Arnie’s Rebounding World: The Donor Transplant Day 60
It is now day 60 following my donor (allogeneic) stem cell transplant, and I wanted to give an update on how it has gone and what is in store.
As with an autologous (self) stem cell transplant, everyone talks about the first 100 days as the critical period. This is true even more so with the donor transplant.
As I mentioned in my last column about my transplant, the intensity of the treatment, the need for close monitoring, and the number of things that can go wrong seems much greater with the donor transplant.
After my donor, a 21-year-old female from Germany, was found, I was admitted to the hospital to begin high-dose chemotherapy and immunosuppressive medications.
The chemotherapy was melphalan (Alkeran); the same as what is frequently used for autologous transplants. The side effects are the same, regardless of the type of transplant, and included extreme fatigue, diarrhea, nausea, and loss of appetite.
Fortunately, as the nurses advised, sucking on ice during the melphalan infusion was extremely helpful at avoiding mouth sores.
After five days of chemo and a day of rest, I received my “transplant,” an infusion of a bag of donated stem cells.
Then the waiting began for engraftment, the process in which the stem cells take hold and start to build a new immune system. This usually takes about 10 to 14 days, during which you are extremely susceptible to infection.
For me, this period went fairly smoothly, just requiring support with fluid, blood, and platelet transfusions. I started to engraft around day 12, and my white blood cell count started to recover.
That’s when the problems started to hit. It seems everyday brought a new issue to address. The doctor’s common refrain was, “Oh yes, this is common,” or, “We see this sometimes.”
First, as we were starting to talk about discharge, I was delayed by a fever. I then developed shortness of breath and chest tightness, due to fluid around my heart and lungs. It was decided that this was a side effect of the chemo. “We see this,” I was told.
The two immunosuppressive medications I took were Prograf (tacrolimus) and Rapamune (sirolimus or rapamycin).
As a side effect of these medications, I developed something called thrombotic microangiopathy or TMA. This is a build up of strands of fibrin in the blood vessels, forming a net that causes blood cells and platelets to break apart. This can be a very serious problem, causing kidney problems, increased transfusion requirements, and jaundice.
Fortunately again, this was caught early. Changing medications reversed the problem. “This is common,” I was told. “We see this.”
Next came an episode of atrial fibrillation, where my heart went into a rapid abnormal rhythm, causing my blood pressure to drop and sudden dizziness. Again, fortunately this resolved by itself in a couple of hours. “This is common. We see this,” I was told.
After two previous autologous transplants, I knew this donor transplant was a whole different ball game.
The transplant team did a great job of addressing every problem quickly, and things finally seemed to settle down. I was discharged on day 17 after my transplant.
In the period after discharge, there are two main issues to worry about. One is infection; the other is graft-versus-host disease, where the new donor cells identify the body as foreign and attack the body’s healthy cells. Follow-up at the clinic begins on an almost daily basis.
Graft-versus-host disease comes in two types: acute and chronic. Acute graft-versus-host disease usually begins around day 30 and can occur during the first three months. Chronic graft-versus-host disease can show up three to six months down the road. Acute graft-versus-host disease most commonly attacks the skin as skin rash, the gastrointestinal tract (causing diarrhea, nausea, and vomiting), or the liver.
In my case, I was doing great until about day 40, when the skin rash stared to hit. It began with some itching and flushing of my face, and then it attacked me full blown on my abdomen, chest, and arms with a raised, red rash and irritating itching.
I have been told over and over again that some graft-versus-host disease is good. It is thought to be accompanied by the graft-versus-myeloma effect, in which the new immune system fights any remaining myeloma cells.
The treatment was topical steroids and to increase my immunosuppressant medications and oral prednisone. The increased immunosuppressant medications and prednisone do, however, increase the risk of a serious infection.
The increased meds seem to be bringing the rash under control. In order to try to get off the steroids, my doctor has proposed a novel next step.
It is known that Velcade (bortezomib) has an anti-graft-verus-host effect and has been used for this purpose. Since I have been very refractory (resistant) to Velcade, he has proposed trying Kyprolis (carfilzomib), both for the graft-versus-host effect and the anti-myeloma effect. It has not been tried yet in this setting, but everything seems to indicate it should work. I am game.
