In this episode, we sit down with Lisa Stewart, a nurse practitioner with more than 25 years of transplant nursing experience, currently working at the post-transplant BMT clinic at the Dana-Farber Brigham Cancer Center in Boston. Lisa provides invaluable insights into managing chronic and acute graft-versus-host disease (GVHD) and shares her expertise, stories, and advice for patients and caregivers navigating post-transplant life.
Lisa describes her role in outpatient care, where the majority of her work focuses on managing chronic GVHD, a condition that is both a sign of a functioning immune system and a complex challenge. While mild GVHD can indicate that the transplant is effectively fighting diseases like leukemia or lymphoma, severe cases can lead to complications involving multiple organs. Lisa outlines the two major categories of GVHD: steroid-reactive and steroid-refractory, with the latter being particularly difficult to treat. Acute GVHD typically occurs within the first 100 days post-transplant and often impacts the skin, liver, or gut, whereas chronic GVHD can develop months or years later and affect a broader range of organs, including the eyes, mouth, lungs, and reproductive systems.
Clinical trials have led to significant advancements in treatment, including drugs like Ruxolitinib and Rezurock, offering hope to patients who fail first-line steroid therapy. Lisa also highlights Axatilimab, a newer medication discussed at the 2023 ASH meeting, although its availability remains limited due to manufacturing challenges. Despite these breakthroughs, steroids remain the frontline treatment, though they often cause challenging side effects like hyperglycemia, insomnia, and weight gain.
Lisa also emphasizes the critical role caregivers play in a patient’s recovery, managing complex medication regimens and providing vital emotional and physical support. She notes that without strong support at home, a transplant may not be feasible, particularly in the crucial first six months post-transplant.
The episode also touches on common post-transplant issues like oral GVHD, fatigue, and the importance of staying active. Lisa shares practical tips, such as using Dexamethasone rinses for oral GVHD and encouraging light activity to combat fatigue. She underscores the importance of early symptom reporting, especially for chronic GVHD, as prompt intervention can significantly improve outcomes.
Lisa concludes with a heartfelt story of a young patient who faced severe complications, including acute respiratory failure and paralysis, but ultimately made a remarkable recovery, even regaining mobility and starting a family. Stories like his, Lisa says, are what keep healthcare providers inspired despite the challenges.
We wrap up with a reminder about the resources available to patients and caregivers, encouraging early reporting of symptoms and proactive management. Lisa’s wisdom and dedication shine through, offering hope and practical guidance for those navigating the complex world of post-transplant care.
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Peggy Burkhard:
Hello, everyone. So, today, we have with us, Lisa Stewart, a nurse practitioner who works at a post-transplant BMT clinic since 2014 at Dana-Farber Brigham Cancer Center in Boston.
So, Lisa has been a transplant nurse for 25 years and sure knows plenty about chronic graft-versus-host disease, and will share her best tips, ideas, and inspiration with us today.
Hi, Lisa.
Lisa Stewart:
Hi, Peggy.
Peggy Burkhard:
So, we're going to have you share with us your role as a nurse practitioner.
Lisa Stewart:
I started working in an outpatient setting as a post BMT nurse practitioner at Dana-Farber in 2014. But prior to that, of course, I have years of just inpatient nursing experience.
So, as a nurse, you do not see nearly as much chronic GvHD because thankfully, most of them don't need to be hospitalized, therefore, we don't see that. But then outpatient, that's basically all we manage for post-transplant folks.
So, I always look at it as a double-edged sword, that sometimes you do need it in order to push the disease away, but then most of the time, it's more a nuisance than anything else that we need to deal with. But that's the reality of a post-transplant life.
Peggy Burkhard:
So, you say it's a double-edged sword, nobody wants it, but a little bit is good. Do you actually look forward to seeing a little bit of it?
Lisa Stewart:
In a way, yes, if we can control it, a little bit, but that's the problem. Once the floodgate is open, we don't really know where it's going to lead us. So, we always have like a formula saying that GvHD equals to GvL. This L is like leukemia or lymphoma or any kind of the tumor types that we deal with.
