Day Of Rest Between Melphalan And Stem Cell Infusion May Not Be Necessary For Myeloma Patients
Multiple myeloma patients receiving an infusion of their own stem cells either one day or two days after undergoing treatment with high-dose melphalan demonstrate similar clinical outcomes, according to a recent U.S. study.
The study investigators conclude that a day of rest between treatment with melphalan and stem cell infusion appears not to be necessary. Based on their findings, they recommend that melphalan administration the day before stem cell infusion should be considered as standard of care.
According to Dr. Giampaolo Talamo of the Penn State Hershey Cancer Institute in Hershey, Pennsylvania, and lead investigator of the study, the two most important benefits of giving melphalan as a single dose on the day prior to transplantation are decreased costs and simplification of the treatment process.
“It simplifies the process for patients, doctors, and nurses. Less material like intravenous lines and bags, and less time and supervision spent for the administration of chemotherapy,” said Dr. Talamo. “Besides cutting the cost of material and personnel, it cuts the cost of the transplant because it requires a day less in the hospital.”
An autologous stem cell transplant is a procedure in which stem cells are harvested from a patient prior to high-dose chemotherapy and later re-infused into the patient’s body to replace the cells that were destroyed by chemotherapy. This procedure is a standard course of treatment for multiple myeloma patients aged 65 years and under.
Melphalan (Alkeran) is the chemotherapeutic agent generally used with stem cell transplants for myeloma patients. According to the study investigators, many treatment centers typically wait at least 24 hours between melphalan administration and stem cell infusion, believing a “day of rest” in between may be necessary to avoid any possible negative effects of chemotherapy on the re-infused stem cells.
The study investigators point out, however, that the “schedules of administration are based more often on empiric policies than scientific rationale or data.”
This lack of data led researchers from the Penn State Hershey Cancer Institute and the University of Utah to evaluate whether the timing between treatment with melphalan and an autologous stem cell transplant would have an impact on clinical outcomes.
The study investigators retrospectively analyzed data from 138 myeloma patients treated at the Penn State Hershey Cancer Institute who received high-dose melphalan followed by an autologous stem cell transplant between 2007 and 2010. The median age of the patients was 59 years.
From 2007 to 2008, patients received high-dose melphalan two days prior to stem cell infusion. The policy was then changed, and patients began to receive stem cell infusions the day after receiving melphalan, sometimes as little as eight hours later.
Thirty-four percent of patients were treated with melphalan two days prior to transplantation, while 66 percent received melphalan one day before the transplant. The median dose of melphalan administered (190 mg/m2 two days prior to transplant or 182 mg/m2 one day prior to transplant) and the median number of stem cells infused (4.7 million cells/kg two days after melphalan or 5.1 million cells/kg one day after melphalan) were similar for both groups.
Likewise, time until stem cell engraftment and recovery of blood cell counts were similar for the two groups.
Responses were evaluated six to eight weeks following transplantation. The overall response rates for patients who received melphalan two days prior to transplantation and one day prior to transplantation were similar (96 percent versus 95 percent, respectively).
The one-year progression-free survival rates (90 percent versus 87 percent) and one-year overall survival rates (96 percent versus 99 percent) were also similar.
For more information, please see the study in the European Journal of Haematology (abstract).
Related Articles:
- Stem Cell Transplantation May Be Underutilized In Multiple Myeloma Patients In Their 80s
- Selective Digestive Decontamination May Reduce Risk of Infection In Myeloma Patients Undergoing Autologous Stem Cell Transplants
- Revlimid, Velcade, and Dexamethasone, Followed By Stem Cell Transplantation, Yields Deep Responses And Considerable Overall Survival In Newly Diagnosed Multiple Myeloma
- Number And Type Of Stem Cell Transplants Carried Out Each Year For Multiple Myeloma Vary Markedly Across U.S. Cancer Centers
- Nelfinavir Shows Only Limited Success In Overcoming Revlimid Resistance In Multiple Myeloma Patients
UGH!!
...so what does this tell us EXACTLY about lethal doses of chemo?
Hmmmmm......the outcome of lethal doses is independent of when they do the stem cell rescue...now why does that make sense...o yeah that's right...early or 2 day delayed rescue doesn't matter....?
ooooooooooKAY!!
