Chronic Graft-versus-Host Disease of the Gastrointestinal Tract and Liver

Learn how GVHD can affect the gastrointestinal tract and liver following a transplant with donor cells, and strategies available manage it.

Presenter: Jeanne Palmer MD, Mayo Clinic Arizona

40 minute presentation, followed by 20 minute Q&A session.


Chronic graft-versus-host disease (GVHD) in the gut and GI tract is a common complication of a transplant using donor cells. Chronic GVHD can also affect the liver and, rarely, the pancreas. Patience is needed as it may take a long time for symptoms of GVHD in the gut to resolve.


  • Chronic GVHD in the GI tract is common, and often first occurs when a patient is tapering off steroids
  • Other causes of GI problems such as infection, medications and gastroesophogeal reflux should be ruled out before making a diagnosis of chronic GVHD of the GI tract
  • It’s important to report symptoms of chronic GVHD to your doctor promptly; early treatment can help reduce the severity of the disease

Key Points:

03:21  Symptoms of chronic GVHD in the gastrointestinal tract

17:13  Steroids are the standard treatment for chronic GVHD in the GI tract

17:51  Side effects of steroids

19:57  Chronic GVHD in the GI tract often starts when a patient is tapering off steroids. 

23:03  A clostridium difficile (C-diff) infection, and some viral infections can cause symptoms similar to chronic graft-versus-host disease (GVHD) in the gut.  

24:18  Medications such ursodiol and mycophenolate mofetil (CellCept®), should be ruled out as the  cause diarrhea before diagnosing chronic GVHD in the gut.

25:18  Chronic GVHD of the liver: symptoms and treatment.

29:47  Treatment options if chronic GVHD does not respond to steroids (steroid refractory GVHD)

31:16  Chronic GVHD of the pancreas: symptoms and treatment.

35:21  Managing the symptoms of chronic GVHD with anti-nausea pills, small frequent meals, nutritional supplements, Sea-Bands®, ginger, probiotics and fecal transplants.

This recording was made possible, in part, by support from Pharmacyclics and Janssen, Incyte Corporation and the Meredith A. Cowden Foundation.

Transcript of Presentation

00:00  Introduction:  Hello everyone. Good morning. So good to see you all here. It's always a pleasure to come and talk at these conferences; and an honor to be able to do so.

So, I'm going to talk about graft-versus-host disease of the GI tract and liver. I think it's important to first note, this is a nebulous area, because when you think of true chronic graft-versus-host disease, there [are] very few findings you have in the liver. That being said, chronic graft-versus-host disease of the GI tract is very bothersome to people, and this can be even up to a year or two after transplant.  So this certainly is something that's not just limited to the acute GVHD setting that we think of, which is up to day 100.

So many of the things that I'm going to talk about when I talk about acute [she means chronic] GVHD of the GI system and the liver are going to be things that are very similar to acute GVHD, primarily because we think the pathology of it is quite similar. I will, however, point out where some of the differences are, and what is really considered to be chronic GVHD of the GI system as well.

01:05  Overview of Talk:  So what I'll try to talk about today, is what is graft-versus-host disease? And I'm sure, since it is Sunday, and the conference is drawing to a close, you guys have heard lots about what chronic GVHD is, so I'm not going to go too much into the background of that. What are the symptoms? What tests are needed and what is the treatment? Because obviously, the treatment is what you really want to know about.

01:28   Difference between chronic GVHD and late onset acute GVHD:  So if you talk to some of us, we get a little bit particular about what's truly acute and what's truly chronic. It doesn't matter as much in terms of treating somebody, but it makes a big difference when we're trying to understand the pathology behind it, and for research studies. So if somebody has graft-versus-host disease symptoms involving the GI tract, which I'll go over these later as we go on, then I'd look at a person in two ways. Number one, if you're before day 100, you have classic acute. And then if you have symptoms of chronic graft-versus-host disease elsewhere, everything's really considered chronic, but if you don't have any symptoms of chronic GVHD elsewhere, it's considered more late onset acute.

So, if you're looking at… sometimes you get to look at the doctor's notes about you, you might see the term ‘late onset acute GVHD,’ and that's because if you don't have any other signs of chronic, then we do consider it more of a late onset acute. Again, it's not going to matter as much about how they treat you, but if you're reading a doctor's note, you might say ‘Well geez, I'm nine months out from transplant. Why does this say late onset acute GVHD?’ And that's the reason why. And so the definitions matter in some respect when thinking about it.

02:51  Graft-versus-leukemia or graft-versus-lymphoma effect:  So as you know, the reason that we have graft-versus-host disease is because we also want graft-versus-leukemia disease, or lymphoma or infection or whatever. So basically, we want the immune system to behave in the way we want it to, but we can't quite separate that from the immune system behaving the way we don't want it to, which is graft-versus-host disease. And this is the way to think about it, is you have this balance. Unfortunately you can't have one without the other. People have been trying for the last 20 years to figure out ways to do that and it's tricky.

03:21  Symptoms of chronic graft-versus-host disease (GVHD) in the gastrointestinal tract (GI tract):  So what are some symptoms that people will have when they develop some type of graft-versus-host disease of the GI system? Nausea, vomiting can be symptoms, diarrhea, abdominal pain, bloating and cramping in the stomach area, difficulty swallowing. Sometimes people will get the sensation of food getting stuck in their chest. There could be pain on swallowing. Sometimes there's no symptoms at all, but somebody will say ‘oh, your eyes look a little bit more yellowed.’ Weight loss and also malabsorption.

03:53  Picture and description of gastrointestinal (GI) tractSo the areas we will discuss today... this is just a way of looking over the GI system.

This is your liver right here, and that's the gallbladder. A lot of people have that one taken out. This is your pancreas right back here, all these little narrow things that look like a worm are the small intestines, and there are feet upon feet upon feet of small intestines. And then this area that's pouched here, that goes up and around is a large intestine. This is the stomach. I probably should have done that first. And then this is the esophagus going up. And these are the areas that can all be affected with graft-versus-host disease in the abdomen.

So whenever I give talks, whether it be to patients, or whether it be to other physicians, I always like to use case studies, because then it brings it down to what we're thinking about, rather than some abstract concept.

04:56  Chronic graft-versus-host disease (GVHD) can cause difficulty swallowing:  Of course, these are all  made up patients, so they aren't going to reflect anybody, and no HIPAA violations or anything here. A 32-year-old patient, one year out from transplant, who starts to notice some difficulty swallowing. He comes in with complaints of ‘Oh, the food feels like it's really getting stuck in my chest.’ But he has no problems swallowing liquids or soft foods.

So, when I see that, I think of a few things. First of all, I think ‘Well geez, sometimes what happens is people have chronic GVHD of the mouth, which you either will hear from or have heard from Dr. Treister, and that is where you can have a lot of dryness and difficulty getting saliva, so it's really hard for things like bread and stuff to swallow.

