Ask The GVHD Experts

(00:00:00) Michala O'Brien: Welcome to the webinar, Ask the GVHD Experts. It's now my pleasure to introduce our speakers. Dr. Amin Alousi is a professor of medicine in the department of Stem Cell Transplantation & Cellular Therapy at the University of Texas MD Anderson Cancer Center. He is the medical director of the Multi-disciplinary Graft-versus-Host Disease Clinic and Research program, as well as the medical director of the Stem Cell Transplantation & Cellular Therapy unit.

(00:00:27): Dr. Michelle Bishop is a clinical health psychologist with over 30 years of experience in helping patients and families cope with cancer, cancer survivorship, and caregiving. She spent the first half of her career at the University of Florida, first as a clinician providing care to bone marrow transplant families and patients and later conducting BMT quality-of-life research. She currently sees patients in her private practice, and she spearheads BMT InfoNet support groups for GVHD patients and their care partners. Welcome, Dr. Alousi and Dr. Bishop.

(00:01:08): Our first question is for Dr. Alousi: Briefly explain what GVHD is, and the difference between acute and chronic GVHD.

(00:01:18) Dr. Amin Alousi: Thank you, Michala, and thank you, BMT InfoNet, for inviting me to be with you guys tonight. We have an excellent list of questions, and I'm honored to be here with Dr. Bishop.

(00:01:31):  So, what is graft-versus-host disease? In the simplest terms, graft-versus-host disease is a complication of stem cell transplant in which the donor's immune cells, called the graft, react against the recipient's tissues, the host, as if they were foreign.

(00:01:53): There are two types of graft-versus-host disease. There's acute graft-versus-host disease, and there’s chronic graft-versus-host disease. We believe these are distinct, interrelated processes. 

(00:02:06) Acute GVHD typically happens within the first couple of months after the transplant, and it mainly occurs in three organs: the skin, the GI tract, and the liver.

(00:02:22): The skin is often the most common organ involved and has a very typical rash that is described as maculopapular. It's basically a red, bumpy rash that your clinician and your team would recognize.

(00:02:35): The GI tract can present with nausea or persistent nausea after the transplant, poor appetite, and weight loss, or it can present with diarrhea.

(00:02:47): And then when the liver is involved, and this is much less common, we see changes on labs with elevation in certain liver function tests, like the total bilirubin or alkaline phosphatase.

(00:03:01): Acute graft-versus-host disease typically happens within the first couple of months after the transplant, but it can really develop at any time after the transplant, and we can see it even later. This can occur, especially when immunosuppressants such as tacrolimus or cyclosporine are being tapered off. And so that's another period where we may see acute GVHD happen beyond the first couple of months after the transplant.

(00:03:29): Chronic graft-versus-host disease is different. It typically occurs, on average, at roughly five to six months after the transplant, with most chronic GVHD manifestations happening within the first two years after the transplant.

(00:03:46): Chronic graft-versus-host disease can look much more like autoimmune conditions that you may have seen patients have who've never had a transplant. It can present with ocular involvement, causing dry eyes, or oral involvement, causing mouth sensitivity when patients eat spicy or acidic foods. 

(00:04:11): Chronic GVHD can cause various types of rashes that can happen in the skin that we monitor for. It can also involve the genital system in both women and men and can affect the joints, causing stiffness. And so there are two distinct entities that we recognize based on how they present.

(00:04:36) Does everyone develop GVHD after transplant? Is the incidence and severity of GVHD decreasing?

(00:04:45) Dr. Amin Alousi: Not every patient develops graft-versus-host disease after transplant. The incidence, in fact, is decreasing, and that's one of the great successes of transplantation. The risk of graft-versus-host disease has changed immensely in the 20-odd years I've been in practice. For every five years since 2000, the incidence of graft-versus-host disease has consistently declined.

(00:05:17): Currently, about a quarter to a third of patients develop acute or chronic graft-versus-host disease. That's much less than it was just 10 or 15 years ago.

(00:05:32): Importantly, while graft-versus-host disease still occurs in about a quarter to a third of patients, the severe and most life-threatening forms have fallen dramatically, with an incidence of about 5 to 10% of cases.

(00:05:59) What are the most common symptoms of chronic GVHD that I should watch for after transplant?

(00:06:06) Dr. Amin Alousi: There are eight organs that most commonly show manifestations of chronic GVHD, if it's going to occur. BMT InfoNet has excellent educational materials on chronic GVHD and its manifestations.

(00:06:30): The symptoms in the eyes are dryness or irritation, especially when you're focusing on a computer screen or your phone. When it's windy outside, you may feel a burning sensation or a foreign-body sensation in the eye.

