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The Role of Stem Cell Transplants in MPN Treatment

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Published on September 9, 2021

Understanding Stem Cell Transplants for MPNs

An in-depth look at stem cell transplants, their current role in MPN treatment, and the role they will have in the future. In this live Answers Now program, host and MPN patient advocate Ruth Fein is joined by Edward A. Faber, Jr., DO, MS, Medical Oncologist, Hematologist & Transplant Specialist at OHC Specialists in Cancer and Blood Disorders, to discuss who is eligible for stem cell transplants, the risk of complications, and new treatment alternatives.

Support for this series has been provided by AbbVie, Inc.. Patient Power maintains complete editorial control and is solely responsible for program content.

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Transcript | The Role of Stem Cell Transplants in MPN Treatment

Ruth Fein:
Hi everyone, thanks for joining us today for our Answers Now series on myelofibrosis, one of the myeloproliferative neoplasms, or we call them fondly, MPNs. I'm Ruth Fein, I'm a health and science writer, and I'm someone who has lived with one MPN or another for about three decades. I've also become a patient advocate, which gives me great pleasure to be here today. We're with Dr. Edward Faber today, a transplant expert at OHC Cancer Center in Cincinnati. And we're here to talk about everything transplantation as it relates to MPNs, of course. Welcome, Dr. Faber.

Dr. Faber:
Welcome everyone. It's very nice to be a part of this discussion this evening, and hopefully depending on where you are, it's not as steamy and muggy as it is here in Cincinnati in the dog days of summer.

Ruth Fein:
Well thanks for spending some time with us today. We have a really good-sized live audience tuned in right now from across the US and across the pond, in fact. And they're all here for one reason or another, some connection to transplantation. They're either people living with an MPN, or there's someone who's a caretaker for someone, or whatever the reason, they have an interest. And it should be an interesting conversation today. So, let's get started. We're talking today about the only complete cure for myelofibrosis, and indeed any of the MPNs, and that's a stem cell transplant. So first, Dr. Faber, would you put into lay terms exactly what a stem cell transplant is? So, what's the difference between this type of transplant that we use for MF patients versus some other types of bone marrow transplants that we hear about.

What Are the Different Types of Stem Cell Transplant?

Dr. Faber:
This information comes forward to all of us seemingly at lightspeed, especially on the internet and all the other information that we have access to. I will say that sometimes, we as transplanters, we use terms interchangeably and probably not entirely correctly for simplistic purposes or whatever those reasons may be. And so, when we talk about transplant, there are terms like hematopoietic cell transplant, stem cell transplant, bone marrow transplants, peripheral blood transplants. To narrow it down and to make it easy, we are able to collect stem cells from patients or donors, for example, and where we collect the stem cells from is how the designation should be. So, you can't get into trouble if you call it a bone marrow stem cell transplant or a peripheral blood stem cell transplant. And so, sometimes we do mobilize and collect stem cells that are circulating in the peripheral blood through a filtering process we call apheresis.

And that's a peripheral blood stem cell transplant. When we go back to the operating room and directly remove bone marrow from a patient, that's what we term as a bone marrow stem cell transplant. Both of those are applicable for our patients with myeloproliferative disorders or myeloproliferative neoplasms. And so, what makes this a little bit different is that we do require a donor because the stem cell and the environment of the bone marrow is the root of why we have MPNs. So, we do require a donor in collecting stem cells, either from the bone marrow or the peripheral blood, and then infusing them into the patient after we condition the patient, for the most part, is a chemotherapy regimen.

Ruth Fein:
Right, thanks for the explanation. I think it's worth repeating because it is confusing. And as you said, terms are used interchangeably. If you'll help me keep this in perspective for people, do you have an estimate of the number of stem cell transplants that are done in the U.S. for people suffering from PV or MF? And if you want to put that in perspective, a percentage of people with the diseases that go on to stem cell transplant?