05:44  Doctors use endoscopy to look at esophagus and stomach:  However, we also have to consider what can be going on in the esophagus itself. The best way to evaluate this is to take a look, and so what that involves is an endoscopy. So, this is a picture of an endoscope. It looks pretty harmless here. What they do is, see the doctor looks through this eye. This is attached to something, and then this is a tube that goes down in the esophagus and into the stomach. When they go in through the mouth into the stomach, you can get partway into the small intestine. So, it's a very good way of looking at both the esophagus, the stomach and the small intestines. So, generally speaking, when the doctor does that, they're looking at all of these areas.

However, the other way that they use endoscopies is to look in the large intestines, and then they go up the rectum; and I'll go into that when we talk about lower GI stuff, but they can go into the rectum and make it, if they really want to, all the way to the tail end of the small intestine. It's very hard to get into the center of the small intestines. There are ways to do this—like capsule studies and stuff like that—but they aren't as useful for evaluating things like graft-versus-host disease. They're more useful for things like chronic GI bleeds, if someone has iron deficiency anemia and you can't figure out where they're losing blood.

But most of the action that will happen, or that we can look at, will happen in the upper part going to the small intestine, that we can get an idea of the small intestines, or else in the lower part. That being said, graft-versus-host disease can still affect the small intestine; it just becomes a lot trickier for us to identify and diagnose. And usually it doesn't just happen in the small intestines. Usually, the whole GI tract can be involved.

07:25  Picture of upper endoscopy:  So the upper endoscopy, and this is just a little picture of it, basically they go down through the mouth, down the throat and look into the stomach. And, again, they can get to some of the small intestines here as well. And first what they do is look at the esophagus. Now, sometimes this can give us very useful information. You can see that there might be strictures in it, or narrowing, which I'll show you on an x-ray, that is coming up. They also might see irritation in it, and changing of the tissue that you can see with infection.  So different infections can affect the esophagus and the stomach. But sometimes it can appear normal, but still be affected.

The stomach is the same. You can see irritation. Sometimes people have peptic ulcer disease. Sometimes symptoms we think can be graft-versus-host disease are something entirely different, which is why we really need to evaluate them rather than just saying ‘Oh, this is GVH,’ and just throw some steroids on. So, we really need to make sure what we're looking at is what's going on.

08:24  Why do a biopsy to diagnosis graft-versus-host disease (GVHD)?  However, even if everything looks completely normal when they take a look, a biopsy needs to be taken, because sometimes the biopsy will demonstrate graft-versus-host disease, and this could be very helpful in explaining symptoms that people have, and helpful in guiding our treatment as well.

08:41  Picture of blockage in the esophagus, stricturesSo this isn't a perfect picture. This is a Schatzki ring. This is a picture I took of a patient, and basically you see here, there's narrowing. So, the white is barium—sometimes they'll have you do a barium swallow when they're trying to evaluate different narrowing areas—and then if you see a change ... basically, barium is white, like this. This is the esophagus going into the stomach. You might see strictures or narrowing, and this is, by this little band right here, where you see the barium isn't just going down like a tube. It gets stuck because there's a blockage in there.

And when they see that, if you see it more in the upper or middle third of the esophagus, so basically going down to about here, when you see a stricture in that area, that's one of the few diagnostic criteria for chronic GVHD, that is, involving the GI tract. There's not very many of them. That being said, you can still have the late onset acute GVHD which can be just as bothersome, if not more so.

09:42   How blockages in the esophagus are opened:  So if they find an esophageal web, they can sometimes dilate it. So, they go in with that small tube and they have a balloon on it, and they pump the balloon up, and that stretches everything out to allow food to go down. Sometimes that needs to be done even two are three times for it to be fully effective.

10:00   Esophagus not moving well can cause food to stick in throat:  Other findings of chronic GVHD that are more specific, and these aren't diagnostic, they're just findings that we'll see. Sometimes the esophagus doesn't move as well as it should. What can happen is there's a lot of connective tissue in the esophagus. And just as in the skin, you can get skin thickening and tightness of the joints, the same thing can occur in the esophagus. So, it almost becomes a tube-like structure. In its true sense, the esophagus should push the food right down. There's muscle that exists in the esophagus that helps push the food down, and that muscle continues through the whole GI system, pushing, pushing, pushing to get the food down through everything, so eventually you're evacuating it when it's been fully ... all the nutrients have been taken out of it.

So sometimes the esophagus doesn't move as well as it should, and that can also cause the food sticking in people's throat. This is generally due to the scar tissue developing in the esophagus, just like you get scar tissue, the thickening of your skin, thickening of the joints, which also is like scar tissue.

11:03  Gastroesophageal reflux disease, hiatal hernias, and infection can also cause problems with swallowing:  So let's talk about other things that can cause these symptoms, because that's important to know, too. If you have these symptoms, it doesn't always mean you have graft-versus-host disease. Gastroesophageal reflux disease, which is a very common thing to happen, happens a lot, especially if someone's on steroids for any length of time. You can get gastroesophageal reflux disease, or sometimes even peptic ulcers.

Hiatal hernias can cause that. A hiatal hernia is where part of the stomach goes up above the diaphragm, and so basically where the stomach produces all that acid. And if the diaphragm usually protects it, because the diaphragm blocks the esophagus from the rest of the stomach, but if part of the stomach is up above the diaphragm, there's no blocking it from going up into the esophagus, and that can cause a lot of pain and discomfort.

Also, infections can cause this. Yeast infections. So sometimes you'll look down and you'll see... and some people, I'm sure have experienced thrush, where they get that white, I don't know, cottage cheese, or ... it doesn't look quite like cottage cheese., anyway, white yucky stuff in the mouth. That can occur all the way up and down the esophagus.

It can also be viral. Viruses like cytomegalovirus, herpes simplex virus. Those are the two major ones we see, but viruses can affect the esophagus, and sometimes you'll see a very atypical appearing esophagus, and you'll biopsy it, and they'll say, ‘this doesn't really look as much like graft-versus-host disease.’ You'll start to see viral inclusion bodies, which are very characteristic findings on a slide that you look at under a microscope that can really give us information in terms of what's going on. And sometimes they can coexist. I had a patient who went and did an endoscopy. The biopsy showed some graft-versus-host disease, but also showed what looked like HSV, so we treated both of them, and eventually the symptoms really got a lot better.

12:52  Small intestine bacterial overgrowth can cause swallowing difficulties:  Another things that can cause these symptoms is small intestine bacterial overgrowth. This is a very common thing to have happen to anybody, not just people who have had a transplant. And what it is, is after all sorts of antibiotics, you get the bad bacteria growing and they overgrow so that it prevents food from being digested appropriately. It used to be that you needed an endoscopy to do the test because they would do an aspirate, and they would grow it out and culture [it], and you had to have so many bacteria grown to be able to diagnose it. But now they can diagnose it with a breath test, and sometimes you can treat it with a few weeks of antibiotics, oddly enough, even though antibiotics are the cause of it.