(00:06:48): Manifestations in the mouth would be sensitivity when you eat spicy or acidic foods, which causes burning or pain in the mouth.

(00:06:55): When the skin is involved, there are various manifestations and unique rashes that occur. Some of the more common manifestations would be thickening of the skin. It almost looks like scar tissue formation.

(00:07:11): The lungs can be involved, and typically, patients do not have symptoms early when the lungs are involved. We only detect lung involvement by doing monitoring tests, such as pulmonary function tests, after the transplant.

(00:07:26): There may be genital manifestations in both men and women. In women, this may manifest as pain with sexual intercourse or asymmetry in the external genitalia or itching or pain in those areas. In men, it is typically redness and tenderness at the head of the penis or at the foreskin.

(00:07:54): Nails can be involved. These are the most common manifestations of chronic GVHD that your clinicians will be monitoring for and educating you about throughout the process.

(00:08:09) The next question comes from a survivor who had moderate acute GVHD. "It took me two years to get off immunosuppressants. What is the chance that I still could develop GVHD three and a half years after transplant?"

(00:08:26) Dr. Amin Alousi: The good news is if you have now been off of immunosuppressants for an extended period and you have not shown any manifestations of acute or chronic GVHD, then it's not likely to occur at a later time point. The risk never goes completely down to zero, but most graft-versus-host disease manifestations will happen while you're on immune suppressants or in the months, maybe three to six months, to maybe as far as a year after stopping the immunosuppressants. And so if you've been off immunosuppressants for an extended period, in this case a year and a half, the chances are pretty good that chronic or acute GVHD manifestations will not occur.

(00:09:23): And for chronic GVHD, the majority of chronic GVHD manifestations happen within the first two years after the transplant. So, if you're now four or five years out from the transplant and you don't have any manifestations of graft-versus-host disease, then it's unlikely for you to develop it later. The risk is never zero, but it's very unlikely in that situation.

(00:09:50) Do people with GVHD have to take immunosuppressant drugs lifelong?

(00:09:57) Dr. Amin Alousi: No. Immunosuppressant drugs are the mainstay for the treatment of both acute and chronic graft-versus-host disease. The pace at which these immunosuppressants are tapered or stopped will depend on the severity of GVHD. Ultimately, the goal is to stop immunosuppressants over time.

(00:10:24): If a patient has a prior history of severe acute or chronic GVHD, we may be more cautious and taper them more slowly with close monitoring. But the goal is to, at some point, get off these medications. With that said, maybe as many as 20 to 25% of patients who have a prior history of GVHD may need these medications lifelong. And so it is possible that some patients need these immunosuppressants for a longer period, or even lifelong. It really depends on the clinical scenario.

(00:11:06) How long do I need to worry about chronic GVHD returning once it is resolved? How can I reduce the risk? How can I cope with the constant worry that it will return?

(00:11:20) Dr. Amin Alousi: For chronic GVHD, once you've been off of the immunosuppressants for an extended period, say three to six months or maybe a little bit longer, and you don't have any new manifestations of chronic GVHD, then there's a good chance that you're out of the woods.

(00:11:52): How can you cope or how can you manage? Well, education is the best way. So, know the various manifestations of chronic GVHD. Like anything in medicine, it's always easier to treat it at its earliest onset. If symptoms return, maintain open communication with your care team and report them promptly. If you're not sure whether it could be a manifestation of GVHD or not, ask. Early patient reporting is really beneficial for outcomes. And so that's number one.

(00:12:33): Number two, if you have a prior history of chronic GVHD, it is a good idea to see your primary transplant providers and/or a graft-versus-host disease specialty clinic where they can monitor for any signs of progression, even symptoms that you may not have recognized in yourself. And by staying in frequent follow-up with your care team, that's an important way to monitor a patient with a prior history of GVHD and be assured that it is not coming back.

(00:13:13) GVHD caused changes in my skin pigmentation. Will that ever clear up? What can help with that?

(00:13:22) Dr. Amin Alousi: So, changes in skin pigmentation are often very troublesome for patients because they affect appearance and how people see you. It's also a constant reminder of your graft-versus-host disease and your transplant process. There are many reasons why pigment changes occur. It's hard to say, without knowing the specifics, how long the pigment changes may last. Certain pigment changes may be short-lived, lasting weeks or months, while others, unfortunately, can be more permanent. So it's really hard to say without knowing you and your medical history.

(00:14:11): What can be done about it? Well, some dermatologists specialize in pigment disorders, and oftentimes seeing one of them is really important. They may recommend specific, simple fixes, such as specialized cosmetics tailored to these medical causes of dyspigmentation. Occasionally, other interventions, such as topical therapies, may help restore pigment in the skin, depending on the underlying cause of the pigment changes.