Even as a physician, I am continually impressed with the complexity of the donor stem cell transplant process and the number of potential complications. Every decision the doctors make is walking a tight rope of competing factors.
In the mean time, I am feeling good and regaining strength and energy. I am trying to get out and about a little bit but am very cautious about exposure to crowds and germs.
Arnold Goodman is a multiple myeloma patient and columnist at The Myeloma Beacon.
If you are interested in writing a regular column to be published by The Myeloma Beacon, please contact the Beacon team at .
Wow... what a story!
Interesting take on the rash. I had a nasty one after my ASCT that was quite bad for about 9 months... it's not totally gone yet, but nothing like what it was before (I'm just about 13 months out now). I was told it was a reaction to the med I was taking prior and after the Melpahan to allay the mouth-sore issue.
Best wishes going forward, Arnie!
Dear Arnie,
Thank you for sharing your experience. I look forward to your next installment.
My very best wishes to you.
Lin
I promised myself after my stem cell transplant, never again! Now you have had three, with this last one a ST on steroids!!
God bless you. I'm praying for you.
Julia Munson
Hi Arnie,
Hang in there. It is amazing what the body can actually put up with.
I had an autograft July 2010 (melphalan nearly killed me) and this didn't really have any affect on my "refractory" myeloma. Then I had an allo in April 2012 (100% HLA matched non-related donor with different blood group). They conditioned my body with reduced chemo and low intensity TBI. So for a while I was a chimera, 76% donor and 24% me. All went well until I caught an adenovirus 6 months after transplant (i wasn't on any immunosuppressors). My immune system went crazy and I had severe liver GVHD (stage 3/4)as well as skin (the drs weren't so sure about it in my lungs). As a consequence my myeloma is now in remission (fantastic)but I have developed GVHD on the fascia (not so fantastic). I am still taking immunosuppressors (prednisolone, cyclosporin and plaquenil)which keep it under control and I probably will be taking them for a considerable time. At the moment my liver and kidneys are doing fine and I try to avoid people with colds. It is a tightrope that I am walking on but I am glad that I am able to balance on it. I sincerely hope you find your balance.
Thanks everyone. Libby sorry to here about your GVHD experience but glad you are doing better. It really is like walking a tight rope. I am very interested in the experiences of others post allo, as they are all so different. I had a non-myoablative conditioning regimen just short of a full ablative dose of chemo, and had a matched unrelated donor (MUD)
I am fully engrafted with 100% donor cells.
It s very important that people understand the distinction between the allo (donor) transplant and the auto stem cell transplant (ASCT) . That is really the point I am trying to make in my last couple of columns.
They are two very different animals with very different sets of issues and problems and very different management. Even a skin rash will have totally different implications in an allo transplant vs an auto transplant.
It's always very informative to read your medically scientific columns, Arnie! Did you also practice oncology when you worked as an ENT specialist? I think you could write a book on myeloma by now...hope you have a REALLY peaceful month with no medical complications whatsoever!
Nancy, a portion of my practice was Head and Neck Surgery so I was very involved in the diagnosis and care, especially surgical, of patients with Head and Neck cancer. But I am not an oncologist and worked closely with oncologists and radiation therapists in the care of those patients.
I am hoping for a peaceful month, so far so good!
This is 'off topic' as far as myeloma goes, but when one of my daughters did a 'rotation' in ENT surgery, she told us of all the cancers that are treated. Hats off to those surgical/oncology/radiology teams also! Really, I have the greatest admiration for everyone working at the cancer centres!
Thanks Arnie for the information on allo transplants. I had asked a few mons ago if anyone had undergone allo but got no response. I had an auto in 2010 with an m-spike of .03. I was on no treatment until Feb of this year when my m-spike jumped to 1.1. My transplant physician had already found an unrelated donor with a perfect match. I also have chromosome 13 . He immediately started talking about the mini allo. I wanted to go to hawii so we didn't talk about it this summer. Then he explained everything that could go wrong and it really scared me. I am just getting my life back sort of and not ready to go though these things yet. As I understand it, these things have to happen for the graft vs myeloma effect to take place. My kidney function is ok but my creatine is between 1.5 to 1.8 and he says this my be a problem. Are you able to function fairly normal?