13:32  When muscles in throat don’t function well, food can stick in throatAnd then finally, as I talked about, the impaired GI motility, and that's again where you develop - the muscles in the esophagus [and] the stomach, don't function like they should. Again, they are really there to pump the food down, and keep it moving along so it can get to where it needs to go. If those muscles don't work, food gets stuck. Sometimes it gets stuck in the esophagus, sometimes it even gets stuck in the stomach.

13:58  Treatment options for chronic graft-versus-host disease (GVHD) of the GI system:  So these are all very important things to evaluate before you just say ‘Oh yeah, this is GVHD. Let's throw some steroids on it.’ Or immunosuppression drugs.  I'm going to talk about the treatment for all the graft-versus-host disease of the GI tract together, so I'm just going to go through the different ones in the intestines before I go into treatment.

14:20  Evaluating a patient with cramps, diarrhea and dry mouth:  So let's take patient number two: Jeffrey, 44 year old gentleman, nine months after a bone marrow transplant. He develops stomach cramping and diarrhea. He also has some dry mouth and some findings consistent with chronic GVHD.

So in this case we'd probably do both an upper and a lower [endoscopy], but a lower endoscopy is really helpful in making the diagnosis, especially when there's a lot of diarrhea. And what that does, is that goes up through the large intestine all the way up through the colon, and down here. And this is where the large intestine meets the small intestine. And you can sometimes go just into this part of the small intestine to get biopsies as well. Unfortunately, when you have to have one of these, the preparation is really tough, especially if they do a full colonoscopy. Sometimes you'll just do a sigmoidoscopy, which goes about up to here, which I think is generally what we start with, unless there's really something ... like unless you do that, and it looks normal, and then you do a CT scan or an x-ray or something that show inflammation in this part of the intestine down here, in which case we need to do the full scope.

But if you have to have the full colonoscopy, the prep is really difficult. I'm sure many people in this room have had it. You have to drink a lot of fluid, you're going to the bathroom all night long if you're having it done in the morning. It's a very, very unpleasant experience. That being said, it's really important, because if you don't cleanse out the colon, there's no point in taking a look up there because all you're going to see is stool. You're not going to see anything that's going to help you. So although the prep is very, very tough and difficult to go through, it's a very important part of it.

Now, everything may look normal. Your doctor may take a look and say ‘Oh look, everything looks okay.’ It's very important to get biopsies, again, because the biopsies sometimes will give us information that just taking a look at what the surface looks like will not be able to give us. And again, that may look completely normal, but the biopsy is important.

16:18  Have your local gastroenterologist consult with the transplant center:  Now, the other thing is, that a lot of people don't continue to get care at this point at the transplant center. They go home and have a general gastroenterologist do these, and that is fine, but it's very important if you have biopsies done, to have them reviewed at a center that sees graft-versus-host disease. Because if you take pathologists—and it's nothing against the pathologists who are out in the community—they just don't see graft-versus-host disease, so they're not going to be able to recognize it, rate it appropriately, be able to discern what's more graft-versus-host disease, what's more viral infection.

So even if you have a biopsy done, say, in Idaho, then you want to make sure it's reviewed at your transplant center as well; because sometimes the outside pathologists are spot on, they've been trained in a place where transplants are done. But sometimes they haven't, in which case they're not going to be able to recognize and decipher some of the more nuanced areas of graft-versus-host disease.

17:13  Standard treatment for chronic graft-versus-host disease (GVHD) in the GI tract is steroids.  So, what is a treatment for anything in the GI tract? Pretty much our standard approach, generally involves some type of corticosteroids. So, there are steroids that are not absorbed into the body that well. Topical steroids, such as budesonide and beclomethasone. Beclomethasone often comes in a corn oil, which sounds gross, but I'm surprised how many people tolerate it really well. That's more for the upper GI tract. The budesonide, the general formulation, is that is an enteric coated one, which is good because it can make it down to the large intestines and then start releasing the steroids down there.

17:51  Side effect of taking corticosteroids for chronic graft-versus-host disease (GVHD) in the GI tract:  Even though they're considered non-absorbable, some absorption occurs. So, when people are taking these, they often will have some of the side effect of taking corticosteroids, like difficulty controlling blood sugars, and long term, it can affect bones, make you have weakness in the muscles, make the face shape a little bit differently. There are absorbable steroids that are known to be absorbed such as prednisone, and I'm sure that's a steroid that many people in this room have been introduced to, and that is our stand-by. Prednisone can be a pill, it can also be given as Solu-Medrol®, or prednisolone, which can be given intravenously.

18:35  If chronic graft-versus-host disease (GVHD) is severe, a patient may be hospitalized to rest the gutIf the graft-versus-host disease is severe, and generally what I do is if somebody is not able to eat, having severe symptoms, I'll generally admit them to the hospital, because the best thing to do for the gut is to give it a break while you let it try to heal. Because if you think about it, the way I envision this is, let's say that you get road rash on your arm. You fall off of your bicycle, or you trip and fall and your whole arm gets scraped up. You know, they're really painful when you get them. And when your arm gets scraped up, first of all, you don't want to have all sorts of stuff rubbing against it because that'll hurt, so you want to give it a break. And the second thing is, it takes a long time to heal because it needs to form the new tissue, then scar tissue and everything else.

So, the gut takes a long time to heal. So, if it's really damaged, you need to give it a break for a while and not eat anything. And then in some cases we'll even feed people through an intravenous line. If somebody's not having that much trouble and maybe just having some nausea, more upper GI symptoms, a lot of times I still try to treat it as an outpatient.

So again, it really varies, and that's something that each doctor will determine as they see you and look at you, and look at blood work, and it's a general picture that decides how aggressive we need to be: inpatient versus outpatient, whether you need to go on complete bowel rest or just  limit your diet to more bland foods.

19:57  Chronic graft-versus-host disease (GVHD) in the GI tract often starts when a patient is tapering off steroids.  As well as starting steroids, if you're still on immunosuppression medication you can continue that, such as tacrolimus, cyclosporine, sirolimus. And then sometimes you will have to restart them. So, if you're completely off immunosuppression medications, then you get them restarted.

The one thing also to remember is after day 100 you go home, your doctor's there, you go see maybe a transplant doctor and they say ‘Okay, well I want you to taper off your tacrolimus, or cyclosporine, or sirolimus.’ This is a time when you get this. This is a time when a lot of that occurs. And so, it's really something that I always tell people to be very aware of as they are tapering off their immunosuppression, is that's often the time when we see graft-versus-host disease.

20:42  It’s important to promptly report symptoms of chronic graft-versus-host disease in the GI tract, such as diarrhea.  And it's tough, because then they're many times away from us, and hard to really get a hold of and to be able to manage. But if you are in the situation where you're tapering off your immunosuppression medication and start to get symptoms, it's very, very important to address them quickly. Don't think ‘Oh, I have a little diarrhea, oh this probably is a virus or food poisoning or something.’ It's something that you really want to stay on top of because it's very important to be very prompt on dealing with this, or else you're sicker for a longer period of time, and have problems for a longer period of time.