Dr. Faber:
The majority of transplants are for acute leukemia, MDS, and when I say those terms, that's the allogeneic transplant where we utilize stem cells from a donor that I had just explained. Most of the time in most centers that I'm aware of, your number of transplants are probably around 10%. Now, there are some centers that may do transplants for MPN a little bit better than others and patients gravitate to those areas, or it's just variable based on the incidence of MPN in the community that surrounds your transplant center. So, from out of all hematologic disorders or malignancies, MPNs usually, in any community, are around eight to 12% of hematologic disorders. And that's a number that you can dispute a little bit, but again, I think it just depends on the demographics and the incidence from state to state, city to city.

Ruth Fein:
So we know that some people, myself included, can have fairly benign disease for a very long time. And then in that case it progresses slowly. And then experience a very quick change in their symptoms and their condition. When does it make sense for people to speak to their doctors about transplantation?

When Is the Right Time to Consider Transplant as an MPN Patient?

Dr. Faber:
Yeah, absolutely. And if you know, or anyone viewing tonight knows, the absolute answer to that, I would certainly welcome an opportunity to educate. Because you're correct, it is a very heterogeneous process for each of the MPNs, whether it's PV, ET, myelofibrosis. There's variability among each of those. And then, some of the other subsets and less common MPNs variability there, like CMML, for example. In the past, when I was starting this, about 15 or more years ago, everyone got a workup and usually going to the transplant center was when you thought things were not following the textbooks anymore. And you're exactly correct, there are folks with myelofibrosis, for example, they can have five, seven, or more years, sometimes longer, before things start to affect the blood counts. The quality of life with fatigue and change in appetite and night sweats, for example. Itchiness, with our patients with PV.

So we've had some help lately in certain testing that we refer to as molecular testing. There are a variety of labs out there that do next-generation sequencing that we refer to. But we've identified certain molecular markers that offer us a forecast or a prognosis as to maybe when the process will evolve into, say, the white count decreasing or increasing, patients becoming more anemic, having lower platelet counts and maybe the onset of some of those constitutional symptoms. And that helps us, as transplanters, maybe regarding the timing. So, I have on my phone things I can't remember, and some very nice charts that help me interpret this testing with the other characteristics that the patient has. And we do know that there are certain mutations, like things called ASXL-1, for example.

If you have that, then we probably need to think of transplant a little bit earlier, say in three months, six months, a year, instead of maybe trying to wait three or five years. Because the chances of those particular disorders turning into something more, like acute leukemia, is much, much higher. So, it is an evolving process. I think it's not just going to a transplant center but going to a center that has someone dedicating their career to MPNs, because they certainly can chime in and make sure that some of this additional testing can be done a bit earlier. And for me as transplanter, yes, we sometimes have to do that, but if we have somebody that has been to a higher center that has an MPN expert or someone that dedicates their career, a lot of times they then can refer to us that way too.

Ruth Fein:
Does it make sense to have the conversation early on, as that sort of just in case, so it doesn't come out of the blue if it's a serious thing that people need to consider? How early is too early? Or does it depend on the progression or state of disease?

Dr. Faber:
You may hear from a lot of transplanters, there's never such thing as anything too early. But it's a way that you can follow the course with your patient because eventually they're going to become your patient too. That works really well when you have a good relationship with your referral practices and centers. So, as an example, we've had a patient over the last year. He was being managed by his local oncologist who refers transplant to us, brings him to our attention about five years ago. So, we see, and we check in about once a year and his molecular profile did forecast that he probably didn't need an upfront transplant, within the first three, six, or 12 months. We did follow along with his primary oncologist for about four years and then that's when his molecular markers were forecasting that constitutional symptoms were going to arise.

And there was a trial with Jakafi (ruxolitinib) and then the second generation JAK inhibitors and then we moved him into transplant. So that worked very well. I would like to say that that happens with every patient, but sometimes it doesn't. And as a transplanter, I look at that as, we left the patient uninterrupted for about four years. So, all the side effects, all the complications, a good quality of life. He owned a construction company, he was able to pursue that, and we were able to leave him alone there for a bit before moving him to transplant.

