blood cells can reproduce all types of blood cells, similar to the way that embryonic stem cells can develop into any type of human cell.
- In the 1970’s, a successful stem cell transplant was performed in a human. Nevertheless, the process did not quickly come into widespread use as the procedure did not prove reliable. The procedure may not have been consistently successful because insufficient numbers of stem cells from the donors were collected and because the stem cells given to patients did not reconstitute blood cells quickly enough.
- In the late 1970’s, a technique called “cryopreservation” was developed that allows stem cells to be collected and stored over an extended period of time. Cryopreservation involves cooling the stem cells to a sub-zero temperature and storing them in liquid nitrogen. By the mid 1980’s, several successful stem cell transplants were performed by collecting stem cells through multiple apheresis procedures and preserving them at low temperatures till needed.
- In the late 1980’s, the procedure was further improved by the use of growth factors, which are agents injected into the blood to stimulate the production of stem cells. Results from two clinical trials showed that growth factors increased the production of stem cells 100 fold before the harvest and thus increased the yield of stem cell collection during apheresis. In addition, growth factors can be given to patients soon after transplant to increase the production of blood cells.
- Until the 1990’s, allogeneic (donor) stem cell transplants were not performed because of concerns that the donor stem cells identify the recipient’s cells as foreign and attack them. This problem, called “graft-versus-host disease,” was overcome by the development of a technique called HLA typing that allows doctors to match recipients with appropriate donors. Allogeneic stem cell transplants are now widely used in various blood cancers and other diseases.
- Finally, antibiotics and anti-fungal, anti-shingles, and anti-nausea medicines came into use that significantly eased the dangers and discomfort of the transplant process. Destruction of the bone marrow during chemotherapy destroys the immune system and makes patients highly susceptible to infections. The anti-infectives substantially lowered the infection risk of stem cell transplant patients.
A huge amount of research and clinical trials is going on now in the various blood cancers. Similar to what has happened over the past 50 years, the research will assuredly make a huge difference to the next generation of cancer patients – and, hopefully, to us, the current generation.
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Hi Stephen, I also think that we are lucky to be in the '2010s' as far as treatments for Myeloma go. The stem cell transplants, and allogenic transplants are much safer now than they used to be, and the new chemotherapy drugs hold out so much promise too. We do stand on the shoulders of all the patients, researchers and medical people who have gone before us. Stay well, and thanks for the column, on the history of transplants.
Wonderful summary. I agree those MM patients are heroes for leading the charge for all of us. The researchers are brilliant and we all benefit from the research. I am grateful everyday and weekly when I receive the velcade treatments.
All MM patients who opt for transplants -- even today - must be commended.
Autologous transplants still don't cure, are overused, have a host of horrible side effects, and often cause long-term destruction of the immune system due to the otherwise lethal dose of mustard gas that precedes them.
And bloody hell: then there is self-destruction from allogenic transplants owing to graft versus host disease. This largely NOT been overcome -- even with HLA-matched donors. You may not die from the transplant, but you may well succumb to the subsequent attack against your body.
Thanks for the great overview of the progress made in transplantation. I always like to mention the real heroes of allo transplants - the Donors. I used an unrelated Donor for my transplant. They donate their stem cells/marrow to a total stranger to try and cure them of cancer. They are great people. Since everyone reading this is affected in some way by blood cancer, I would hope that they would ask any healthy person they know under the age of 60 to go to the website of the Be the Match Registry - http://www.marrow.org - to check about potentially being a Donor.
Wondering obviously knows little about allo transplants or myeloma in general. Patients with myeloma have poorly functioning immune systems to begin with. Healthy immune systems do not produce cancerous plasma cells, allow cancerous plasma cells to grow, and help protect cancerous myeloma cells against drug therapies. A myeloma patients immune system has plenty of abnormalities long before they recieve therapy.