Suzierose: You are spot on. You are asking the right question. The pharmacokinetics of melphalan are dramatically different between patients. It should be no surprise that the outcomes including toxicities are different from one patient to the next. Yet the SCT procedure still calls for a one-size-fits all dose of this toxic agent.
Dr. Anassie and his colleagues at UC are preparing a protocol to determine an individualized dosing regimen for melphalan. In this study we will take the differences in absorption, distribution, metabolism and clearance of melphalan into account. All that will be needed will be two blood draws the day before the SCT to determine the personalized dose. We hope to have the results by the end of the year of early in 2013.
Recommend holding off SCT until then (if you can)
Thanks Gary!
You hit the nail on the head of where I was going.
ADME is so variable with melphalan PK that it astounded me that a clinician would think that they need not wait..who even knows if the drug has cleared the body..such that the stem cells infused to rescue can themselves be subject to the same cytotoxicity as melphalan lingers in the system at 'conventional' dose vs the high dose originally infused.
And that is not even taking into account the delay due to renal dysfunction particularly in MM as well as elderly patients.
This just sounds like a reason for the insurance companies not to have to pay for another day in the hospital,....geeeez...
Call me paranoid, but having worked in a number of research laboratories, I have this dread about long-term stem cell storage: that over the span of 2, 5, or more years, the cells partly thaw out, owing to low liquid nitrogen levels, a sensor glitch, or other malfunction - if only for a few minutes, which is enough to severly damage then. How tight is the storage process?
I don't think waiting just 24 hours versus 48 hours is really that much of an issue. Even though there is quite a bit of variability between patients in how long melphalan stays in their system, it still is eliminated from the body very, very quickly.
As best I can tell, one of the most extensive studies so far of high dose melphalan and how long it stays in the body is the 2010 paper by Christa Nath and her colleagues, published in the British Journal of Clinical Pharmacology. The full text of the paper is available online here:
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2125.2010.03638.x/full
Figure 4 in the paper plots actual and modelled estimates of melphalan concentration in patient's blood over the period of four hours after infusion. Here's the graph:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2856049/figure/fig04/
Yes, there's a lot of variation in the concentration of melphalan in the blood in the first hour or two after infusion.
But, after four hours, the variation is basically gone because the melphalan concentration is also down to neligigle levels.
Given these results, don't you think it's fair to assume that, by 24 hours after infusion, little or no melphalan is going to be left in any patient's body?
Hi Everyone, and thanks Virginia for writing up these findings. When I had melphalan, my stem cells were returned to me the next day. At the time, I queried as to how long melphalan stays in your system. It would be somewhere between counter-productive to lethal, to have the melphalan destroy any of your new stem cells. Once the melphalan works on destroying the marrow, you are left with the blood cells circulating in your system already. They have only a limited life span, and so the new cells produced from the stem cells have to be produced before the old ones are gone, or else your counts go down so low that you will need blood transfusions. That might be one reason why the melphalan is given as soon as possible, as well as maybe saving costs on a hospital stay. The sooner you can get the new cells growing from the hematopoetic stem cells, the better. I was fortunate, and didn't require transfusions to help my system get the new blood cells up and running, but many patients do have transfusions and still have a successful transplant.
BTW, Suzie, I know you don't think a transplant would be of much benefit to you medically, and I sure respect all the research you have done to arrive at that conclusion. My auto transplant worked for me and I credit it as being part of my recovery to date.
Sorry...what I meant to say was that the stem cells are given back after the melphalan as soon as possible, in order to start groaning new blood cells in your marrow. Another thing that I found to be amazing, is that somehow the stem cells find their way back into the marrow! They don't just circulate in your bloodstream, even though that is where they are infused into. I wouldn't have wanted to be in the first groups of patients being treated this way, since there must have been a lot of trial and error, but now it seems that stem cell transplants can be given with a high survival rate. When I had mine, they said there was a 1-2% fatal failure rate...that was enough to make us very nervous about the procedure. I later met someone whose brother had died from an allo transplant...he had another type of blood cancer than myeloma. She was very shocked that i had had a transplant too. But of course modern medicine is actually improving all the time, in many regards, nest-ce pas?
Hi Nancy,
I don't believe in stem cell 'rescue' being perceived as therapy.
The therapy is lethal high doses of chemotherapy. Managing a life-threatening adverse event (AE) is not therapy.
What patients recover from is having their immune system obliterated from toxic lethal doses..not having their stem cells re-infused.