Ruth Fein:
So thanks to research and evolving best practices in disease management, people are being diagnosed and sometimes treated earlier in their disease, right? So, do you think that, in some cases, that could prevent the need for stem cell transplantation later?

Dr. Faber:
For older folks, now older is a term for a discussion, but there are folks that I look at that may have other health issues beyond their control that, yes, in years past we had to go to transplant. And if they didn't have a good outcome, and they succumbed, unfortunately from complications, I don't know that we always benefited people like that. But with the JAK inhibitors and the other classes of medicines as they're coming forward, you can have improved blood counts, you can improve constitutional symptoms, and for many people for a number of years. And so, again, as a transplanter, I look at that as, we avoided toxicities and side effects and very serious problems because of transplant for a number of years. And I take that as a positive and a win in those patients. When patients are above 60, if they're 68, that can be very good years with very good quality of life.

Ruth Fein:
Yeah, let's hope so, right? Let's talk more about transplantation earlier in disease progression and then I'd like to go back to the more aging population. I hear more and more about people with MF and PV deciding to have a transplant earlier when they're younger and healthier, is the point and the idea. And that's, of course, waiting until they aren't as strong or waiting until they have complications that don't offer them as good of an outcome. What are you seeing as a transplant specialist?

Dr. Faber:
It's a journey in decision-making. And as I like to talk to patients, you need three things to have a successful transplant. A blood disorder that's amenable to be treated and/or cured, a good donor, and then adequate health. And so, there are times that maybe the MPN or another health issue gets on top of you, and you can have the patient recover from that, and then be healthier heading into transplant. That is a concept, I think regardless of age, whether you're in your third, fourth, fifth, sixth, or even seventh decade. The earlier transplant, I believe where the advantages are, is with the next generation sequencing, that molecular testing. Doing the transplant earlier, before you have, say acute leukemia. Because if you move into acute leukemia, then you have to have true chemotherapy, you have to deal with the side effects and the complications.

So you may enter the transplant process, may be not as hardy, so to speak. And that causes more time to heal afterwards. So, the other way to look at this too is that, again, I always really try to make good decisions because if you move somebody a little bit too fast... I'm a transplanter, I think of the negative outcomes that you can have with transplant. And I hate to think about moving people too fast and then having a bad outcome, having patients die, because of anticipated outcomes. The risk of dying in the first year, especially under the age of 60, is still around 15 to 20% with a good donor.

You hate to deprive people of good quality years because you moved a little bit too fast. So, in my mind also, it's the type of donor that you have. If we all had a young, related, male donor, that's where some of the side effects are less. If you have unrelated donors or mismatched donors or now haploidentical or half matches, your risk through transplant keeps going up. So, every once in a while, if you are able to treat symptoms, improve blood counts, you may be able to jockey for a little bit of a better donor also. So that would be another maybe argument against going earlier into transplant.

Ruth Fein:
Well, thank you. I'm starting to get some questions from our audience, and a lot of them are really about what to expect, so let's try to put them together. So, if we get into the nitty gritty details of transplantation, people want to know what to expect if they have to have a stem cell transplant. Or even if they're first considering it. So, let's jumble all this together. How many days can they expect to be in the hospital and then in further isolation? What are the biggest risks during and after the process? And let's break that down, because we're getting lots of questions about, how is it different for the aging population versus a younger population. So, walk us through that, if you would.

What Can You Expect During and After the Stem Cell Transplant Process?

Dr. Faber:
Yep. So, I had a mentor years ago explain that it's a process that changes your life forever. And I really liked that phrase because it changes your life forever in ways that you understand, and in ways, sometimes, that we don't understand. And so, in ways that we understand we can predict tiredness and fatigue and diarrhea, and it can be very severe at times. Two, three liters of stool, very liquid-y. We have ways to help with those symptoms, but they necessarily don't always take them away immediately. So, the 30-to-35-day period after you receive your high-dose chemo, and then your donor stem cells, it's probably a week of just general decline, appetite, activity decreasing. When the blood counts go to zero, so to speak, most people are dependent on blood and platelet transfusions. But the tiredness is still something that I don't think I still fully have understood how to explain.

