Protect Your Health and Thrive after a Transplant Using Donor Cells (Allogeneic)

Transcription:

[00:01] Michaela O'Brien: Introduction.  Welcome to the workshop, Protect Your Health and Thrive After a Transplant Using Donor Cells. My name is Michaela O'Brien, and I will be your moderator this afternoon. Before we begin, I'd like to thank Sanofi, whose support help make this workshop possible.

[00:17] It's my pleasure to introduce today's speaker, Dr. Richard Newcomb. Dr. Newcomb is an attending physician in the hematopoietic cell transplantation and cellular therapy program at Mass General Brigham Cancer Institute and an assistant professor of medicine at Harvard Medical School. He serves as the co-clinical director of the stem cell transplantation and cellular therapy survivorship programs and medical director of hospital performance for the inpatient unit. Please join me today in welcoming Dr. Newcomb.

[00:52] Dr. Newcomb:  Overview of Talk. Thanks so much, Michaela, and thank you to everybody for spending time on your Saturday to attend this workshop. I think working with transplant survivors is something that brings me a great deal of joy, and I hope that this workshop you find useful.

[[01:28] I have a few learning objectives. I think the first is to explore the survivorship needs of those undergoing a transplant using donor cells. I'll refer to this interchangeably throughout the presentation as an allogeneic stem cell transplant. The idea is to open a discussion on how to thrive after allogeneic transplant and to discuss different survivorship care models that may be used either at your institution or at ours. Just generally, what are some things that I think are key components to take away looking after your health after a transplant?

[02:04] Survivorship matters because people are living longer and better lives. So I always kind of start talks on survivorship with this talk and this question, why does survivorship matter? I think everybody here has probably opinions on that, you know, and ones that may seem that this question is a little bit silly.

[02:22] Of course, of course it matters. The take home point is that so many more people are now living longer and better lives after an allogeneic transplant. Pictured here on the Y-axis is how more and more people have been living after stem cell transplant. What's presented here in this graph on the X-axis is time or years post-transplant on the Y-axis is probability of survival. You can see incremental improvement up the graph in the latest time period display, which is 2016 to 2021. The end story here is we're projected to have over 500,000 transplant survivors by 2030.

[03:18] Better pre-transplant treatments and regimens have led to better outcomes by several measures. Our transplant regimens are improved and safer, and we have better supportive care. If you ask me or any of my colleagues, at least in the clinical research space, what are we going to tell you is a good transplant outcome? Well, we need people to be alive. We'd like for them to be graft-versus-host disease free, and we'd like them to be living without any evidence of disease. So all of our drugs, our regimens, our clinical trials, this is kind of how we define what is a good transplant outcome. This is the bare minimum we need to reach in order to help people live well.

[04:12] There's graft-versus-host disease, chronic graft-versus-host disease, GVHD, it interacts with everything that I'm going to talk about and certainly is a super important topic. Survivorship is such a wide range of things. And I'm going to be focusing on survivorship domains, things that are important to you outside of graft-versus-host disease.

[04:33] It's just not going to be a focus on the things you're going to hear today. And I hope that you're able to attend many workshops in this symposium that are more focused on that, if that's your primary thing that is on your mind.

[04:45] Here are three cases of how survivorship can be improved after transplant. So I'm going to present some scenarios that motivated us at Mass General Brigham to start thinking about what we can do better for our people that are living after an allogeneic transplant.

[04:58] So these are three cases, a 73-year-old woman who was four years removed from transplant who falls and breaks her right hip. When we look back at it, we realize this person never had bone density screening for osteoporosis or low bone density post-transplant.

[05:14] Here's another one of a 62-year-old man who is seven years removed from transplant for leukemia, came in with a cough, and was ultimately diagnosed with stage four colon cancer. Screening colonoscopies had not resumed after transplant, so there was potentially a window that had been missed there.

[05:34] And then a 66-year-old with chronic graft-versus-host disease is admitted to the hospital with a heart attack, and the cardiovascular risk of his chronic GVHD had never been completely fully appreciated.

[05:45] So I'm going to share a quote from Julie Vanderklish and Areej El-Jawahri, who are two of my mentors. 

[05:51] Julie and I still co-direct our survivorship program and Areej is my research mentor, but they started our transplant program, our transplant survivorship program back in 2016. And I like this quote because what is the goal here? Our goal is to provide high quality survivorship care, conduct innovative research specific to transplant survivorship and improve the quality of life and care of transplant survivors, their families, and caregivers.

[06:17] So again, trying to move beyond just a live graft-versus-host disease-free, disease-free, because that's really, this is the bare minimum. We can do more to help our patients thrive.

[06:31] So the first section of this, I'm going to be defining and addressing some medical needs that I think are important that people know about.

[06:39] What are the things I need to know about to just stay healthy down the road?

[06:42] I just got through this whole transplant thing. I'm in remission. My transplant doctor says, hey, you're good to go from a survivorship perspective. What do you need to be aware of? The good news is that the field is really thinking about this.