Auto vs allo, they are two different beasts. For me the allo has saved my life the auto nearly ended it. If I had my time again (hindsight is a wonderful thing) I would have gone straight for the allo even with the complications I am experiencing with GVHD. My allo conditioning treatment was done as an outpatient - I didn't spend any nights in hospital (but had to be close to one) until I caught the cold 6 months after the transplant.
Music meme the unknown is scary. I was scared & worried but the choice was to die from MM (the available chemo wasn't controlling it) or to give the mini allo a go. My choice was simple.
Thanks Libby C, these are the responses I need to hear. I am an only child so my physician is really excited to find this perfect match for me. Trust me I want to live at all cost. I have 3 children and 9 grandchildren and I want so be involved in every aspect of their lives. My cobra is ending so we will be switching insurance . There is a lot of THINGS I have to take care of but still deal with the daily reminders of the myeloma. Med, did I drink enough fluids . I have a huge history with asthma and my lungs and infections so that has to be taken care of. Really being aware of whom I come in contact with. I really can't complain because I have had several bouts with death dealing with my lungs and God has brought me through all of them. You said you were conditioned with lows chemo and RBI, how was that?and how long did it last before you achieved CR.were you able to learn anything about your donor ?
Hi Music meme hope I can be of some help. I was 43 when diagnosed with 2 young children so can understand your desire to stick around for your children and grandchildren. With regards to my MM I dont know which chromosomal abnormality I have as each time I had a BM biopsy there weren't enough cells for analysis.
Basically my allo was an experiment. The reason I had low chemo and reduced intensity TBI was because I had two MM specialists (both Professors - they work at different hospitals in Melbourne, Australia) disagreeing on what my next treatment would be (My MM would not stabilize with any of the available chemo). Or whether there was going to be any treatment (We actually had to tell our children there was no more treatment - dreadful week). This was because I had nearly died from the dose of melphalan prior to my auto (heart, lung, kidneys and GI tract) and normally melphalan is used in conditioning for an allo. But as luck would have it I had two perfectly matched donors - I think those donors were like a carrot dangling in front of the Profs noses. As I was relatively young and even though my body had been put through the wringer I seemed to recover quite well so the question for the Profs was how can we condition her body to accept the allo without killing her in the process. So I was an experiment.
6 months after the allo was when I got sick and developed GVHD. From this time to CR was approximately another 4 months. My donor was from Washington thats all I know.
As I have achieved CR, although I do have GVHD issues, the Prof is now using the same conditioning regimen on other MM patients.
I´m glad to hear you`re doing fine! 100% donor cells, that is fantastic!
I am on the same immunosuppressive medications as you were (or still are?),tacrolimus and sirolimus, and has been told that with these medicins GVHD usually starts around day 40.
I´m now on day 27 and also doing fine. So far my only problem has been nausea, loss of appetite and an infection in a tooth that antibiotics took care of.
Have you been monitored yet for disease status? When did you first check for chimerism?
Best wishes from Åsa
Thanks for this post... it reminds me a lot of my own allo transplant about two and a half years ago for ALL. I went through it while in grad school, if you can imagine how much that must have sucked. Today, I have my PhD and a great job that I struggle to maintain: chronic GVHD is way worse for me than the initial stem cell transplant.
I constantly feel weak, achy, and in pain. One of my hips has failed and been replaced due to chemo-induced avascular necrosis (18 months after the fact - just something to watch out for FYI); the second is failing now and I'm going to see my orthopedist today about getting it replaced. I try to lead as normal a life as I can, but it takes so much of my energy to break routine that it usually isn't worth it.
I find myself constantly reminded of the person who I used to be. It's not remotely who I am now. My memory is much weaker than it used to be, but my doctor doesn't even attempt to address it when I bring it up. It didn't take me long to realize that my doctors are almost as in the dark about what's going on with my body as I am, so I find myself scrambling to understand why they're prescribing what they're prescribing at any given time so that I can apply it (or not apply it) in real time to my changing body. Once you start screwing with your body's natural function through transplantation and medication, you can't stop. Your body starts to feel like this bizarre chemistry experiment, and you just have to make your best guesses at what will keep it going.