"Immune Abnormalities in MM Patients
The number and function of T cells subsets are aberrant in patients with MM [5, 6]. The CD4 : CD8 ratio is inverted and the helper T-cell type 1 to type 2 (Th1 : Th2) ratio among CD4 cells is abnormal [7]. In addition, the levels of expression of CD28 costimulatory molecules required for T cell activation are downregulated in T cells derived from MM patients [8]. The elevated levels of transforming growth factor (TGF)-β, in addition to the impaired accessory signals from Th cells, contribute to the presence of dysfunctional B cells [9]. Defective natural killer cells (NK) have also been noted in MM patients [10]. Circulating dendritic cells (DCs) from MM patients were shown to be dysfunctional, failing to upregulate costimulatory molecules required for DCs activation, which led to reduced phagocytic activity and antigen presentation [11]."
http://www.hindawi.com/journals/bmr/2011/269519/
The stem cell transplant certainly is not a cure, but it sure is a lot easier on the patient and the donor than the bone marrow transplant that it has generally replaced. Lord knows how long it will keep my myeloma at bay, but most days I am able to remember the mantra "every day is a gift."
A great powerpoint describing George Judson's development of the apherisis machine is on the web at ctandi.org/pdfs/IBM%20Blood%20Machines%20.pps. And a great article also on the web going over the history of stem cell transplants is "25 Years of Peripheral Blood Stem Cell Transplantation" by Martin Korbling and Emil Freireich, from the journal “Blood”, prepublished on the web on April 1, 2011
Great article! I had been wondering about "stem cells" vs. "blood stem cells." The other information was fascinating too. I just looked over the history of the development of the apherisis machine -- it is a technical marvel.
I was diagnosed stage 3 MM June 2011. I also had the autologus transplant & was told 3 days ago by the stem cell oncologist that I was in remission, BUT I should still do the allogenic transplant.
My research into allogenic t/plants is that it is still in a "gray" area for Myeloma patients. The oncologist who originally diagnosed me did not recommend doing it. ""50% chance of GVHD is too high."" As "Wondering" said I must agree. The side effect alone from your own stem cell transplant is devastating on the body ...why would I even think about doing the allogenic t/plant which has a 50% chance of killing me and be more devastating to the body if I survive it.
I read on the MM website there is no cure, but my 2nd oncologist kind of implied the allogenic would cure it !!!!!! I am not sure if I misunderstood him.
I have been trying to find fellow MM patients that have had the allogenic transplant but have not succeeded in finding any.
Lastly, to all the 6 commenters above me, I wish you well and continue to fight the battle.... When I was diagnosed, I did not cry or whine "why me". This the hand I was dealt so I played the cards, so after 1 year the score is 1 to 1. I may not win the war, but I DID win the first battle.
Thank you Stephen for all your info.
Gloria,
I did an allo in Spring 2011 as soon as I got into my first CR. I am doing great - I have no problem with GVHD and I have a perfectly functioning Donor immune system. I jog, lift weights, and live a perfectly normal life. The transplant has had no "devastating" side effects that I have noticed. The NIH did a study that concluded with this about bllod cancer patients 5 years after T Cell depleted allos:
"Most survivors beyond 5 years had an excellent performance status with no difference in physical and mental health and higher HRQL scores (P = .02) compared with population norms. Although physical and psychologic symptom distress was low, those with higher symptom distress experienced inferior HRQL. These results show that 5 or more years after T cell-depleted HSCT for hematologic malignancy most individuals survive disease free with an excellent performance status, preserved physical and psychological health, and excellent HRQL."
http://www.ncbi.nlm.nih.gov/pubmed/20302959
That does not sound like people that have their immune systems attacking their bodies to me. It is a fact that patients taking drugs like Revlimid, carfilzomib, Velcade and DEX do not have Health Related Quality of Life on par or better than population norms. Long cycles of those drugs have bad side effects on patients. That is the choice - early allo or lots of drugs like Revlimid, Velcade, carfilzomib, etc.
Where in the world did you get the idea that an allo had a 50% chance of killing you when done early in disease course? This study shows 6 or 8% for patients doing them early in disease course.
"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."
http://www.bbmt.org/article/S1083-8791(04)00272-1/fulltext
Mark
Hello Gloria,
An allo transplant is not commonly done with newly diagnosed myeloma patients. In fact, I think there are guidelines recommending against it unless it's done as part of a clinical trial. As you mentioned, there is a higher risk of death as a result of an allo compared to an auto transplant. I agree with Mark, however, that the risk is not anywhere near 50 percent, at least not for someone in your situation.