[06:56] Recently updated guidelines for screening and preventive practices are now available. Three years ago, our major transplant societies, ASTCT and EBMT, came together and updated for the first time in over a decade, survivorship guidelines for screening and preventative practices. So everything I'm going to present here is sort of in accordance with these concurrently published guideline recommendations. At first glance, this feels overwhelming, or at least it can, because truthfully, the transplant treatment journey, it can impact the whole body.

[07:33] We want to care about your heart health, lung health, bone health, what your thyroid and reproductive hormones are doing. These are things that are very important to be monitoring for lower levels of hormones post-transplant.

[07:52] Infection risk and second cancer screenings are important.  We know that patients, even when they're off immune suppression, and especially if you're on treatment for things like chronic graft-versus, to host disease, infection risk is something that still persists. It doesn't just end after day 100 after transplant when the restrictions are lifted.

[08:12] And then finally, second cancer screenings. So we know that any patient with cancer, once they've gone through that, or anybody who's gone through a transplant, say you didn't even go through transplant for a cancer-specific condition, we know that patients after allogeneic transplant are at higher risk of developing other types of And so having an awareness of these things is helpful.

[08:36] So as you can imagine, this is quite a lot. And I'm not going to be able to talk about everything, but I hope I'm going to outline an approach that we think about as clinicians.

[08:46] And I hope that that helps you think about how you can think about your own health.

[08:51] The first focus here is going to be on heart health. In truth, as our graft-versus-host disease prevention regimens have gotten better, cardiovascular health, I would maintain, is probably the most important aspect here for survivors in 2026. I think that cardiovascular health is super essential to maintaining long-term well-being.

[09:16] I'm going to go through a couple different reasons for that and then give you a framework to think about how you can approach any survivorship topic. So the first is just defining what are the late effects, what contributes to that risk and how can I identify things with screening tests ahead of time? What are the best things that we can do to maintain your heart health?

[09:43] If you go back to those cases I started with, we want to prevent things like heart attack and stroke or irregular heart rhythms as best we can because we know increasingly these are things that are actually a threat to our patients even after they've survived their transplant and their cancer journey.

[10:01] So I'm going to go through this framework in detail with heart health, and then I'll kind of outline some of the other really important topics for health from a medical perspective for you.

[10:11] Transplants impact heart health in several ways. How is heart health impacted post-transplant? Many of our patients, after an initial weight loss through the first three to six months, first 100 days to 180 days post-transplant, many patients will start to gain weight. Then when they return to their pre-transplant weight, often weight gain happens after transplant.

[10:33] There's a variety of reasons for that. I try to tell my patients it's a normal thing. We've just given you an immune system from somebody else. Like there's a lot of changes going on in your body and food and the way that you process food likely changes after transplant for a variety of reasons. So weight gain is a very normal thing post-transplant, especially folks who have changes to their hormone balances and their hormone levels.

[11:00] There's increased risk of high blood pressure and diabetes. Some of that is related to medicines we give, whether that's prevention of graft-versus-host disease or treatment of graft-versus-host disease. Medicines like steroids and tacrolimus, cyclosporine can wreak havoc on different parts of your cardiovascular system. Some of this is also knowing what can we control and what can we not control? Sometimes you need to be on medicines that will put your heart at risk, and we need to know how to manage that.

[11:33] Increased risk of heart disease, which I'll define as coronary artery disease or blockages or plaques in the blood vessels that lead to the heart and increased risk of stroke. There are many things that contribute to this, and you can apply this framework to any type of medical issue post-transplant.

[11:51] Each patient may have unique cardiac health risks after transplant. One reason I love survivorship care so much is that from a medical perspective, everybody is a little bit different. You're going to have your own things that are specific to you that come to the table and can contribute to cardiovascular health. That might be age. It might be prior smoking or how much you exercise or what was your blood pressure before transplant, your cholesterol. Do you have heart disease currently or is there heart disease in your family at what age? These are all things that existed inside you before you even had, say, leukemia or before you went through a transplant.

[12:27] Transplant regimens can increase cardiac complications post-transplant. There are things related to the transplant regimen or the cancer treatments that you got. There are medicines that can affect the heart more than others, things like anthracyclines that are commonly given in the treatment of leukemia or prior radiation Finally, transplant-specific regimens, whether what medicines were used when you were hospitalized or that initial acute phase of transplant. Graft-versus-host disease also serves as an increased risk of cardiovascular disease. Everybody has different aspects of these three circles that contribute to how important is heart health to you.

[13:08] Understanding these things is really helpful because if you can put these different parts of the puzzle together, you can then figure out, well, what do I need to know. Ultimately, in survivorship, knowledge by itself is insufficient. We want to do something to kind of help you live better. How strongly we recommend things will somewhat be in part due to what is the underlying risk. So this is the good news. This applies to any of the overwhelming medical topics in survivorship; we have ways to help you.

[13:41] Optimal survivorship depends on more than medicine. Sometimes it's blood tests to understand what is your cholesterol and how can we manage that? Is there any evidence of prediabetes or diabetes? These are things that we can check, including your thyroid level, which can impact your heart level, your heart health.

[13:59] I always spend a good amount of my time trying to talk to patients that it's not just medicine is the only answer here to living well post-transplant. In fact, one of the most common things I hear from survivors in my clinic is I just went through all this. The last thing I want is to add another medicine, and many people are right.