I hope that you have an advantage here as a medical doctor; my computer science degree has proven almost useless. The medical industry isn't overly fond of computers... I was lamenting the fact yesterday that they don't communicate with me via email so that I could have a record of the things they tell me.
Anyway, I hope that what I've described of your future isn't too bleak, but I see no reason to give you much hope, either. I went into my transplant thinking I would finally be getting better, but part of me still thinks I would have been happier if I had never been diagnosed in the first place.
Dear Dr Goodman, Thanks for your update. I am so sorry to hear about all your complications & wish you a speedy recovery. On your last column early september I wrote to you telling you about my situation w/MM. I too had 1 auto t/plant & was succesful with velcade but have been advised by 2 out 3 oncologists to proceed with the Allo t/plant. I lve in Montreal & it seems Europe & USA are much further in knowledge than here. I meet with the allo t/plant team in November to discuss my situation. I was kind of on the "fence" decision-wise about doing the "allo" but after reading today's update & other comments I am very fearful & considering NOT doing this. I am in remission right now & have been lucky that I have had no serious side effects with Velcade,Melphalan or the auto t/plant but to risk all this where no other organs are affected with cancer or anything else ....to do an allo t/plant right now to me seems I should be declared insane to risk this. When I meet w/ the allo team I am certainly bringing all these postings with me to make my presentation to them. Thank you again Dr Goodman and look forward to your next update.
Hi Dr. Goodman,
Glad to hear you are doing well. I actually do not think they should discuss autos and allos in the same sentence. They are definitely two entirely different "animals", that is for sure. Did they ever discuss using ATG with you? I also had an unrelated female donor for my transplant. I am surprised to read that few patients seem to use ATG. The other advantage, other than the obvious of greatly reducing the chance of extensive chrinic GVHD, is that I was able to use less Prograf and get off of it right on schedule, at 6 months. It also spared me of using any steroids after my transplant. I am grateful that the only steroid I have ever had to use was DEX during my 4 cycles of induction. One of the reasons I think I am doing so well from a QOL standpoint is that my Doctor did not make extensive use of steroids during my treatment.
Mark
Asa , glad you are doing well. I was initially on tacrolimus and serolimus but had to stop the tacrolimus because of the TMA complication. I am now on serolimus ( Rapamune ) and Cellcept and prednisone. I was checked for chimerization by blood test on day 30. Myeloma labs were also done but I am told it is best to assess the myeloma response at 90 days.
Music Memei think some of the other posts address your question, which is really what is quality of life like after an allo transplant? And the answer is that it is all over the board. Some people do great, some people continue to have ongoing problems with GVHD which can be very problematic. Some people may die of infection or other organ complications. But techniques are improving all of the time. There is no easy answer. It also comes down to what is the alternative? Is it worth dealing with Some GVH to be alive? To me it seems like the risk and trade off is worth it but everyone is different and we will see in 6 months or a year from now, or with great hope 2 or 5 years from now.
I have no experience with ATG, it doesn't seem like they use it much at Moffitt but I haven't had a chance to ask anyone about it yet.
Hello Dr Goodman
Glad to hear that the transplant team at Moffitt have been taking good care of you and were quick to address and treat each issue as it arose.
It is wonderful to read your updates and hear that you are doing well. Your strength and determination will help you overcome any bumps in this myeloma road.
I am personally interested in your myeloma experience and I find your colum very easy and informative to read.
When I was initially diagnosed at aged 41 I tried Revlimid,Dex,velcade as induction with no response, then tried Cytoxin, again with no response. Next came Thalomid and VDT PACE with no result. More recently a auto transplant with VGPR and finally a 2nd auto to finally reach CR. it's been a long 2 years. I have had a 6 month drug free holiday and will be starting maintenance with Kyprolis on Monday. I am yet to find anyone using Kyprolus as maintenance. I do know that if there is any relapse I will be joining the allo club !!
Continue your wonderful writing but above all continue to get better every day.
You are right Dr Goodman, techniques for allos are improving all the time. But they can only continue to improve if patients are having them. At the moment due to the huge implications of GVHD and its unknown quantity with respect to QOL most people will only have an allo when it is their last option. At the moment QOL for people after allos is "all over the board". However I think that if I had to have my treatment all over again I would opt for the allo first even with the GVHD.