I think you should do more searching here for articles and forum postings that discuss allo transplants. You'll learn about the risks, but you'll also learn that allo transplants are considered the only treatment option that can truly cure a myeloma patient. Look, in particular, for comments or forum discussions Mark has taken part in. He provides a lot of useful information.
I think you also need to learn more from your oncologist about why he/she wants to do an allo with you at this point. I suspect the reason may be that your oncologist is concerned that, even though you've responded to your latest treatment, you may be at high risk of relapsing again. Doing an allo transplant now, before you've relapsed, and while you're still reasonably healthy, may be the best way of prolonging your remission and possibly even permanently getting rid of your myeloma.
What was your treatment before your auto stem cell transplant? Also, did your oncologist ever tell you what your "risk" classification was, like "low risk" or "high risk"? These are issues the oncologist is probably considering.
Hi Gloria,
I'm only chiming in here to let you know of another "auto-allo" patient who gratefully took the risk, but who was never given such a dire prognosis of 50%! I was told that there was a 15% risk of dying from such a procedure, but that due to my youth (45 years) and other factors (no other issues, really, other than the fact that my MM knew how to work around the RVD after a few months, but no other high-risk factors) my doctor did not believe the mortality rate applied to me. And my donor, my brother, was only a half-match, and so I had a mini haplo allogeneic transplant just a few months after the auto.
I had a VGPR after the auto, and showed every indication of eventually reaching a CR based on the trends, but my doctor felt strongly that I should proceed to the allo and initiate a "pre-emptive strike" (her words). She used "war" vocabulary, as you referenced, and as a history buff, that really struck a chord with me. She assured me that there was nothing wrong with waiting until the "enemy" struck again, but that in her opinion, I did not have the right weapons (i.e., immune system) to fight off such an attack. She believed that the best weapon in my arsenal would be a new immune system, based on how quickly my disease rebounded from the best drugs she could possibly throw at it.
And so, with very little research and a leap of faith, I decided to go for it. I will tell you honestly that the past year, almost a full year since my allo, has been the most normal, wonderful year since my diagnosis in December, 2009. I have been off all chemo (after 18 months of constant, intense therapy), which itself is amazing, and I don't think anything but firsthand experience could have prepared me for that immense difference in QOL. The minor GVHD that I have experienced is nothing to complain about, and in fact is a comforting factor (teary eyes, slightly sensitive mouth) because it reassures me that I have an active immune system.
There may be horror stories out there, somewhere, and those people probably aren't blogging about their trials, but thanks to Mark, I have been doing more research and have met others whose lives have been changed by allos. I can say with full confidence that my doctor, who is generally quite conservative, would not have suggested I undergo an auto-allo tandem unless she was sure it was the best option for me. In fact, she has since told me that I am the first patient (with a half-match donor) for whom she has suggested such therapy. My constant prayer is that she will think outside the box for me!
So please know that we "allos" are out there, and I think you are wise and brave to look into all this in advance! Best of luck in your decision! We live in a time of great hope for multiple myeloma!
Blessings, Dana
I completely agree with Mark that chronic use of drugs like revlimid and velcade, and most likely carfilizomib and pomalidomide, is a bad, bad thing.
So the question is how to avoid such long-term use. Foregoing chemical maintenance with such drugs after acute treatment is one option -- although people seem gun-shy of such an approach. But in cases where one does not have an aggressive and proliferative disease -- and treatment kncks it back to a VGPR or better, I think it is worth considering. I know I am. Right now my M-spike is below 1 after two cycles of Rev plus dex, I am experiencing no side significant effects, my Hb has increased from 8 to 12, and my metabolic profile and other blood counts are otherwise close to normal. So I am pleased but do not want to get into extended treatement....
In this regard, I can't help wondering if total therapy by Barlogie simply accepts long-term toxicity, if not secondary cancers, as worth it -- if you can potentially achieve a cure. But blogs such as that of Nick -- with indicators of aberrant immune function seen with vasculitis and potential concerns of MDS -- make me question the sacrifice and long-term side efffects of this therapy.