Ideally, when you start steroids, your symptoms should go away pretty quickly. Especially if you have diarrhea and you stop eating and you get steroids, your symptoms should improve. Now, sometimes they don't. Sometimes it takes a while for the gut to heal. Again, this is the reason why it's so important to bring up these things quickly. Because if you could stop eating and get steroids on board, or even just get steroids on board, sometimes you can stem it, you can nip it at the bud so it doesn't get really severe.

21:45  It can take a long time for the effects of chronic graft-versus-host disease (GVHD) in the gut to heal.  Once it gets really severe, it's a lot harder to get back to being normal. So even in some cases, your diarrhea might get better, but it could take a while to heal, and we'll go back to that road rash on the arm. Think of how long it takes for that to get better and the skin to get normalized and everything else. It takes a while, because you have a lot of tissue that's damaged. So, the same thing occurs in the gut. You have to be patient and gentle with it.

It's one of those things that's extremely frustrating for both patients and doctors, because you're still having symptoms. We then never know[whether] to keep pounding you will steroids or try to pull back on them. And then, we also don't know whether the diarrhea is because you're getting used to re-feeding yourself, especially in the cases where you aren't eating, or if this is something that's persistent graft-versus-host disease.

22:35  Be careful about eating dairy while recovering from chronic graft-versus-host disease (GVHD) in the gut.  Other things are, like, dairy intolerance is very common after this. Even if you think of getting a common stomach virus, a lot of times it takes a couple days to get dairy food back in because of the fact that there's a lot of bacteria in your gut that produce enzymes that digest the lactase in the milk, and ice cream and stuff. So, you need to make sure that you're very careful about dairy, in particular, because of the fact that you're going to be missing a lot of those bacteria that are important.

23:03  A clostridium difficile (C-diff) infection, and some viral infections can cause symptoms similar to chronic graft-versus-host disease (GVHD) in the gut.   So what else could this be? It's really important also to rule out infections. The first test that should always be looked at is something like C-diff, which is incredibly common in patients who have spent a lot of time in the hospital. This is a bacteria clostridium difficile. Now, most of us have the bacteria. If you grew out all the bacteria in our gut, you'd find clostridium difficile. But sometimes what happens is that it gets really nasty and starts forming a toxin, and the toxin gives you really severe diarrhea. C-diff is much more common after you've taken antibiotics, and all transplanters know, we're very, very open with antibiotics. We give them all the time, basically. So, a lot of people really will have ultra gut flora. So antibiotic use kills off the good bacteria and allows things like C-diff to grow.

Other things are viral infections. So, these aren't as easy to diagnose, because the tests that you often do to run them may take up to a week or so to come back. But also, norovirus, rotavirus, things like that. Often, you'll hear about ‘Oh, the kids in this ... your child's going to school, all the kids are getting diarrhea.’ That's usually one of those viral infections that gets passed on, especially in elementary school where kids are still learning how to wash their hands appropriately and stuff.

24:18  Medications, such ursodiol and mycophenolate mofetil (CellCept®), should be ruled out as the  cause diarrhea before diagnosing chronic graft-versus-host disease (GVHD). The other thing that can cause diarrhea is medications. A lot of antibiotics can cause diarrhea. Even some of the medications, like ursodiol, that you'll take for the liver can cause diarrhea. And the other thing is, ione of the immunosuppression drugs, mycophenolate, or CellCept®, can cause diarrhea, and can cause some pathologic symptoms very similar to graft-versus-host disease. And which is why it's very important to stay in close touch with your transplant physician, because these are things that your community hematologist/oncologist will probably not be aware of.

Now granted, it doesn't mean if you're having diarrhea, stop your CellCept®; but it's definitely one of those things just to be aware of, because sometimes it may mean that if you're on CellCept®, it may not be that you have graft-versus-host disease, it may be the CellCept®. And sometimes we can use different formulations of it that are better tolerated by the gut. Or sometimes we switch to another medication because that's a really bad side effect of CellCept® that we want to try to deal with.

25:18  Chronic graft-versus-host disease (GVHD) of the liver:  All right. So, we're going to move on. So, we're going to take patient number three, Maria. A 52-yearold female, nine months out from an allogeneic stem cell transplant. She's at home and starts to notice some yellowing of her eyes. Her family members say ‘You know, something doesn't look quite right there.’ She goes to her doctor, the blood work shows abnormal liver tests.

 So liver GVHD is a tricky one, because it's not always something that you feel. And generally speaking, in the first 100 days after transplant, I usually see liver along with something else. So, you'll have liver and GI or liver and skin. So, you're never wondering what's going on in the liver, but after transplant, sometimes I'll see this liver GVHD just cropping up on its very own. But ,generally speaking, it's not something that a person will feel. So, so they'll come in and be totally fine, and be like ‘Why are my eyes yellow?’ It's something that your doctor may find on a blood test, so it's really important to keep getting the blood tests regularly, even if you say ‘Well, they're always normal. Why are you making me go get my blood drawn again?’ It's because it can diagnose things like this.

Now, the eye yellowing is something that occurs when it's progressed pretty far. That's when your bilirubin has to be at least about three. Normally, bilirubin upper limits [are] usually around one. So, it can even be up to two and you might not notice any differences. Sometimes also the urine will look really dark. These are a couple things you can see when your bilirubin goes up. Sometimes with liver GVHD, it's not the bilirubin that goes up, but other liver enzymes like the AST, the ALT, alkaline phosphatase, stuff like that.

26:54  Rule out infection and drug induced liver damaged before diagnosing chronic graft-versus-host disease (GVHD) of the liver. So, diagnosis of liver GVHD is tricky. There are a lot of things that can make your liver enzymes go up. I tell people ‘You sneeze the wrong way, your liver enzymes will go up.’ If somebody goes out binge drinking, their liver enzymes will go up, even if they're completely healthy. So, it's important to differentiate GVHD from other issues as well as infectious issues. Of course, there's the common things: hepatitis B, hepatitis C, even hepatitis A that can occur.

I have to say, we always look for all of these, but I've never found them in a transplant patient. Now, I say that, and of course, in the next few weeks I'll find it, just to prove me wrong, but you always have to rule out the infectious issues. That can generally be done by a blood test. But then you also have to rule out other things like medications. Drug induced liver injuries are a very common thing.

The biopsies are not perfect, but they do often help us differentiate graft-versus-host disease from drug induced liver injury or something else. And it's important to look at that, because again, if you're taking a medication that's making your liver go unhappy and I start pounding you with steroids, I'm not doing you any favors. I've got to figure [that out] and try to take off a medication.