It's like having the flu, the worst flu of your life, I’ve used. My patients have returned and said it is different, life is smaller and slower. It takes you a little longer to get your day started, to get into your normal clothes. Takes you a little longer to eat. You eat less. It takes you a little longer to walk around the unit. And some days you may not walk out of your room, but just get some activity inside of your hospital room. Somewhere between days 15 to 25, maybe up to 30, well the blood counts start to return. And depending on if you have a related donor, if you have an unrelated donor, if you have stem cells as your source, that recovery may be a little bit faster. If we used bone marrow as the source of your stem cells, the count recovery can be a little bit longer.

As we know, many folks may have an enlarged spleen, and so that slows down how platelet counts recover. So, bruising, nosebleeds, bleeding when you do your oral care around the gums temporarily, these are things that can persist. I think for most folks, generally speaking, days 10 through 20 are the most challenging. Maybe not eating as well, you can have mouth pain and mouth sores, throat pain, the whole GI tract does get affected. And so, eating can be a challenge and sometimes we supplement that with oral nutrition, sometimes feeding tubes, sometimes intravenous nutrition. Those are days that it's, as I mentioned before, smaller and slower is an analogy that I like to use. It's much different than the way that folks were living, coming into this. But it really is a day-by-day journey until counts start to recover.

We do have to worry about fevers and infection. And when blood counts are low, the fevers can really affect folks, causing a lot of fatigue and not spending much time, say, out of your bed. Maybe bed to the bedside chair, or depending on your program, if you have a little place to lounge there, and a small couch, that's a good day of activity for a lot of folks. And again, it is a tough journey and it's day-to-day. And that's where I like to try to explain to patients, it's a day-to-day journey. Let's not think about a week from now and a month from now. Let's get your counts recovered, address fevers, diarrhea, side effects. Get you feeling a little bit better then think about the next steps and getting out of the hospital, about 30, 35 days.

Ruth Fein:
Pretty good synopsis. I think it answers a lot of questions. A few more questions that have come in, do centers of excellence differ when it comes to the conditioning regimen for transplant? This is in particular for secondary myelofibrosis, but the question is really general.

Dr. Faber:
So conditioning regimens, there's a very large chart in our literature. There's probably about 15 to 20 that are out there. This is where I think it's the center's responsibility to follow their own outcomes. So, is one conditioning regimen better than the other? Some of the principles, the answer to that is yes. But at the end of the day, I think it's up to each center, and our center is the same way, we look at our outcomes. And as I do this a bit more, some of the better centers, they keep it simple. Instead of choosing between one of seven conditioning regimens, they focus on mastering, say, two or three. And then they can control the side effects, we can control our outcomes, we can help folks recover and heal. Especially once you get out of the hospital, get your endurance forward.

So there's not necessarily one or two that I think work best. That's why many centers have their research interests, and they will use a conditioning regimen on a protocol in order to compare it and see if they can improve what we already do. Our folks under the age of 60, there is something we refer to as myeloablative regimen. That means that after those doses of chemo, there is little to no chance, really no chance, of ever recovering your own ability to make your own cells. Over the age of 60, we use reduced intensity, myeloablative regimens, which lower that to make side effects better. There is a cost to that. The chances of the MPN returning or going to leukemia is a bit higher, but again, it's risks and benefits. So, there are regimens that use drugs with busulfan (Myleran and Busulfex) and fludarabine (Fludara) and melphalan (Alkeran) and Cytoxan (cyclophosphamide) that I think that are more common, generally, than others.

Ruth Fein:
So another question that just came in, what are the actual statistics about mortality from MF transplants? And I'd like to switch that to the other side as well, what's the mortality, but what's the rate of success and how do we define success? Is it only when you're completely cured or are there different levels of success?