(00:14:46): I would say seeing a dermatologist, especially one who specializes in those manifestations, is really important. Seeing specialists who are very familiar with graft-versus-host disease is a really important way to help manage its symptoms and treatment. I encourage your audience that, if they live close to a center that has a multidisciplinary GVHD clinic where you have a dermatologist, pulmonologist, or gynecologist who is familiar with the disease, often that's really helpful in dealing with and getting the best treatment.

(00:16:03) I heard that sunburn can cause GVHD to flare up and cause skin cancer. What should I do to prevent this, and is it temporary?

(00:16:14) Dr. Amin Alousi: Yes. There are reports of patients sunbathing and getting excessive sun exposure, triggering an immune response in the skin. In general, it's not a good idea to sunbathe, and it is best practice after a transplant, whether you've had graft-versus-host disease or not, to wear sun protectants. And that includes a wide-brim hat, long-sleeve shirts, and sun-protectant lotions, typically with an SPF of 30 or higher.

(00:16:55): And this is not only to ward off developing graft-versus-host disease, but more importantly, once you've undergone a bone marrow transplant or a stem cell transplant, you are at increased risk of skin cancers, and avoiding excessive sun is important to reduce your risk. Really, none of us should be sunbathing, and we all, whether we've had a transplant or not, should be taking steps to avoid excessive sun exposure. It's best practice to prevent skin cancers later in life, which is, after all, the most common form of cancer there is. This really applies to the family as a whole, not just transplant recipients.

(00:17:47) GVHD is affecting my joints. What can I do to increase flexibility in my fingers? I already do physical therapy. How can I prevent the joint pain from getting worse?

(00:18:00) Dr. Amin Alousi: Such a great question. When graft-versus-host disease involves the joints and the fascia and limits mobility, in addition to medications, dedicated therapists can often improve flexibility and range of motion in those joints. You mentioned that you're working with a physical therapist. Oftentimes, occupational therapists, in addition to physical therapists, are really important here.

(00:18:31): Occupational therapy is a distinct discipline from physical therapy that looks at how we function in our day-to-day living. Often, occupational therapy can not only work to improve mobility through stretching and very dedicated exercises but also use specialized tools and devices, as well as casting, to increase the flexibility of those joints, especially if there's a significant restriction. And so, if you can see an occupational therapist, ideally in a graft-versus-host disease clinic, who has experience with treating this manifestation, it is often very beneficial. In my graft-versus-host disease clinic, we have a wonderful occupational therapist who has frequently done wonders, even beyond drugs, to improve mobility. So, seeing a provider with that expertise, I believe, is very important.

(00:19:44) I have been treated for chronic GVHD by a dermatologist for several years. I've had several flare-ups of vulva inflammation, swelling, and hemorrhoids. Tacrolimus and prednisone are not helping. How common is this? What can help?

(00:20:01) Dr. Amin Alousi: So, based on the question, it's hard to answer without access to your medical records or without seeing you in person, but it sounds like you have genital involvement from your GVHD. Genital involvement in females happens in about 5 to 10% of patients, we believe. It may be slightly higher because screening is often not done as routinely as it should be. But in general, about 5 to 10% of women may develop vaginal involvement.

(00:20:40): In addition to topical therapies, systemic treatment with the topical therapies can help with those manifestations.

(00:20:49): Working with a dedicated therapist helps with all of those manifestations that you alluded to. There's a special therapist called a pelvic floor therapist. This is a subspecialty of physical therapy where they specialize in diseases of the pelvic floor, and that would help with the manifestations that you're experiencing, including the vaginal involvement.

(00:21:18): Often, when there's vaginal involvement for other reasons, women may experience hemorrhoids or sometimes recurrent urinary tract infections. And pelvic therapists, especially those who are familiar with graft-versus-host disease, can be really instrumental in providing symptom relief for women who have this manifestation. And so seeking out a pelvic floor therapist who can do very dedicated therapy, directed at your symptoms, is really very, very helpful for women with these manifestations.

(00:22:01) I have chronic mouth sores due to GVHD. How can I best manage the pain?

(00:22:08) Dr. Amin Alousi: When a patient has oral graft-versus-host disease, in addition to sensitivity when they eat certain foods, such as spicy or acidic foods, some patients can develop frank ulcers. It's important to be evaluated by your transplant team to see whether your immunosuppressants need to be adjusted or whether newer agents, such as Jakafi (ruxolitinib), Rezurock (belumosudil), Niktimvo (axatilimab), or one of our newer therapies, would be helpful for you in that manifestation.