Ineed, I have yet to see a happy list of what one might expect to be thousands of UAMS patients have undergone such therapy expounding their cure and high quality of life. Instead I suspect many patients are riddled with neuropathy and other devastating consequences in their over-aggressive quest for a cure....and let's not keep in mind that with the right low-risk factors, the median life span of a MM patient is more than 11 years anyways - so what is Barlogie REALLY selling? We already know his treatment does NOT work for high-risk patients anyways.
No question then that allogenic transplants, if warranted and timely, can achive a potential cure with minimal long-term side effects. Just not sure whether Mark is the exception rather than the rule of great success with this treatment. But to the extent that I may consider a transplant down the road, it will likely be allogenic rather than autologous.
But in in interim, I am also looking into vaccines as well.
Great discussion!
Cheryl G - Thanks for the compliment. I agree with everything you said. I would just say that the guidelines discouraging early use of allos and saying they should only be done as part of a clinical trial represents the majority OPINION. That opinion is partly influenced by the fact that the average patient is diagnosed at approximately 70 years old and allos are not an appropriate therapy for that age group. My allo was not done as part of a clinical trial. Unfortunately the Doctors that discourage early use of allo transplants have no alternative therapy that can potentially cure patients.
My Doctor and Gloria's are definitely in a small minority that think trying to cure patients with allos early is worth the risk. IMO it should be up to the individual patient to decide along with an experienced allo Doctor if the procedure is right for them. Unfortunately many of the "big name" myeloma Doctors are not experienced allo Doctors. I would also point out that allos have been done on myeloma patients since the 1980’s. It actually has one of the longest track records of all myeloma therapies and it is the therapy that has produced the largest number of long term survivors. I do not understand how Doctors that recommend long term use of newer drugs like Revlimid and Velcade could say that allos should be considered “experimental therapy”.
Dan D - I agree with you, especially with respect to long term Revlimid use . I posted an article about secondary cancers in the forum. For me, the big take away from the article is that the Doctors do not really know what all Revlimid is doing to patients. It is surprising to me Doctors would recommend taking a drug continuosly that they do not know what the long term side effects are and taking it as maintenance shows no Overall Survival benefit. Even the recent study that the Doctors claim shows an OS benefit turns into a slight advantage for no maintenance on longer term followup.
"A truly satisfactory explanation would require a better understanding of how lenalidomide works in patients with hematologic malignancies, let alone myeloma."
http://www.hindawi.com/journals/ah/2012/801495/
It is difficult to know if I am the rule or the exception for a couple of reasons. Statistics with allos are often mixed between patients that do them when they have their best chance of success (in first CR, like mine) and when done in a relapsed setting when the chance of success is not as high and the chance for significant side effects is greater. The statistics are much different depending on which setting they are used. The other problem is with how Chronic GVHD is reported. Chronic GVHD is only reported as "Extensive" or "Limited". I think patients assume that when it is reported as Chronic that it is an ongoing problem. That is not necessarily the case. If it occurs more than 90 days after the transplant it is referred to as Chronic. To use me as an example, the first month I got off all my immunosuppression (about 6.5 months after transplant), I had a mild skin rash and sore gums for about 2 weeks. Both symptoms went away without any treatment and never returned. Therefore I did have limited chronic GVHD. I would hate to think younger patients are foregoing the only chance at a cure because of a misunderstanding of what the side effects of allos are. I would gladly take those side effects for two weeks as opposed to the side effects long term Revlimid, DEX, Velcade, carfilzomib, etc cause.
This discussion raise some important points about upfront allos for the right population of patients.
And Mark is certainly educating me as to the potential misunderstanding regarding chronic GVHD. Indeed, as we know, a bit of GVDH can be a good thing, because it indicates that the donor immune system is most likely mopping up "foreign" residual cancer cells.
Make me wonder why UAMS does not advocate such transplants for younger, low-risk patients? It makes sense to me that they should...
Of course, Celgene is a big fan of maintenance.
You're welcome, Mark. I will add, though, that as much as I think you provide a ton of useful information related to allo transplants, I don't think it's quite fair to say that it's just "opinion" that guides a lot of what myeloma specialists say in regard to allo transplantation.