28:04  Chronic graft-versus-host disease of the liver is treated with predinisone, restarting other immunosuppressive drugs and/or ursodisol.  So, if you do indeed have liver GVHD, prednisone of course, it's our go-to drug. Continuing or restarting of immunosuppression drugs like CellCept®, sirolimus, tacrolimus, cyclosporine, and, oftentimes, we'll use ursodiol. Now ursodiol is a pill that just helps sequester and bind bile acids. I'm still trying to figure out why it's so good for the liver, but almost anyone who has abnormal liver tests, if I give them ursodiol it will help a little bit.

And we, one of the first things I'll sometimes do if I see elevated liver enzymes is say ‘Let's try some ursodiol before we get too excited and start biopsying stuff’’ Again, every doctor practices differently—and so anything that I'm saying it is a generalized thing, and not something that you should go [and say] ‘Oh wait, this woman [who] is talking to me said to use this drug,’ because every situation is a little bit different. But sometimes ursodiol is added. It's not a fun pill to take. It's big. There's a liquid form of it, but it tastes really awful. So it's not a great pill to take, but it can really help. I think it can certainly tame things down a little bit and allow us to clarify what's going on and treat it better.

29:14  Gall bladder problems can cause liver enzymes to riseSo again, what else could this be? Infections? Blood tests can be used. Gallstones can cause these [liver enzymes to rise], but usually that's associated with pain. It's very, very uncommon. I don't think I've ever seen asymptomatic gallstones. Also, infections of the gall bladder can occur. They can elevate the liver enzymes. Again, that's also something that is associated with pain, but can really elevate these liver enzymes. And oftentimes people have other symptoms of infection like fever and stuff. And finally, drug induced liver injury.

29:47  Treatment options if chronic graft-versus-host disease (GVHD) does not respond to steroids (steroid refractory GVHD):  So what do we do for refractory GVHD? If you have refractory, it's considered no response to treatment. Therefore, we've given you steroids, we've given you tacrolimus or something, and it's still not responding to treatment like we would like. We can do things that would be considered for acute GVHD.

So sometimes photopheresis or extracorporeal photopheresis. It's a time thing, because you're sitting there and they take your blood out and they expose it to medication and then put some UV light on it and then it goes back in your body. It's something I probably don't have time to discuss adequately with the time I have, but it is a treatment that we sometimes use.

Ruxolitinib is a drug that we've started to go to more recently, or Jakafi®. This is a drug that is used for patients with myelofibrosis, so it's FDA approved for myelofibrosis and polycythemia vera, but we're finding it can be pretty good for graft-versus-host disease because it really tamps down a lot of the inflammatory response.

CellCept®, mycophenolate, which is a drug some of you might already be on. Infliximab is a TNF alpha antibody. It's used less commonly. I think the data is not that supportive of it, but sometimes we still continue to use it. Another drug that's been approved for more chronic GVHD, I wouldn't necessarily use it as much in this setting, is ibrutinib. But again, that's something that I think that's more for true chronic, rather than a late onset acute like this.

31:16  Chronic graft-versus-host disease (GVHD) of the pancreas is rare. So, let's take case number four, moving away from the intestines and liver. Janet, she's a 65-year-old female. She's a year out from an allogeneic stem cell transplant, chronic GVHD of the mouth and the skin, and she starts noticing increasing abdominal pain, bloating, has really oily foul smelling stools, and has lost about 15 pounds over the last six weeks.

So ,oftentimes, this is a presentation that you'll see with pancreatic insufficiency. This is not a common finding in chronic GVHD, but it definitely can occur. And the nice part about this one is that steroids aren't necessarily the first thing you go to for treatment. You can go to just a pancreatic enzyme. But the pancreas is an organ. It makes insulin, is one of its things, but it also makes enzymes that help your food digest better. So, if you aren't able to digest the food, you aren't able to break it down and have it get absorbed in your GI tract like you're supposed to.

32:11  Symptoms of chronic graft-versus-host disease (GVHD in the pancreas: So clinically you'll see oily foul smelling stools, malabsorption, so you don't absorb stuff, which is why you lose weight. Bloating and cramping, because basically if food can't get absorbed right, it festers in the GI system and feels very uncomfortable. Vitamin deficiencies: this is something that's generally later on, but vitamin deficiencies in A, D, E and K. So they can present in a variety of ways, but also can be seen in blood tests, especially vitamin D. And vitamin K can make your blood clotting off. And you can have pain, especially with fatty foods, because a lot of what the pancreas produces  helps with fatty foods.

Now, pain with fatty foods can also be gallbladder, so again, these are all things that require more attention to and aren't just ‘Oh, I'm having this abdominal cramping. Let me go get some pancreatic enzymes from the store.’ It is something that needs to be evaluated, because it could be a number of different things. But it's definitely something you can see.

33:10  Treatment of chronic graft-versus-host disease (GVHD) in the pancreas:  So, treatment, sometimes it's just diet modifications. Sometimes it's just avoiding fatty foods and different foods that really require the pancreas to help. And there's also pancreatic enzyme replacement therapy, and there's lots of different formulations. There are some that are over the counter. I generally use CREON®, which is a prescribed one that you can do. You take it three time a day before meals. Sometimes if somebody is having a lot of symptoms but I can't find a lot of pathology, I'll just try this to see if it'll help, because it's a pretty benign treatment overall. And, also, no alcohol use because alcohol can really exacerbate anything with the pancreas, which is why alcoholics often get pancreatitis.

33:50  What you can do to prevent chronic graft-versus-host disease (GVHD) or minimize its effects:  So what can you do to prevent GVHD? It's really important to take your medications as prescribed. I know it sucks. Sometimes you're a year out from transplant, two years out, and you're like ‘Why do I still have to take all of these medications?’ But stopping it sometimes, especially if you stop it on your own, can really stimulate these symptoms to occur. So, it's very important to take the medications as prescribed, especially the immunosuppression ones, and then if you are tapering them to make sure you're paying very close attention to symptoms.

Also, avoiding alcohol. Alcohol can exacerbate almost anything in the GI system, in particular the liver and pancreas. But it certainly is something that can impact it. So, the discussion on drinking alcohol, and how much you can drink, is certainly one between you and your doctor, but it is definitely something that could potentially exacerbate some of these.

34:40  Don’t wait to call your doctor if you think you have graft-versus-host disease (GVHD) or things could get worseAnd what do you do if you think you have GVHD? Call your doctor. You don't want to wait, because delays can make the disease worse and the treatment last longer. And this is a hard one, because when you're out from transplant, you're nine months, the last thing you want to do I call your doctor and run the risk of being admitted to the hospital. But the thing to remember is that the longer you wait, the sicker you get, the longer you're in the hospital. So if you nip things in the bud, a lot of times you can take care of it more quickly, and sometimes not even have to go in the hospital. So I totally get it. I've gone through this discussion so many times with patients. Just call me. Doesn't mean I'm going to admit you. I'd rather know sooner rather than later because I can take care of it a lot quicker.