(00:22:48): Beyond immune suppressants, working with oral specialists to treat these manifestations can be beneficial. In my clinic, we have an oral pathologist who sees patients, and often when we have ulcers that are slow to heal, we can inject a small amount of steroids into them to speed up healing. And so, treatments such as topical steroids can be employed, and sometimes systemic treatments are needed to keep these ulcers or the pain that you're experiencing from coming back.

(00:23:37) How often does GVHD affect the lungs? What are the best treatments?

(00:23:44) Dr. Amin Alousi: It's really hard to speak as to what the best therapy is for any given patient. It really comes down to the patient's GVHD level and manifestations, and any concerns we have about side effects in that specific patient. Lung graft-versus-host disease happens in roughly 5 to 10% of patients who experience chronic GVHD. It's not one of the more common manifestations of GVHD, but it is one of the more serious.

(00:24:20): The best way to treat chronic GVHD is to recognize it early and start therapy promptly. Lung GVHD, when it first begins, often does not have any symptoms, so having screening pulmonary function tests done in the first two years after the transplant is really important to recognize early manifestations of chronic GVHD and intervene early to prevent further progression.

(00:24:51): With that said, the newer agents have resulted in some encouraging results. Rezurock (belumosudil) has been shown in trials to benefit a subset of patients with lung GVHD. Our newer agent, Niktimvo (axatilimab) has shown some promise in lung GVHD. Jakafi (ruxolitinib ) has also shown promise in that area.

(00:25:23): An old therapy called extracorporeal photopheresis has sometimes been used and has been beneficial. I think the take-home message is to screen for lung GVHD early with pulmonary function tests, have your clinician recognize early manifestations, and start therapy early if they are observed.

(00:25:45) Do GVHD and drugs used to treat it increase my risk for developing new cancers after transplant? What can I do to decrease the risk?

(00:26:00) Dr. Amin Alousi: Just by having a transplant and being immunosuppressed or immunocompromised, transplant patients are at increased risk for secondary cancers. The most common one is skin cancer. How do we prevent that? By avoiding excessive sun, seeing a dermatologist at least once or twice a year to screen for any lesions that may be of concern, and maintaining good cancer screening.

(00:26:34): If you're a female, mammograms are important. Getting a colonoscopy is important. But in terms of secondary cancers, graft-versus-host disease, and being immunosuppressed from its treatment, can increase the risk of secondary cancers.

(00:26:52): In addition to skin cancer, there's also a potential risk of oral cancer, especially if a patient has had prior oral graft-versus-host disease. And so seeing a dentist twice a year who can examine the mouth and recognize any lesions of concern, similar to how a dermatologist would examine a patient twice a year, is important in the screening process.

(00:27:24) GVHD scares me. I know it affects patients differently. Is there any way I can prepare myself before transplant to handle GVHD?

(00:27:47) Dr. Amin Alousi: How can you prepare yourself when you're undergoing a transplant for the possibility of GVHD? Just understanding the manifestations of GVHD and promptly reporting them is really important. Taking your medicines as prescribed is really important. After the transplant, patients are on numerous medicines, and sometimes it's hard to keep track of them; taking drugs consistently can be a challenge, but taking your medications is vitally essential to reducing your risk.

(00:28:22): Your care team undoubtedly is using the best therapies to prevent GVHD. The good news is that we've come a long way in the past 20 years, and the risk of graft-versus-host disease is much lower than it once was. It's still something everyone should pay attention to and be familiar with its manifestations. Knowledge is power, and the best way to cope with it. But perhaps Dr. Bishop may have some additional suggestions to help with the mental toll of the fears related to GVHD. Sounds like this patient is worried even before he or she has gotten to the transplant about this potential risk. Dr. Bishop?

(00:29:08) Dr. Michelle Bishop: Absolutely. Thank you so much, and thank you, Michala and BMT InfoNet, for the invitation to be here tonight. I really appreciate the opportunity to participate with Dr. Alousi.

(00:29:19): So, when facing uncertainty, we can't prepare for every possibility, but we can build resiliency for whatever comes. And so whatever twists and turns on the road may bring, we feel that we have the capacity to handle it.

(00:29:41): And so one of the first things we can do would be building confidence and competence, and we do this through gathering information. I couldn't agree more with Dr. Alousi. Get information from the medical team and from other resources. In fact, you all are doing this right now by participating in this webinar. So, learning about the landscape and what to look for along the way helps you to get a sense of what to expect, and really is empowering.

(00:30:11): You can learn from your medical team, of course, from webinars such as this, from written materials, and other recorded webinars and podcasts available at BMT InfoNet and other organizations.

(00:30:24): You can also think about getting information from folks who have been on this road before you, specifically, folks who are post-transplant and living with GVHD. They provide a whole other perspective on what it's like to live with GVHD, how they've coped with it, and how they've managed it. And so I think that can be really invaluable.