So, for some very aggressive diseases, we actually want to see a little bit of GvHD because that is the only tangible proof that we know that the new system is up and running and beating up the bad guys.
Peggy Burkhard:
Oh, good.
Lisa Stewart:
So, that's the good part. But then the problem is that sometimes when you open up the floodgate, it's not just one system – a second system gets involved, a third system gets involved, doesn't respond to steroids, doesn't respond to other things we throw at the patient.
I always remember the first thing I learned working as a transplant NP is the realization that of course, when patients have GvHD symptoms, your first mission is trying to curb the symptoms and make it possible for patient to go on.
But on the other hand, the more you add onto the immunosuppression, the less the patient is able to resist any infections because you're completely controlling the immune system. So, it becomes a very tough situation.
So, GvHD, whether it's chronic or acute, really has two huge categories. One is called steroid reactive, the other one is called steroid refractory. If we get to the point of steroid refractory, we're in a little bit of a problem.
Peggy Burkhard:
Okay, so let's talk about acute GvHD. We don't cover that as much as we cover chronic.
Lisa Stewart:
So, acute GvHD, the conventional wisdom is that it happens during the first one hundred days. However, now our categories are much more complicated. It really depends on the symptoms of which system is hit.
For instance, for skin, it doesn't matter when you get it, even if you get it three years down the road from transplant, if it involves a rash, that is always considered acute. Chronic skin GvHD really goes deeper into the skin layer, into the fascia and things like that.
But in the first hundred days, at least for the most part, there are only three systems that are involved. The first one is skin, most common, and then second one is liver. That is one of the reasons why we have to see our patients very frequently post-transplant because initially, patients will not feel anything different, but their liver enzymes will tell us. And in the acute liver GvHD almost always involves bilirubin. So, they're very soon are going to turn yellow and things like that.
The third system is really the toughest one, I think, is the gut. So, it's watery diarrhea. It doesn't matter how many Imodium or Lomotil you take, it wouldn't stop it. And a lot of times, it will be accompanied by severe cramping.
So, this kind of situation, patients usually have to be hospitalized. Why? Because you need to let the gut rest, therefore, they have to use TPN to support their lives; they can't be at home.
Peggy Burkhard:
So, Lisa, for those listening who don't know, what exactly is TPN?
Lisa Stewart:
TPN is total parenteral nutrition. That means that you are being fed through an IV access. The reason is that we have to let your gut rest, therefore, you cannot take in any food.
Peggy Burkhard:
Okay, thank you. Lisa, I want to ask you about clinical trials. There's just been so much success, especially the last six years – drugs, new drugs on the horizon, and I know a lot of it is because of the clinical trials that took place. Just share how you feel about that.
Lisa Stewart:
Yes, definitely. I mean, post-transplant clinical trials to deal with GvHD is our number one priority. And then in the last few years, we have two new drugs. One is Ruxolitinib that can treat both acute and chronic, or Rezurock that only is approved for chronic.
However, the prerequisite is that patient has to fail steroids. So, the first line of defense, no matter if it’s acute or chronic, is always steroids, meaning Prednisone in most cases.
Peggy Burkhard:
But you do see so many new drugs finding their way. And I mean when we talk to patients, there just seems to be so much excitement that there are other options now.
Lisa Stewart:
Yes. And in 2023, the ASH meeting, they all talk about Axatilimab. That is approved, but right now, it's because of manufacturing issues it hasn't been available to us. That's also another newer drug to treat GvHD.
Peggy Burkhard:
Okay. So, let's talk about the most common medications used at this point.
Lisa Stewart:
So, we always start with steroids. So, the Prednisone. The problem with Prednisone as most patients will know, is that not many people can really tolerate it well. Inevitably, it will lead to hyperglycemia, that's number one. It's tough on the stomach and most patients end up with some form of gastritis, and also because it's an upper, patient will have trouble sleeping. And then another thing is weight gain. Significant weight gain is also tough for patients to deal with.
So, for acute GvHD, the formula is usually we do it two milligram per kg. However, we usually don't go that high because if you are weighing a hundred kilos, about 200 pounds, that means that we give you 200 milligrams of Prednisone a day. That is huge. However, sometimes we have no choice but doing that.