Dr. Faber:
So age is a predictor. Also, what is the status of your MPN? Say, your myelofibrosis. How many blasts are there? Where is this in the journey? How close does this look to a normal marrow or acute leukemia? As we look closer to acute leukemia, the chances of leukemia returning after transplant are higher. The other factors for success are the presence of a viral infection that we know as CMV. So, there are a few scoring systems out there. There's one that was discovered and followed by the Fred Hutch in Seattle called the PAM score. And so, in addition to that, do you have a related donor? The sex of that donor? An unrelated donor? Haploidentical, half match, so to speak. So, as we, say, get away from a fully matched male donor with very little blasts and, say, negative CMV exposure of both the patient and a donor… As we get away from that and, say, towards haploidentical transplants where both parties have been exposed to CMV infections, whether they're active or not, blood type mismatches, our success does go down.

So, you can look at success rates of 50 to 65%, down to potentially only 15 to 25%, because now you're not only dealing with the success related to making the myelofibrosis or the MPN go away, but what does the process of transplant bring in too? So, the answer to that can be very complicated. A lot of times, I think if we are looking at success of 50 or more percent at two or three years, that's usually a good indicator, because we know that without transplant the success is half to a quarter of that. And now we're talking about single percentages to maybe 10 or 12%, at best. If you're able to follow my statistics, there. My dirty statistics, so to speak.

Ruth Fein:
We actually only have time for, I think, one more question. There's a few more, but I think this is a really good one. Are stem cells tested so that we are sure that, I mean donor stem cells, so that we're sure that we're not transplanting diseased stem cells?

Dr. Faber:
So that's the advantage of using the donor. So, contaminating the graft or the stem cells, we eliminate that by not harvesting them from the patient and then giving them back. All donors undergo a pre-donor evaluation through the NMDP, also governed by the CIBMTR. So, there's a questionnaire that generally rules out 90 to 95% suspicion of having an underlying blood disorder. Normal donors are then seen at a transplant center like my own. We probably do 15 to 20 normal donor evaluations a year. There's a physical exam and a few more questions. We usually are able to tease out if there is something that the questionnaire hasn't identified. But after adequate evaluation, the risk of that should be approaching zero.

Ruth Fein:
Before we sign off, I'd like to end with a few words about how we change the conversation around MPNs, including myelofibrosis. And as we know, there's a lot of hope around myelofibrosis that wasn't there just a few years ago. And that's true for all MPNs and for their possible progression to MF. But Dr. Faber, would you leave us with how that translates to more hopeful conversations about stem cell transplants? What do you see as hopeful?

Dr. Faber:
Absolutely. So, when we talk about transplants, as I opened up the discussion, we as transplanters probably use things interchangeably. But now, our field is called cellular therapy. Because it's not only just donor stem cells. We have this process that we call CAR T, for example. We have biclonal antibodies. So really, it's more than just donor stem cells, I think, moving forward into the future. And that's what is most exciting because we're all looking for ways to control the disease but eliminate the bad side effects and the toxicities.

And BiTE therapy, CAR T, these are versions in my mind of almost mini transplants. Don't hold me to that, you can criticize that term, but I think of CAR T as a blend between auto transplant, where we use patient's own cells, and a donor. Without maybe the side effects. Now, we just have to figure out how to use that immunotherapy to have the same outcomes that we've had with transplant. And for some people that's curative intent. We're a ways away, but there are a lot of incredibly smart people and clinical trials out there, and so that's where the field is moving. At least from my opinion.

Ruth Fein:
I like your analogy. It's very hopeful and I thank you. So, thanks to our very special guest today, Dr. Edward Faber. To our audience, if you have new questions for your doctor based on our program today, be sure to make a note. If you're anything like me, it won't get remembered if you don't write it down. Also, don't hesitate to keep asking questions. So, we're usually our best advocates, which can improve our care and ultimately the quality of our lives. So, you can keep up to date with Patient Power on Facebook, and on Twitter and Instagram. That's also where you'll find many of our recent myelofibrosis information, our other webinars, and also about the next few and final programs in this series. That's all from here on this beautiful summer day in upstate New York. Take care, be well, and remember that knowledge can be the best medicine of all.

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