(00:30:53): Sometimes at your transplant center, your team will connect you with a survivor that you can talk to. BMT InfoNet and other organizations also offer peer-to-peer support programs that connect you with someone who is matched based on specific criteria, who is a little bit further ahead on that road than you. That can be an invaluable resource. (see bmtinfonet.org/caring-connections)

(00:31:20): Second, build resiliency. Resiliency is the ability to adapt, recover, and bounce back from adversity. So, building confidence and competence with information.

(00:31:32): Then, build social support. You can't go this alone, you don't want to do this alone, and you don't have to do it alone. There are all kinds of social support along the way. Obviously, your medical team and the allied health professionals on your team are primary sources of support.

(00:31:53): But remember, there are a lot of other sources of support - your personal supports like your spouse, partner, caregiver, family, friends, neighbors, coworkers. They're there for the long term, and you want to let them in. You may need to educate them, particularly when you're talking about GVHD, because many folks aren't familiar with it and may be confused at first. "Why are you dealing with something now after the transplant? I thought you had your treatment. I thought you were done." So just educating them, communicating with them about what's going on, and about what you need. I think folks are happy to be of help.

(00:32:39): Other sources of help are folks who have been through it before, because they get it in a way that maybe no one else can. That could be peer-to-peer support, someone at your local center. As Michala mentioned, BMT InfoNet runs GVHD support groups for both caregivers and survivors. We've been doing this for about 6 years, and it's been really successful and really inspiring, frankly. I've been a facilitator for some of those groups, and to see the support, information, and inspiration that folks offer one another is really something. (see bmtinfonet.org/support-group-list)

(00:33:28): A couple of other things. One is self-care; although there's a lot you can't control, there's a lot you can. So, take care of your overall health the best you can, sleep, rest, nutrition, and stress management.

(00:33:40): And of course, don't forget about mental health. Find ways to express and process emotions, because there will likely be a lot along the way, such as fear, sadness, and frustration. That's self-care as well.

(00:33:53): And if you think about it, it's like this: if you're on a road trip, and if your car is in the best condition possible, with air in the tires and gas in the tank, you can more easily maneuver. You can more easily shift and adjust to the course, whatever challenges come up on the course, if you're overall ready, both mentally and physically.

(00:34:18): If you need extra support, for instance, from a mental health care provider, BMT InfoNet has a directory of mental health providers who have experience with BMT survivors and folks living with GVHD. So that is a nice specialty resource that you could check out. (see bmtinfonet.org/mh-directory)

(00:34:40): Think about perspective and meaning. We can get so focused on fear and the 'what-ifs', that it's important to stop and re-shift to 'what is': what is true right now, and what in your life is positive and meaningful. We're not talking about pushing a lot of positivity, but rather about counterbalancing worry or challenge with things you appreciate or are thankful for.

(00:35:23): And sometimes zooming out and remembering, "okay, why did I do this in the first place? What gives your life meaning, and what have you gained from having been through this process?"

(00:35:39): I will tell you lastly, after doing these GVHD support groups for over six years, with folks who are experiencing moderate to severe GVHD. I would say 98-99% of the folks say that they don't regret having gone through transplant despite the challenges that they're experiencing, even when some of those challenges continue for some time. And again, the support, information, and, if you will, love offered in these groups is really inspiring.

(00:36:23): So there's a lot that comes from any adversity. Ultimately, we can't plan for those specific outcomes, but if we can really build our resiliency and your confidence and feel that, no matter what, you can cope, problem-solve, advocate for yourself, get information that you need, and the social support - your medical team and so forth - then you can manage whatever comes.

(00:37:01) Dr. Amin Alousi: Wow, that was wonderful, excellent advice from you. Yes, our patients are among the most resilient you will ever find, and we're constantly in awe of the body's ability to adapt to challenges and for patients to remain resilient, especially when they're prepared. That's wonderful. Thank you.

(00:37:25) How does GVHD affect patients mentally? Is this mostly drug-induced?

(00:37:33) Dr. Amin Alousi: How GVHD affects patients mentally is a complicated question. There can be side effects of medicines, specifically steroids, that can play havoc with your emotions and make you maybe a little bit more labile, especially when you're on higher doses. But even when we're tapering dosages, that can affect how we feel emotionally. And so, definitely a side effect of medication, specifically steroids, can play with your emotional health.

(00:38:14): GVHD is obviously a stressor, and any stressor can affect how we feel, our emotions, and how we respond to the stimuli in the world around us. GVHD itself doesn't typically manifest with changes in emotions, but within the context of having a chronic medical condition, certainly, that can do so. But I would love to hear Dr. Bishop's thoughts on that, as someone who spent her career focusing on that.