There was a major clinical trial done that looked at the benefit of allo transplantation versus auto transplantation, and it did not find any benefit. It's summarized in this article:
http://www.myelomabeacon.com/news/2010/12/06/donor-stem-cell-transplants-come-up-short-as-second-transplant-option-in-multiple-myeloma-patients-ash-2010/
and also in this abstract:
https://ash.confex.com/ash/2010/webprogram/Paper30659.html
True, the study compared a sequence of two auto transplants to a sequence of one auto and one allo transplant, but the result is still important. And the result is that the patients who got the auto-allo sequence had lower progression free survival and overall survival rates than the auto-auto patients.
Notable is the fact that the auto-allo patients had a treatment-related mortality rate of 11 percent versus 4 percent for the auto-auto patients.
Also, if you look at the protocol for the study, which you can view here,
http://clinicaltrials.gov/ct2/show/NCT00075829
you'll see that the study included only patients that were under 70 years of age. So these were not very old patients.
I realize one can make arguments about whether the allo part of the trial reflected all that we now know about the best way to do allo transplantation.
But this head-to-head trial really has to be mentioned in any discussion of the pros and cons of allo transplantation.
Cheryl G,
Believe it or not, I pretty much agree with what you said about the study and my doctor would definitely agree about "mini" transplants. She does not think "mini" transplants work very well. I did a myeloablative allo. The comment she and I would disagree with is:
"I realize one can make arguments about whether the allo part of the trial reflected all that we now know about the best way to do allo transplantation."
I brought up the subject of a "mini" to her and she said something like "statistically those things have the same mediocre results as tandem autos with maintenance". Unfortunately 2GY of radiation does not seem like enough conditioning to cure a high percentage of patients. A recent German study addressed this issue:
"The treatment of multiple myeloma is still unsatisfactory. Although in recent years survival improvement was seen, disease progression just seems to be deferred. Even after high dose chemotherapy and autologous stem cell transplantation (ASCT), most patients relapse. "
Treatment options fo those patients are, despite promising newer drug, still limited.
In contrast, allogeneic human stem cell transplantation (HSCT) bears the potential of definite cure, however, being hampered by inacceptable high Treatment Related Mortality (TRM) rates. Reduced intensity conditioning (RIC) regimens lead to a drop in TRM, but this benefit is offset by higher relapse rates. Hence, in three recently published prospective studies no consistent superiority in Overall Survival (OS)/Progression Free Survival (PFS) was seen for RIC HSCT when compared to ASCT."
"Risk factors being associated with diminished PFS and OS (given data) were >1 prior ASCT (OS:HR=2,80, p=0,00;PFS:HR=2,76; p=0,00), allo-HSCT more than 10 months after last ASCT (OS:HR=2,09, p=0,012;PFS:HR=2,47, p=0,001), no partial remission (PR) at time of HSCT (OS:HR=2,41, p=0,002;PFS:HR=2,31, p=0,002), application of a "reduced intensity conditioning" (OS:HR=2,11, p=0,009;PFS:HR=1,93, p=0,015) and a lower CD 34/MNC count (OS:HR=1,89, p=0,047;PFS:HR=1,82, p=0,040) in univariate analysis.
In multivariate analysis >1 prior ASCT (OS:HR=2,81, p=0,001;PFS:HR=2,89, p=0,000) and "RIC" (OS:HR=2,00, p=0,022;PFS:HR=2,09, p= 0,010) could be confirmed as independent risk factors. Patients reaching at least a PR prior to HSCT and lacking the latter two risk factor reached an OS of 60% and PFS of 50% with a follow-up till 17.5 years."
"Summarizing the results, we established >1 prior ASCT as an independent risk factor for subsequent HSCT, contradictory to the use of double ASCT as standard therapy, especially in younger patients. Furthermore we saw moderate TRM rates after "myeloablative" HSCT, resulting in a significant better outcome compared to the RIC regimen. This observations raise the question if early and myelablative HSCT might be the key to cure multiple myeloma."
https://www.eventure-online.com/eventure/publicAbstractView.do?id=190223&congressId=5650
Although my doctor does not like to perform "mini" allos I still hold out hope for the "mini" allo because there are some success stories with the procedure and some studies show and advantage to auto-"mini" allo to tandem auto.
http://www.nejm.org/doi/full/10.1056/NEJMoa065464
Mark
Mark & Dan & Cheryl
Awesome discussion!