35:21  Managing the symptoms of chronic graft-versus-host disease (GVHD) of the GI tract with anti-nausea pills, small frequent meals, and nutritional supplements:  So now what do you do symptomatically? Because you have these symptoms. They're tough. So nausea is a big symptom that people can get, and a very hard one to treat. So, first of all, try taking anti-[nausea] pills 30 minutes before eating. I have some patients who are even a couple years out from transplant who have to do this sometimes. Eat small amounts and eat frequently: so instead of eating three big meals, or two big meals as some people do, eat small amounts every couple of hours. Try lots of different foods. If they don't taste good, don't force it. And, also, try to avoid your favorite foods, because the last thing you want to do is try to eat your favorite foods and then start to get really nauseous and then be turned off of that food forever.

Nutritional supplements can be good. Right now the nutritional drink thing is enormous. There's Boost® and Breeze® and Muscle Milk® and Rockin'[Protein Recover]®. You can find almost any supplement out there that you'll probably like. One that I like recommending is Carnation Instant Breakfast Powder®.  It's really cheap. You mix it with either milk or soy milk or almond milk or something like that. It's well tolerated, and it's an easy one to do, and it's the same nutritional quality as a normal Ensure®. Not like a super Ensure®, or Ensure Plus®, but just a normal one.

36:32  Sea-Bands® and ginger can help control nauseaOther things are Sea-Bands® and ginger. So, Sea-Bands® are these bands you can get. They're sold right next to the motion sickness medications in the pharmacy, and they use acupressure, put pressure right here on your wrist, and that sometimes can help. So that's a non-drug thing that you can do.

36:50  What to eat when you have chronic graft-versus-host diseaseWhat should your diet include? Basically, I say anything you can eat. Now, nutritionists may disagree with me on this one, but I feel like if you're not eating—I don't care if it's Cheetos that goes in you — I mean, unless you want to be careful with Cheetos if you have some types of GVHD, but whatever you can eat I want to get in your system. It's probably best to avoid fatty, spicy foods, especially if you have GVHD of the gut, and sometimes you'll have to eat a bland diet, but again, it's whatever you can get in at certain times. I say whatever you can get in, just eat, because again, we want you to do that.

37:26  Have patience – it can take a long time to recover after graft-versus-host disease of the GI system:  Anything else? Patience. This can take a long, long time to get better; and not being able to eat and having nausea is really one of the worst things. Just be patient. It can take a while to get better. Go and think back to the road rash thing and think of how long it takes if you get a good big scrape on your arm that's going your whole arm. It takes a long time to heal.

The gut's going to take a long time to heal too, and on top of that you're constantly stressing it by putting food in it,  which you have to do because if you don't put food in it, it really stops working. But it's definitely a give and take, and a long process. So don't lose hope, because I've seen people suffer with this for many months and still be okay on the other end; but it is something that you need to be very patient with.

38:10  Summary of talk:  So in summary, graft-versus-host disease of the GI system can involve the esophagus, the small intestines, large intestines, pancreas or liver. So, almost any organ system in that area can get involved. It's very, very important to identify symptoms early and to call your doctor. I can't stress that enough, because the last thing we want to do is have somebody come in saying they've been having these symptoms for a month, they don't get treatment, and then it becomes very, very dangerous and sometimes fatal; because it's important for us to get treatment started as soon as possible. And that's something that your transplant physician can really evaluate.  It’s what they need to do to make sure they give you the best chance of getting through this.

So, it's important not only to talk to your local doctor, but also make sure that your transplant center is in the know of what's going on, because the local doctors, they just don't ... I mean, if I had to treat colon cancer and breast cancer and lung cancer, it would be very hard to learn about graft-versus-host disease, which effects such a small number of people. So make sure, also, to talk to your transplant center.

39:11  Questions from the audience:  Thank you Dr. Palmer. We'll take questions now, and you're welcome to come up to the mic. If you would like the mic to come to you, just raise your hand and we will bring it to you.

39:26  Question about probiotics:  Hello. Thank you for today. I've had liver and gut GVH, and I'm definitely on the mend, getting a lot better. I'm off prednisone, weaning off tacro[limus], and still on ursodiol. I also take Bactrim® two days out of the week and have ever since. I'm three years old now. And so stools are inconsistent and cramping is less; but I'm wondering your thought on probiotics. I took some of those gummies, two of them a couple times a day, and I've seen improvement, and so I don't know ... I just wanted your thoughts on taking those probiotics.

40:06  Using probiotics and fecal transplants to manage side effects of chronic graft-versus-host disease (GVHD) of the GI system:  So, I personally think probiotics are a great thing, and I recommend them. I used to recommend Activia®. Always talk to your doctor. There have been a case or two where maybe there's a bacterial find in the blood that came from the probiotics. Again, I think that's rare—and maybe I've seen it once in the 10 years I've been practicing. But I personally think probiotics are a really good idea.

And one thing I didn't mention here, along that line, and this is something that's up and coming, and it sounds awfully gross, but it's a really interesting concept, it's fecal microbiota transplant Which is basically, what they do is, they take somebody - a normal healthy non-antibiotic person's poop - basically distill it down into a pill, and it has a lot of bacteria in it that will help recolonize your system in a normal way. But probiotics I think are good.

The other thing is, if you do feel like Bactrim® may be contributing to it… Bactrim® is extremely important for preventing PCP pneumonia, but there are other medications that can accomplish the same thing, and other treatments. So, that would be the other thing to consider talking to your doctor about. But again, probiotics, always discuss with your physician because there may be different extenuating circumstances. If somebody has really bad GI graft-versus-host disease where we're really concerned bacteria has a quicker rate of going through into your bloodstream, that might not be the best option. But depending on where you are at your time course, I think probiotics can be extremely helpful. I'm still trying to figure out what I should recommend as probiotics. I haven't gotten that savvy yet. I generally say avoid the super, super intense ones, you know, like ‘This has five million gazillion bacteria per ml,’ or something. Just stick with more standard ones.

41:49  Question: how do you know whether the symptoms you are seeing are chronic graft-versus-host disease (GVHD) or sclerodermaSo, scleroderma has a lot of the same symptoms that you've described here. How do you know which it might be?

So that's a really good question. So the question was asking about how scleroderma has a lot of these symptoms, so how do we know what these symptoms are from? And I mean, we see this a lot, because a lot of chronic GVHD in particular really mimics autoimmune disease. So you know, we haven't figured out the best way to do it, but I think working with rheumatology could be good.

Unfortunately ... so the bottom line is you're absolutely right, and I think a lot of the pathophysiology behind scleroderma is very similar to what you'd experience with graft-versus-host disease. The difference is, in scleroderma is it's your own immune system attacking you. In graft-versus-host disease, it's somebody else's immune system attacking you. But these immune cells can mediate the same type of attack. So, you might be able to ... so whenever somebody comes and they say ‘Well, I think I have Lupus, or I think I have this’ I'm like ‘Well, it doesn't matter. Any way you look at it, this is your immune system that is being dysregulated, attacking your healthy tissues.’