(00:38:48) Dr. Michelle Bishop: I couldn't agree more. It is, of course, incredibly complex. Our mind and body are inextricably interwoven, so we really can't separate the two. Certainly, medications, fatigue, pain, and different physical challenges affect our mood and vice versa. Other things that can affect one's mood are adjustments needed to live with GVHD and being a transplant survivor with a lot of changes: changes to the body, changes to one's identity, changes to the current life and lifestyle, and the ability to continue some of the activities that one did before transplant, and one's imagined future may be different. There can be a lot of change, loss, and grief that comes with that. And that can be really important to recognize and work with, because it is possible to grieve, work to accept and adapt, find new ways to do old things, and manage, express, and process whatever emotions are coming up.

(00:40:22): Be aware of emotions like depression, anxiety, fear, frustration, and so forth. If those emotions feel too much to manage by journaling, talking to friends and family, and so forth, you can seek professional help from mental health professionals, such as psychologists or social workers. These licensed mental health counselors can help with adjusting to and processing the emotions that may come up.

(00:41:14) Our final set of questions focuses on the future of GVHD. Dr. Alousi, I've had chronic GVHD and fatigue for over three years. I exercise, eat nutritious foods, sleep well, and stimulate my brain. How can I improve energy and stamina?

(00:41:36) Dr. Amin Alousi: Well, it sounds like this patient is already doing the most important things to do, but even with eating right, sleeping, and exercise, fatigue can be just a manifestation of GVHD and/or its medications, and be challenging. And so, number one: ask your provider, "Is there a medical reason for the fatigue I'm feeling?" Sometimes it's due to coming off of steroids, and sometimes we need to replace the body's natural steroids in those situations.

(00:42:22): There are specialty clinics to manage fatigue in cancer survivors and cancer patients, and often, those specialty clinics can be very beneficial. And so, I would say doing the things you're doing and asking your provider whether there are any additional reasons for the fatigue you're experiencing would be most beneficial. Dr. Bishop, have you come across anything when you're talking to patients that may help, from a mental health perspective, with fatigue?

(00:43:00) Dr. Michelle Bishop: All the things that this person is doing, I would absolutely agree with. It sounds like they're really doing all they can. Always keep an eye out for the psychological, emotional, and mental aspects. Fatigue can certainly affect mood, but mood can also affect fatigue. So again, if there are any symptoms of depression, anxiety, anger, frustration, or grief, those can consume energy too. And so that would be one additional area to take a look at to see if there's room for some extra self-care, because, again, this person is certainly doing such great things to take care of their physical body.

(00:43:56): And I think pacing, too, which they refer to in terms of exercising and doing little bits, but pacing socially, saying no if you need to. Also, know yourself, so really observe. Sometimes there are patterns to fatigue, and so it may be that mornings are a little bit better, there's a little bit more energy. So that's a good time to do certain things and then to rest later. So, really trying to go with the grain instead of against it, and always be thinking broadly in terms of both body, mind, and heart care.

(00:44:45) My adult daughter's GVHD is very aggressive. When she gets GVHD flares, she's treated with high dosages of steroids. Now she has avascular necrosis in three joints. What can be done to avoid more joints from getting avascular necrosis?

(00:45:03) Dr. Amin Alousi: That's a great question. I'm sorry to hear that your daughter's experiencing not only the graft-versus-host disease, but complications of its therapy.

(00:45:14): Avascular necrosis is a side effect of long-term use of steroids, and it's often more common in younger adults, teenagers, and young adults. The best way to mitigate its development in other organs is to determine whether steroid-sparing agents would be beneficial in controlling this patient's graft-versus-host disease. Again, it's hard to know without the medical history and more specifics, but we often use second or additional agents to control those flares when they occur.

(00:45:59): A patient may not be resistant to steroids, but the fact that it occurs as they're being tapered off means they're dependent on steroids. In those situations, often turning to new lines of therapy would be important. Typically, if a patient has had more than one or two flares of their GVHD as they're coming down off of the steroids, one would typically look to start a new line of therapy to help get them off the steroids and to mitigate against those flares as they're being tapered.

(00:46:39) I was diagnosed with lichen planus skin GVHD, and I've been on prednisone for three years. When I tried to taper off, the rash came back really badly. I have significant weight gain, moon face, and was recently diagnosed with osteoporosis. Are there other treatments I can try to control my GVHD?