It is wonderful that high dose chemotherapy did worked for you. I believe that's great. When your own stem cells were infused back they kept you alive, but it does not constitute therapy, they did not do ANY thing to the disease. The high dose chemotherapy, melphalan was the therapy.
IOW's my issue is that patients think auto stem cell infusions are transplants that transformed their disease state when they do not. They rescue you from lethal doses of chemotherapy. I do not think it is fair that patients labor under the completely false delusion that getting their own stem cells infused is therapy. I think it is wrong that there appears to be little or no effort on the part of the medical community to inform patients that what they are choosing as therapy are toxic lethal doses of chemotherapy NOT a 'transplant'.
The euphemism of 'recommending' a patient have an auto stem cell transplant as therapy as wrong, and contributes to a patient 'selecting therapy' they believe is a 'transplant'..when in reality what they are selecting are lethal toxic doses of chemotherapy. And let's be clear, that is also what they are saying to other patients. " I survived the lethal doses, you can too"
I think we evolved here because patients when told the facts were not volunteering to be subjected to that choice as readily as when they wrong/falsely believing they were getting some innovative 'transplant'. A stem cell transplant is not therapeutic it is salvage.
If a patient chooses lethal high dose chemo that's OK, but if they are thinking the therapy is being re-infused with their own cells as a 'transplant' that's wrong. That stem cell infusion is essential to keep you from the life threatning side effects of the lethal doses.
Managing a life-threatening adverse event that results in a recovery period of years for the immunity system is NOT therapy. Many patients who endure those doses do not realize the long-term consequences of developing leukemia is also likely. But how could they when they think of the stem cells being re-infusion as therapy?
For me it is all about making informed choices.
Again the lethal doses worked for you and I am happy for you. Many patients do not have that outcome, even the IMF tells patients there is a 50% failure. Patients also then need to ask, what does failure mean in the setting of lethal high-dose chemotherapy with a rescue of their own stem cells? What it means is they do not achieve a CR. That is serious risks vs. benefits for each and every patient to know and weigh for themselves to make an informed choice.
Which is a love way of saying that lethal high doses of chemotherapy, would not be good for me, but I understood that was the choice. Stem cell transplant was not the choice.
See http://myeloma.org/pdfs/U-StemCell-Eng2011_f3web.pdf, page 32, column 2, question 2.
ANOTHER view:
Mary Degenkolb said:
I was on the study right after sct. I did not fair well with 5 mg of Revlimid.I was started just 3 months after sct, and I had the mucous and all the problems with reactions to Revlimid. I had the rash in the scalp, the sore mouth where everything “burned” to eat. Even water tasted like I was drinking the hottest hot sauce available. So they stopped the study and took me off of the Revlimid unit I get more immunity and then will reset with 10 mg for maintenance. I will start back on the maintenance regime in a couple of weeks. Reading the information above, worries me. I, to this day do not know what I was facing in the form of what the cancer was doing to me. I only know that I was told I have this disease and I have this route of treatment. I guess that since I had taken 25mg of Revlimid prior to sct and was in remission with that course of treatment, the Dr. figured that I should be able to handle the lower maintenance dose. I do know that I was staged as III (three) and was told that sct was my only option. I have also been told that Revlimid is my only medication to continue my remission that I am currently in. The Dr. said that if the issues continue with the Revlimid, then there is no other option. Is there any other treatment other than the Revlimid regime listed above
http://www.myelomabeacon.com/news/2012/05/11/revlimid-lenalidomide-maintenance-therapy-studies-clarify-benefits-and-risks/
Hi Suzie, Nice of you to reply, and it's fine to agree to disagree too! I too really hope for better, more humane treatments to control and dare we hope 'cure' MM. It is just such a horrible disease to have in the first place, and there are now several approaches to management. Part of your treatments depends on where you live (i.e. what country), and basically what treatments are accessible to you too. Finances are obviously a factor ...the whole thing gets people into a quandary and dire straights often. Any of us who have cleared the first hurdle of getting into a remission, by whatever treatments available, are among the luckier ones, IMO. Always enjoy studying the latest research, as far as I can understand it, with my rusty old BSc in Microbiology (1974). I do gather that you are an active working scientist....are you on a leave right now? Have a nice weekend!
Hi Nancy,
I think I have you beat on rusty. I retired in 2001 and my texts are older than yours...lol.
You have a great weekend too.
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