So, it's difficult, because especially when you have somebody coming in after a transplant, you're like ‘Well, how do I label you? Do I label you as graft-versus-host disease? Or do I label you as autoimmune disease?’ At the end of the day it's the same basic thing that's occurring, so you try to focus the treatments on suppressing the immune system.

Now, that being said, we are borrowing a lot from the rheumatologists in terms of drugs. For example, tocilizumab, which is an anti-IL-6 antibody, FDA approved for rheumatoid arthritis. It's made great differences in that, even juvenile rheumatoid arthritis. That's a drug that we've started using for chronic graft-versus-host disease. There are also other antibodies that have these crazy names like [inaudible].. I don't know. I can't do the names, but they're basically anti-IL-17 and stuff that we're really borrowing from the rheumatology community to use in graft-versus-host disease.

43:45  Question from audience: Photopheresis seems to help with symptoms of chronic graft-versus-host disease (GVHD). I had all of those symptoms, plus thickening of the skin, calves and arms, and started photopheresis and now have done about 36 sessions of photopheresis, and it seems to have helped with all of the issues.

Yeah, photophoresis is one of those generalized things that can help overall; and, if you try to say ‘What's the mechanism of action behind photophoresis,’ you have some people saying it activates the immune system because we use it against certain types of T-cell lymphomas of the skin. Other people say it suppresses the immune system because it creates tolerance of the immune system. So there's a whole bunch of hand waving involved with the mechanism.

But at the end of the day, especially for some of these chronic symptoms, I feel like it can be extremely effective. It's not for everyone though. You have to be lucky. You have to live near a center that will do photopheresis, and then you have to be there three hours, twice a week, for the weeks that you get it, because two sessions are one treatment. So it's a big time commitment that can be ... plus you need a central line or something in order to get it. So that adds an extra layer of complication, but it can be an extremely effective treatment if you're able to get it.

Audience member:  I asked my doctor how it worked, and he said ‘Oh, it's just voodoo that we do.’

Dr. Palmer:   Yes, I use that term a lot. It's our voodoo medicine.

45:09  Treating chronic graft-versus-host disease with cannabidiol:  I noticed recently there was some peer reviewed papers that came out about treating GVHD with cannabidiol, CBD. I was wondering if you had any experience with that or knew any patients that have had success with that?

Dr. Palmer:  So I don't know much about that. I really do believe that if we use the cannabinoids correctly that they could be a very good medication. I'm really excited that people are trying to do research with them, because the variety that comes with them is enormous, so I think there's definitely medicinal properties. I imagine it could be very good for the nausea and trouble with eating; and I suspect some of my patients might be using that type of therapy. Being from Mayo Clinic, I'm not supportive of it, but I think that when we try to consider it medicinally, I think we'll find some good things.

46:02  When you should call your doctor if you are having diarrheaSo the question was, what is the line where you know where it's just regular diarrhea or you should call? I always say, just call. I'd much, much rather know what's going on and have my finger on the pulse of it, because there's certain things that we'll ask that'll help us differentiate, like how you're doing with eating. Sometimes people come in and they'll be like ‘Oh, I'm having all this pain and diarrhea,’ and their electrolytes blood work will be really off, and that, to me, says this is a more severe problem than if they come in with those symptoms and the electrolytes are completely normal.

I think that patients are like ‘Well, I don't want to bother you.’  I'm like ‘I’m here to be bothered.’  It bothers me more when people don't call, because then I don't know what's going on, and things can get out of hand without my knowledge. So, I would say, if you have it and you're worried, call. That I have to trust ... I don't think there's a right answer there. You're right. If it occurs once and then it stops, probably you don't need to call. If it occurs twice and stops you might not need to call. But again, I think that whenever there's anything that's making you think ‘Could this be GVHD?’ it's just worth calling.

I mean, if you call and it's happened once I'll say ‘Okay, well call us if this happens two more times.’ Or they might say ‘Well geez, if you have a lot of cramping and large volume watery stool, we're going to want to know anyway because this could be C-diff, this could be something else.’ And there's sometimes simple tests we can do that are best to get done while we're waiting to see how things pan out as well. So again, there's not a perfect answer for that, because you're absolutely right. Everyone gets an episode of diarrhea here or there, healthy or unhealthy, and so where do you draw that line? And that's a very hard one to figure out, but I would say if you're thinking the question, then call.

47:50  Question from audience about shingles:  I've been troubled with a rash. It was on one hip and now it's switched over to the other hip, and at first they said it was shingles, but it was a light case because I had the shingles shot. But could this be the HSV?

Dr. Palmer:  Well, you know, it's hard to say because a lot of that ... first of all it's a diagnosis based on the location of the rash, what the rash looks like, the symptoms. Sometimes you don't know, you just treat empirically, because the treatment is acyclovir, which you can use Valtrex® three times a day, and that's adequate treatment doses. So it really depends on, it's very, very hard to say because rashes can appear in so many different ways. And shingles itself can appear in a lot of different ways.

Audience member:  Will shingles shift from one part of the body to another?

Dr. Palmer:  It can. If it encompasses more ... but usually they're very specific, especially if it's just like a plain shingles outbreak ,and not like a disseminated one. It's very strict on where on your body it affects, because the varicella virus, which is in the herpes family, lives in the nerves. So what happens is when it starts to reactivate and grow, it goes along where that nerve innervates. And we know that this has been very well defined, that each of the nerves carries a certain part of the body. There's pictures you can see that describe this. So, for example, if you take on of the nerves up here, it'll just do a strip across the body, and usually it's only one side or the other.

So yes, could it activate in one area and then the other? It could, but again, it's a tough diagnosis to make. I have a lot of patients who come in, and maybe they've had shingles, because I look at the rash and the distribution of the rash, and its appearance to me looks like shingles does, but they didn't really suffer that much from it and don't have pain, which is fantastic. But it's very hard to say. I mean, if you've had the shingles shot it's definitely not absolute protection though, is one thing. And ... so...

49:58  Question from audience about how long it can take to taper off prednisone:  So my husband had his transplant, it'll be two years in July, and it was a long hard road getting to it. We had two hospitals tell us to go home and die; so I mean, it seriously was a blessing getting to it. He had a little MRD after transplant, and then after that it's been pretty much smooth sailing.  And then around Christmas time he got the flu, and that started the whole chain reaction with the gut GVH and skin GVH. And so now he's taking 20 milligrams of prednisone a day. The doctor keeps telling him to taper down, but the minute he does, the cramping starts and the skin pops back up. Is that just something we're going to have to dance with for a while until things calm down? Or will they calm down? Or...