(00:47:04) Dr. Amin Alousi: Lichen planus often is a manifestation of chronic GVHD that does respond to non-steroidal forms of treatment. This would include treatments such as light therapy and extracorporeal photopheresis, as well as newer agents such as Jakafi (ruxolitinib), Rezurock (belumosudil), and Niktimvo (axatilimab). All of these drugs and therapies have been shown to result in a response in patients who have lichen planus manifestations. And so, looking towards one of these agents in lieu of the steroids sounds like it would be appropriate, and I suspect the provider caring for this patient has already begun some of those things. But we now have more and more lines of therapies to try to prevent the recurrence of the skin manifestation called lichen planus that this patient is experiencing when the steroids are being tapered.

(00:48:40): Finally, I would just point out that sometimes when the rash comes back, it may be a new type of GVHD or even a non-GVHD rash. So, repeating biopsies in these patients can be beneficial to determine whether the manifestation is the same disease as previously experienced. Certain skin conditions that commonly present with tapering of steroids are not GVHD in and of themselves and may benefit from therapies directed at those manifestations. So sometimes, if it recurs multiple times, repeat skin biopsies are important to make sure we're still dealing with the same entity.

(00:49:29) My husband had myelodysplastic syndrome, MDS, and a stem cell transplant four years ago. He's currently on Jakafi (ruxolitinib), which makes him immunocompromised. We are still wearing masks. How much longer do we need to be concerned about germs or viruses?

(00:49:54) Dr. Amin Alousi: It's tough to answer for any one specific patient without knowing more about their medical history. But having graft-versus-host disease can suppress the immune system, as can therapies such as ruxolitinib. What I tell patients is that precautions come down to just good common sense. Wearing a mask in certain situations is very appropriate. If you're going to go to church, often wearing a mask not only protects you from airborne respiratory illnesses circulating in the community, but it also signals to your friends and family that something's going on and that they should be more cautious around you, especially if they're feeling sick. Additional steps that can be taken in those situations include arriving late to church or leaving early, so you can sit in the back and minimize interactions.

(00:50:56): I typically tell my patients that when they're around close friends or family, people they know would be responsible enough to report symptoms of infection or concerns, that maybe in those scenarios one does not need to mask when they're in a small group of close friends or family where everyone is being honest as to whether they're sick or not.

(00:51:27): Beyond masks, just good hand washing. So, when we leave the house and come back in, it's really important to wash our hands. Certainly, before you eat and drink, it's important to wash your hands to prevent catching airborne illnesses.

(00:51:50): How long does one have to be careful? Well, that's a very complex question, and it really depends on prior history. Are you more prone? Have you already shown a propensity to develop these types of infections, or has your immune system so far been pretty good? Have you been free of these illnesses? And now that you're off immune suppression, I wouldn't say forego precautions, but be more educated and thoughtful when you need to take those special steps, like when you're traveling on an airplane, in an airport, or in crowds.

(00:52:31) What is ECP, extracorporeal photopheresis? How effective is this in treating GVHD of the skin, lungs, fascia, and joints?

(00:52:43) Dr. Amin Alousi: Extracorporeal photopheresis, or ECP for short, is a therapy that's been around since the mid to late-1990s. This is not a medication you take, but a therapy. Often, a patient needs a specialized catheter that connects to a machine that processes the blood and the cellular components involved in GVHD. It treats the blood cells, in very simple terms, and returns them to the body for processing. Extracorporeal photopheresis has been well reported in chronic GVHD, and some patients benefit from it.

(00:53:31): How likely one is to benefit depends on many factors about their GVHD, how many organs are involved, the different manifestations, and what prior therapies they had. But what I do think is important, if one is considering extracorporeal photopheresis, is that this is not a therapy that one would try for a week or a month. Often, if extracorporeal photopheresis is beneficial, we won't see results until about 3 to 4 months, and sometimes even up to 6 months, after the initiation of this therapy. And so if you're considering it, you really need to be committed to doing it for that period of time to see if it benefits you.

(00:54:13): Extracorporeal photopheresis is typically done twice weekly initially for the first couple of months, and then the sessions are spaced out. It usually requires living close to a center that offers this therapy. It's not something you would find at just any regular community hospital.

(00:54:37) This year, I've had nine ECP treatments. My dermatologist has suggested that I start narrowband UVB light treatments for skin GVHD. I'm currently on both treatments. Is there a way to determine which one is making the most difference?

(00:54:56) Dr. Amin Alousi: Yeah, so that's a great question and a question that first and foremost should be addressed with your dermatologist as well as your transplant physician. But I would say in general terms: "how do we know any therapy is benefiting a patient, and how do we know when a patient's on more than one therapy, which one is doing the trick? It sounds like this patient has been receiving extracorporeal photopheresis for an extended period, and narrowband UVB light therapy has been added.