Thanks Mark for the greater specificity on GVHD. I can honestly say the idea of chronic GVHD is a big deterrent for me. As is TRM outweighing benefits of PFS/OS.
Dan, I have not ever believed in UAMS. The data and techniques promulgated there are more like the Mengele of MM to me.
I have always admired your courage Mark, and I do think allo does offer the best chance for 'cure' hopefully I can as courageous as you.
Cheryl, TRM is much higher with allo, but then auto's fail, 50% of the time and do not offer a hope for a 'cure' and as Dan and Mark mention, the patient typically is on long-term maintenance and while that is better than disease progression there are long term toxicity risks.
"This observations raise the question if early and myelablative HSCT might be the key to cure multiple myeloma.”
YES!
I often wonder if the progress with allos has been slower simply because it will remove patients from the long term market in terms of profitability. IOW's cures are not profitable.
HI ALL, I am also following this discussion with interest. It would be nice to think that 'allos' would solve most of the problems for myeloma patients relapsing, and it is great that the 'One Match' system is in place too. i could be wrong but I think that 'allos' are the only option for some blood cancer patients...leukemias for example. Those patients simply cannot do an 'auto' transplant. When I was at the hospital, I met a younger woman who had leukaemia who wanted to do a transplant, but no match had been found for her yet. That is a big problem. At least with myeloma we do have 'auto' transplants available to some of us, and yet that is not even for all myeloma patients, due to other scientific genetic considerations. I also know a person whose brother had one of those other blood cancers, and who did not survive an allo transplant. She of course was horrified when she heard I had a stem cell transplant, thinking it was an 'allo' I guess. That has of course tempered my enthusiasm for 'allo' transplants! bUT hopefully medicine improves all the time, sometimes just incrementally and sometimes by leaps and bounds, and I do hope that better long term remission rates occur in the future.
Anyone here read up on Maraviroc? It's an AIDS drug that was recently administered in a clinical trial to combat GVHD in allogeneic transplants across various blood cancers.
Hi Ronald,
I posted about Selzentry (maraviroc) on the forum a few weeks ago. Here's the link:
http://www.myelomabeacon.com/forum/selzentry-and-graft-versus-host-disease-t1176.html
Hi Mark, I do appreciate all your information on 'allo' transplants and am very happy for you that it worked well for you! Obviously there are others like you who have written in too!
This series of exchanges have been a good education to me. But for an allo to be a realistic option, besides the courage, a matching donor has to be found, which could be an unsurmountable obstacle by itself. Then there is the issue of insurance coverage, because it is most certainly viewed as "experimental" in that corner of the world.
Hi Ronald,
Just as a quick follow up to my previous comment, there's a new study out that shows that a short round of treatment with Velcade also may reduce GVHD and improve outcomes after mini allo transplants with mismatched donors. I just posted about it in the forum; here's the link:
http://www.myelomabeacon.com/forum/velcade-after-mini-allo-transplants-t1235.html
Thanks, Mark, for clarifying that the study I mentioned involved mini allos. I hadn't picked up on that, and it's certainly an important point. However, its importance cuts both ways.
It means that the allos used in the trial probably were not as effective as would have been observed with "full" allos. But it also means the treatment-related mortality seen in the trial was probably lower than would have been seen with full allos.
I'm not sure why you would object to my statement "I realize one can make arguments about whether the allo part of the trial reflected all that we now know about the best way to do allo transplantation."
I actually was admitting that the approach to allo transplantation used in the trial may not have been the most advanced and up-to-date. I made this statement thinking it might prompt some discussion as to what the weak points were of the allo part of the trial. And, in some ways, that's exactly what you did!
I do think that one reason there is not as much research into allo transplantation as there is, for example, into new drug treatments is that no single company is likely to benefit from advances in allo transplantation. That is why one would hope that organizations such as the National Cancer Institute or the MMRF would fund such research. (Although it's probably too much to expect the MMRF to support such research, given how dependent it is on drug company money.)
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