50:51  Association between infection and chronic graft-versus-host disease (GVHD): Right, so you asked some good questions about the flu. First of all, describing the flu associated with GVHD. One thing that is really common is that if you get an infection, once your immune system gets revved up, it can also rev up not only the things that are going after the flu, but also affect graft-versus-host disease. So sometimes, if somebody has a cold and they get a flare of GVHD, I have to hold my hands down and go ‘No more prednisone,’ because once the cold goes away the GVHD get better. Again, that's definitely something that your doctor will determine. It's not something that I would recommend doing on your own; but it's very common once you see infections, graft-versus-host disease and infections go hand in hand.

51:35  Tapering off steroids:  Now, in terms of the other question which was asking about trying to taper the steroids, this becomes a dance, you know, and everyone manages it a little bit differently. Sometimes we'll add on non-steroid immunosuppression medications because then, at least, we're getting you off the steroids, which probably have more deleterious effects than some of the other immunosuppression drugs. Sometimes topicals are used, like the budesonide or beclomethasone, which are not absorbed to the same degree prednisone is. It's very tenuous, but you're right, there's a dance; and it's a dance we all try to play because we all definitely want to get people off of steroids. Steroids are not a drug we want to keep people on if we can help it. And you have to keep testing that boundary, but testing the boundary often times means a flare of the symptoms where you have to go back up.

Generally speaking, and this isn't 100%, graft-versus-host disease burns itself out after a while. Eventually, the body and the immune system figure out how they're going to live together. Primarily it's teaching the immune system to live in the body it's in. So eventually I tell people there's a light at the end of the tunnel. Now, you might have scar tissue that will still persist, but at least some of the active inflammation with be gone. Now, that's not in everybody, but in a lot of patients, even those who have had pretty severe GVHD. But the dance is very normal.

52:56  Audience questions about photopheresis:  We asked the doctor about the photopheresis, and he's a man of few words, and his response was ‘Not yet.’

Dr. Palmer:  Yeah, and that I would, you know, that is something that you would, that is again, a discussion. It's a time commitment to do. Obviously the side effects of it are pretty minimal, but it still can cause anemia. It's still a matter of taking the blood out, having a central line which can cause infections. So it's definitely not a step to be taken lightly. So I think there's a lot of different things that your doctor may consider. If it's just 20 milligrams of prednisone, a lot of times you can try some other interventions instead, and not have to have the trouble of a central line and everything else. So I would certainly trust your doctor's judgment on that. Because again, photopheresis does come with its own price.

53:49  I think we have time for one more question in the back. Did I miss somebody? I think that girl.

53:58  Questions from audience:  Does a time ever come when you can say your symptoms are definitely not GVHD?:  Hi, so I know that if you have acute ... sorry, I lost my voice. My allergies are terrible here. I know if you have acute GVHD when you're inpatient, you're more likely to have chronic GVHD after. Is there ever really a time that you can say ‘Okay, all of these GI problems are not likely to be chronic GVHD?’  As a backstory, my daughter is four years out. She had acute [GVHD], and then it ended up turning into a chronic GVHD with liver and gut involvement, photopheresis, steroids, and now she's starting to exhibit some of those same symptoms again; and we're getting to the point to where we're talking about a scope, trying to figure out whether or not it's GVHD or maybe something else that's attributing to her problems. Is there every really a time when you can say ‘Okay, I'm finally five years, I'm finally 10 years, it's not likely to be GVHD at this point?’ Is there ever really a safe zone?

Dr. Palmer responds:  Well, I think ... so the question was about, just in case the microphone didn't get it, the question was about was there ever a time where you can say ‘This isn't GVHD?’ So, I think that's a hard one to answer. I don't think, maybe after 10 years if you've never had any GVHD, then perhaps. The other piece of that, especially in the case of somebody who's had acute and chronic, the immune system does not grow and develop appropriately.

So, if you've had acute and chronic, there's a chronic immunosuppression that occurs, that takes the immune system a very, very long time to reach the same degree of ... be able to attack the same degree of viruses and bacteria and stuff. So even in that type of case, it might not be graft-versus-host disease, but it also could be that because of the chronic immunosuppression, that it could be a viral infection. So it's always important to look at that. Now, when you can say you're done with it entirely, that's a really good question. I don't think I have a good answer for that.

Audience member:  It was a loaded question, so, just thought I'd try.

56:10  When to taper off Jakafi®It's hard to say. So the question was that somebody's been on prednisone, off prednisone for a long time, but [is] on Jakafi®. Is Jakafi® still what's keeping it[chronic GVHD]  in remission? And the only way to know that is to talk to your doctor about whether tapering would be appropriate or not. The good news about Jakafi® is that, in the many other things it's treating, like myelofibrosis, and especially polycythemia vera, we are seeing it used over a long period of time. But again, no drug is without its side effects. You know, Jakafi® does suppress the immune system, so I think, again, it could be what's holding it.

It's one of those things where you're like ‘Do we take the plunge and try to take it off? Or do we just say we're going to deal with it?’ And that's something that is very person-to-person dependent, and different doctors treat it differently. I tend to be really aggressive about getting people off immunosuppression; and it has probably bit some people by me doing that, but then some people probably get off those drugs, whereas I have colleagues who keep them on tacro[limus] indefinitely, which has its own set of side effects.

So, there's not a perfect answer for that one; and it's definitely a personal conversation you have with your doctor in terms of whether you want to take that plunge. I think, especially with steroids, I always take the plunge and say, ‘Let's try to get you down, because we want to get you off steroids.’ When it comes to something like Jakafi®, where we do have cases where people have used it for a long period of time, I mean, fairly long, probably five, six, seven years at least, then it becomes a little bit more tricky to say ‘Well, what do we do with this medication?’

And again, that really depends on how many drugs we had to use to get somebody to a good spot, if there's any negative side effects with the drug that they're on that would make me decide to take it off. So, it's a very personal decision; but I usually am in favor of it if things have been stable for a while, try to get the drugs off. But again, it's not a cut and dry answer. It's not something I can just say ‘This is something you should do no matter what.’

58:09  Question from audience:  Could Jakafi® be better than steroids?

Dr. Palmer:  The question was, is Jakafi® better than steroids? Well, the side effect profiles are different. Personally, I think anything that [if you] can spare steroids [it] is probably a good thing, and something worth considering. That being said, Jakafi® can sometimes be very tricky to get for graft-versus-host disease. But it is something worth talking to your doctor about because, again, it's one of those newer things that's come out.

Well, we might end up finding out that it doesn't work as well as we think it does, but I think we've all seen cases where it does work in graft-versus-host disease. And again, the side effect profile for that one and the immunosuppression mediated by that one is, I think, is probably a little bit less than some of the other medications we use. But again, you know, using it in transplants is still very, very, very new. We don't have a lot of long-term data on it, so I think that it is something to use ... you know, I think it's a good drug, but I also think it's one to use with caution.

59:07  Thank you very much Dr. Palmer. We appreciate all your information.


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