(00:55:28): And so, in that situation, I would begin tapering down the therapy that, so far, has not been seen to benefit the patient. And one would start by spacing out the sessions. And so, if this patient is receiving therapy, let's say two treatments every other week, we would reduce it to two treatments a month and monitor for any signs that the GVHD is worsening with that tapering. And as I continue to taper down, at some point, I would typically stop the therapy and observe.

(00:56:06): It really comes down to trial and error and seeing if, when we taper the therapy, there's any indication that this is bringing on the symptoms or causing a hastening or worsening of the GVHD manifestation. And this applies to ECP or any other therapy: there may be situations where we add therapies, and in others it's more appropriate to stop therapies that aren't working. And that really gets down to a lot of specifics of your GVHD case that would be challenging without knowing you on a one-to-one basis.

(00:56:46) Is the new drug Niktimvo (axatilimab) effective in treating bronchiolitis obliterans syndrome?

(00:56:54) Dr. Amin Alousi: So, as I mentioned earlier, lung GVHD that we call bronchiolitis obliterans syndrome or BOS, can be a challenging manifestation of GVHD. In terms of how we assess response, first and foremost, when a patient has bronchiolitis obliterans syndrome and their lungs are compromised, we want to halt the progression. We really want to stop the lungs from getting worse. And that's one of the benefits of our interventions and therapies. It's really only a small subset of patients with BOS or lung GVHD who show improvement in lung function with any therapy.

(00:57:37): Niktimvo (axatilimab) has shown benefit in some patients, and in a very small subset, patients had actual improvement in their pulmonary function tests. The majority of patients had stability without further worsening. And so Niktimvo is a newer therapy of interest for lung GVHD, as are other therapies I mentioned earlier, like Rezurock (belumosudil) or Jakafi (ruxolitinib). And so, there is excitement. Our understanding of how lung GVHD occurs offers some hope that Niktimvo (axatilimab) may be a promising treatment for patients with this manifestation, but more research is needed to determine whether that's the case.

(00:58:32) You just mentioned Rezurock. Are there any other medications that specifically target chronic GVHD?

(00:58:40) Dr. Amin Alousi: At this time, four drugs are FDA-approved to treat patients with different stages of chronic GVHD. I’ll name them in the order in which they became approved by the Food and Drug Administration, and the indication for those, or the line of therapy. 

(00:50:00) The first drug approved by the FDA was Imbruvica (ibrutinib). This therapy was primarily studied in patients with early forms of chronic GVHD, and due to encouraging results in a prospective trial, led to the drug being approved for patients.

(00:59:21): The second drug approved by the FDA was Rezurock (belumosudil). That was a drug that was studied in patients with more advanced forms of chronic GVHD after failures of two or more lines of therapy. And even in patients with very severe manifestations in prospective trials, benefits were observed, including responses in patients with well-established chronic GVHD, multi-organ manifestations, and those who have failed other therapies. Despite that, a benefit was seen with the drug Rezurock. 

(01:00:13): The third drug approved by the FDA was Jakafi (ruxolitinib). Jakafi was studied in patients with chronic GVHD in a randomized trial in which half the patients received Jakafi and the other half received another standard treatment. Jakafi was found to be beneficial with a high response rate.

(01:00:34): And lastly, Niktimvo (axatilimab) is the newest drug approved by the FDA for chronic GVHD. And this was mainly studied in patients with advanced forms of GVHD, patients who failed many prior lines of therapy, and it showed very encouraging results.

(01:00:52): So yes, this is a new era of treatment for chronic GVHD. Thanks to well-conducted studies and participation in clinical trials, we've now been able to bring patients more therapies and offer benefits beyond just steroids.

(01:01:14) Are we any closer to finding a cure for GVHD?

(01:01:21) Dr. Amin Alousi: So, a cure would be challenging for chronic GVHD. Often, when an organ is scarred from the GVHD, be it the eyes with dry eyes, or the mouth with dry mouth, or skin thickening or sclerosis, it's hard to get resolution of that scarred tissue. I would say where we're making the most progress is in preventing both acute and chronic GVHD. And as I mentioned earlier, the likelihood of a patient developing graft-versus-host disease after transplant has gotten so much lower than it did just 20 years ago. About a quarter to 30% of patients now develop chronic GVHD, whereas once upon a time, that was closer to 50 to 60% of patients. And so while I would say a cure for patients who have chronic GVHD may be challenging, we're most encouraged that we will be able to prevent it in more and more patients. And so, I really believe that's where our greatest successes have been seen.

(01:02:38) Michala O'Brien: I'm afraid our time has run out for this evening. Thank you again to our expert panelists, Dr. Amin Alousi and Dr. Michelle Bishop, for sharing your expertise and time with us. And thank you, the audience, for your excellent questions.