How encouraging! Wishing you all the best!
So courageous of you Dr.Arnie to share your experiences.My husband was diagnosed withMM, in March2012. He has finished 2 cycles of CyborD and has received his autologous stem cell transplant this past Tuesday. He is feeling some of the effects now but he is staying positive. We will keep reading your columns.
Wow, what an insightful thread of comments and experiences. My husband was diagnosed 8/2011. We did 2 rounds of VCD then two rounds of VCRD. He still didn't achieve CR. He had an auto transplant done in January, 2012. He did great and was home day+11. He was still not in complete remission but in July, his number was down from 0.6 to 0.12.
Docs said, come back in October and enjoy your summer. We were cautiously optimistic.
Today, his number is back up to 0.63 only after 9 months of his tranplant.
It's devastating.. we were hoping for MM to go away completely but here we are again. He is going to do 21 days of RD maintenance but we are discussing an allo. He is 43 years old. We have not done any of the other therapies that other people have done. And I'm getting different opinions on whether to do this now or later based on reading the comments here.
Our doctors think this is his best option for a long term remission. They seem to think that at the end of the day, he will need it anyway. Better to do this now while he is otherwise healthy and strong. He has a perfect sibling match. But I am scared of the effects of GVHD after the allo. Are we jumping into this too soon? To those who've had an allo, in hindsight, would you have done it sooner rather than later?
Hi Letsbeathis,
Hindsight is a wonderful thing and I would have gone for the allo sooner rather than later.
Yes I do have GVHD and I do need to take medications to keep it under control BUT I also have to take medications as a result of a failed auto. In terms of QOL so far I prefer the restrictions of the GVHD rather than all the side effects (particularly peripheral neuropathy) from thalidomide and velcade.
My allo transplant used low dose chemotherapy and low intensity total body irradiation.
In response to another post Mark posted this, I found the paper very informative.
"Stem-cell transplantation from allogeneic donors may be curative for 10–20% of patients with chemotherapy-resistant, refractory hematologic malignancies, and for up to 80% of patients who are transplanted in remission. Much of the high response and curative potential of allografts is attributed to a ‘graft-versus-tumor’ effect. In patients with multiple myeloma this effect has been well documented.[3–5] In contrast, stem-cell transplantation from autologous or syngeneic donors provides little or no immunologic effect against the myeloma cell. Thus autologous or syngeneic stem-cell transplants are mainly a form of supportive care and require intensive chemotherapy with or without radiation to accomplish eradication of the disease or alternative strategies designed to duplicate or mimic the graft-versus-myeloma effect. Long-term follow-up of recipients of autologous stem-cell transplants indicate a continuing risk of disease recurrence after 5 years, and arguably few if any patients are cured. In contrast allogeneic stem-cell transplants with long-term follow-up appear to result in durable remissions and a lower risk of recurrence after 5 years."
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3017399/
Good luck
Has anyone found any supplements that are helpful with side effects? My husband is newly diagnosed and will be starting the cyBorD protocol? after some radiation to his L3 before it does any damage to spinal cord.
Thanks.
letsbeatthis, I can completely feel your pain. This is a really difficult decision to which there is no good answer. Allo transplant, while it can be successful, is a scary and daunting proposition and it is certainly not without significant risks and problems. It least for me personally I felt that I had pretty much exhausted all my other options, but everyone is different. It does sound as though you still have other drug options including the next generation of novel agents such as carfilzomib and pomalidamide and other drugs available through clinical trials. Although even these are not always amazing. The article referenced above is helpful as well as several recent ones in the myeloma beacon. Try to get as many opinions and as much information as you can. Good luck
Arnie, thank you for taking time to answer my post. I really appreciate it especially since you are recovering from your allo. I hope everything is well and that things are looking more positive for you.
I will ask more questions the next time we see our doctors and will definitely continue reading the articles here.
LibbyC, I am going to carefully read this article you have added to your post. Thank you for sharing your experience and challenges. I wish you all the best in your journey to beat MM.
Randy,
Thank you very much for your honest feedback, it was needed, I feel what you say about the long term consequences but I do not have the real experience to back up those feelings.'
So, I truly thank you for sharing my thoughts without having been there!
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