Peggy Burkhard:
Okay, yeah. We hear that all the time, the love-hate with steroids.
So, Lisa, let's talk about chronic GvHD and the most common organs it affects.
Lisa Stewart:
For chronic GvHD, it's about the same as acute, that most common is still skin. However, because it's a little bit down the road from transplant date, the rash usually doesn't come out as gangbusters. It's a little bit more controlled, mild.
So, we almost always start with steroids too, but we usually use one milligram per kilogram, sometimes even half a milligram per kilogram. So, it's a lot less Prednisone. Then we'll see if the patient responds.
But then because at the chronic stage, basically most of the organs are game for GvHD. You can develop ocular GvHD, you can develop mouth, oral GvHD. It can go down the system, it can definitely hit your lungs, it can hit your kidneys, and it can hit … for women, it will be the vaginal GvHD. So, many, many parts of your organs can be involved.
Peggy Burkhard:
Yep, that's what we hear. So, we're going to talk about caregivers for a minute, the wonderful heroes of all of this.
Lisa Stewart:
Yeah, they're usually the unsung heroes, right.
Peggy Burkhard:
So, why don't you give us some of your best tips regarding caregivers?
Lisa Stewart:
So, because people who come to transplant usually are in their late fifties or (up to) late seventies, so their spouses will take on this incredible task of managing the medications and the nutrition, and the fluid intake. And sometimes, it can create some tension between the two. Because we are all adults, certainly nobody wants to be told what to do at what time.
However, these unsung heroes really do their best to keep on reminding their loved ones times to take medication, time to drink fluid, time to eat more protein. So, their role is actually pivotal in a person's recovery.
Sometimes we even talk to the doctors, if a person doesn't have a very good support at home, we probably shouldn't venture into the land of transplant because particularly, during the first six months or so, it is critical to have somebody there for the patients.
Peggy Burkhard:
And vigilant.
Lisa Stewart:
Very vigilant, yeah.
Peggy Burkhard:
On the watch all the time, making sure … little things can make a big difference. Correct?
Lisa Stewart:
Absolutely. Even just managing the medications, I have calculated if you walk into transplant without taking any meds at all, by the time you walk out of the hospital during the first couple of months, you would be taking 24 to 27 pills. And usually, they come with very strange names, and we usually have two names for everything. So, for a spouse to manage that, that's nothing short of being heroic, right?
Peggy Burkhard:
Yeah. Let's talk about oral GvHD, maybe all of a sudden, an aversion to spicy food, that kind of thing. Do you see that often?
Lisa Stewart:
Yes. That's one of the very common GvHDs. Okay, relative to cancer, oral GvHD is “not that big a deal,” but it is because you're living with it 24/7. It is really, really difficult to maintain your nutritional status when you cannot eat anything.
Most oral GvHD is usually starting with a very dry mouth. So, a side note, when you have dry mouth, you really have to worry about your health of your teeth because that can really lead to cavities. So, a lot of the patients say, “I had no cavities all through my adult life, and now I have several cavities.” I mean, coupled with steroids, that really is detrimental. So, people really need to take very good care of their teeth when they have oral GvHD.
And then oral GvHD a lot of times starts out with dry mouth and then sensitivity to the spices or sensitivity to the temperature of foods, and then lateral ulcers, ulcerations that can be horrendous. But usually, oral GvHD does respond to topical treatment like a Dexamethasone rinse. So, that can really calm down the inflammation.
Peggy Burkhard:
Oh, thank you for that. So, let's tackle fatigue, everyone's number one complaint, right?
Lisa Stewart:
Yes. That's the number one complaint. It's not just with transplant folks, it's really with any kind of cancer patient who undergoes cancer treatment. That is across the board our number one complaint, because the problem is that it's very difficult to deal with it. So, the fatigue is also very subjective.
So, there were many, many nursing studies done on the fatigue issue, and then the conclusion seemed to be saying that you really have to keep on moving, it's counterintuitive. That's the only way that can get you to feel a little bit better.
Also, I have to say, I don't know about other centers, but Dana-Farber is very, very strict with the activities of our patients, and so you can't really do anything that you want. This is particularly hard for younger patients because they can't do anything; socializing and things like that with their friends.
So, when they are home, they cannot do anything, then they really feel tired all the time because boredom is really another source for fatigue.
Peggy Burkhard:
And they're not being energized.
Lisa Stewart:
Right, right, exactly. And then also all the diagnosis and the treatment are still so fresh in their minds, so that's an intimidating factor for them to do anything too.
Peggy Burkhard:
Yeah, I like your message to keep moving, I think that's just such an important one. Even if it's just a little bit.
Lisa Stewart:
Even just very small things, folding some laundry, and then loading the dishwasher or little things. If people have a hobby, some painting or something like that – just something to break up the monotony in daily life.
Peggy Burkhard:
I know you've been doing this for a long time, and I am sure you have so many stories, but could you share a patient experience with us today?
Lisa Stewart:
Oh yes. He actually … because Dana-Farber is affiliated with the Red Sox and things like that, he was invited to talk at one of the fundraisers too. He's a young man in his early thirties and then diagnosed with acute leukemia. Actually, he participated in one of our clinical trials to prevent GvHD, but obviously, it didn't quite work.
Anyway, so he was sailing through the program until about nine months out. He got COVID first, but then he quickly overcame COVID. He looked really good. But then about a week after he recovered from COVID, he actually developed acute respiratory symptoms, and he had to be hospitalized.
Not only just hospitalized, he actually was intubated and he was on the breathing machine for a very long time. In the meanwhile, many things happened. His blood pressure had dropped and that it looked like he was septic. So, we did a million-dollar workup, and then from the beginning to the end, nobody really knew what happened.
And we threw it up to post-viral syndrome. And then just as we thought that finally he was turning the corner, we started him on steroids, his liver variance line began to shoot up. At that point, we really weren't sure if it's graft-versus-host or if it’s something else.
We did a liver biopsy; it proved to be graft-versus-host disease. And then because he was intubated for so long, actually, by the time he left the hospital for a very active young man, he turned into a paraplegic. He couldn't use his arms, and then he was sent to rehab.
We really don't know if he's going to make a full recovery, but about a year later, right now, he's fully recovered.
Peggy Burkhard:
Oh, good.
Lisa Stewart:
After everything, we thought it was impossible. He regained the use of his hands and arms, although his left arm was still a little bit weaker than the right arm, and he also got married in the meanwhile. Now, he's ready to have children with his wife.
So, that is an incredibly inspiring story, that he can overcome that much. Usually, our patients don't even get nearly this sick, but he did. But then he came through.
Peggy Burkhard:
Oh, Lisa, I'm so inspired right now. This is a great ending.
Lisa Stewart:
Stories like this really keep us going, the providers. Inevitably, there are stories of the opposite, but these stories really keep us going.
Peggy Burkhard:
Yeah. Well, Lisa, you have been doing this for such a long time. When you think of all the people out there that just need your expertise, is there anything else you want to cover today? Any parting pearls of wisdom?
Lisa Stewart:
So, with particular chronic GvHD – acute GvHD, because it's not subtle, so it's very difficult for patients to ignore it, the symptoms. But for chronic GvHD particularly, like a little bit of eyesight change, you just feel that something is stuck in your eye all the time, or in the morning, you woke up with crust over your eyes, a lot of people would think that this is probably nothing, and they wouldn't relate that to GvHD, but they actually are the first symptoms for ocular GvHD.
So, early reporting, no matter how trivial you think that is, is incredibly important. Just like everything else, the sooner we can go in and start doing the interventions, the better the outcome.
Peggy Burkhard:
Oh, I love that. We have resources for your patients. I hope that you know about the many resources that are out there because we just want to help you help them get through this. So, please let us know if there's anything we can help you with.
And I just want to thank you again today for sharing your heart and your wisdom with us. It's appreciated.
Lisa Stewart:
And thank you for giving me this opportunity to talk. I really appreciate it too.
Peggy Burkhard:
Well, thank you. So nice to meet you, Lisa.
Lisa Stewart:
So nice to meet you too.