[14:18] Diet, exercise and medications are important in survivorship. With diet and exercise alone, there's no one right diet after transplant. I generally recommend a well-balanced diet, a Mediterranean diet that is, you know, low on carbohydrates, high in proteins that come from things like fish, vegetables, or white meats like chicken, and plenty of fruit and vegetables to round that out.

[14:44] There's not one absolute right diet that's going to guarantee your health. The idea is you want something very well balanced, one that's not going to promote weight gain, and one that you're going to feel happy with.

[14:59] Exercise can mean so many different things. I think one of the things I always talk with people about is if you look at communities around the world about where people are healthy and live long lives, it turns out those communities are located in places like on the top of the hill where people have to walk a lot.

[15:16] They just implement exercise like walking, gardening, being out and seeing other people in the daily parts of their life. I try to redefine exercise for folks because exercise can sometimes make people think I have to go to the gym for 30 minutes like every day. The truth is, is being active and living an active lifestyle is much more important than just getting a certain amount of exercise a day. You have to do something that's going to feel fulfilling.

[15:46] With these two things alone, if you're doing these things regularly and you're keeping mind on these things, and there will be more workshops in this symposium to help you with this, because this is really a theme throughout all of survivorship. That alone is going to, you're already going to be well, well ahead and keeping tabs of your heart health.

[16:06] Medications can also help in survivorship. I always tell people sometimes medicines help. We have medicines to help lower cholesterol. We have medicines to help with blood sugar. We have medicines now actually to promote weight loss. These are all things that sometimes we have to implement to keep you healthy.

[16:22] This framework can help assess post-transplant risks and identify healthy actions to take for lung health, bone health and infection risks. So I hope that this framework kind of helps you kind of think about, well, what is the risk? How would that actually impact my life? What are the things that contribute to it and then what can we do about it?  That framework goes across all aspects of medical needs of survivorship.

[16:38] It has to do with your lung health and how we can use breathing tests to monitor for things like chronic graft-versus-host disease in your lungs, because it's essential that we detect those things early and start medical treatment.

[16:49] It's essential for bone health and preventing fractures to do bone density tests post-transplant, because we have good medicines and we can promote healthy lifestyle things like weight-bearing exercise to help protect your bones.

[17:01] It's great to screen for things like thyroid deficiency and reproductive hormone deficiencies, because for some people, hormone replacement is really, really important, especially for our young transplant survivors who may have early menopause with things like total body irradiation.

[17:18] Infections, we have to be on the lookout for, and everybody's a little bit different because truthfully, everybody's on different medicines and everybody's immune system comes in at different times a little bit.

[17:28] Transplant's a little unpredictable in that way.

[17:31] And so maintaining vigilance for that and knowing that sometimes we have to do things like antibody replacement with things like IVIG, and we do vaccinations as part of this routine practice of trying to prevent the burden of infection on you.

[17:45] Cancer screenings are also important in survivorship. Skin checks and dental exams are especially important. Every cancer survivor is individual and brings different things to the table in terms of their age, their family, risk of different cancers. But that's why we have to think about these things so that you can have a plan that really works for you.

[18:05] I will also say and make a plug for something I tell all my cancer survivors that skin checks and going to the dentist are actually a really important part of preventing second cancers post-transplant.

[18:16] People always get a little confused when I tell them, well, when you have somebody look at your skin, that's actually probably the most important cancer screen that you can do because that is the most common. Skin cancers are the most common second cancers that can happen after transplant.

[18:31] There are other areas of the body that we need to pay attention like the kidneys, the liver, brain health, dental health and eye health. So the list here goes longer in terms of the things that can be impacted post-transplant.

[18:45] I'm not going to have the time to go through everything, but I'll kind of wrap up this session with a couple different cases just to show you that transplant survivor planning is really an art.

[18:57] Every patient deserves a personalized, feasible, survivorship plan. This plan should incorporate your age, your prior medical history, your cancer and transplant treatments, whether you're actively dealing with graft-versus-host disease now or that was something that happened in the past, and what your family history is in terms of the things that you might be at risk for moving forward in the future.

[19:19] The following case studies illustrate how different patients need different survivorship plans.

[19:23] This is a 32-year-old woman who had leukemia after transplant involving total body irradiation. So as a survivorship clinician, when I see this person in clinic, I'm already geared to thinking towards specific things that are going to be super important for this young woman. Cardiovascular health, as I mentioned, assessment for premature menopause or early menopause and need for things like estrogen therapy. Monitoring lung health long-term because radiation can impact the lungs. Bone density is very linked to the hormone health and knowing somebody's bone health. And then transplants that incorporate radiation, we know we have to be on the lookout for second cancers. So this would be what my survivorship plan would be geared toward for this person.

[20:11] It's a little different for a 78-year-old man with myelodysplastic syndrome after a reduced intensity transplant. Here, I'm still going to be caring about heart health. I mentioned that's probably the most important thing. But I'm going to be a little more attuned to things like how's that person's cognition? And I really want to make sure I'm assessing fall risks and understanding what that person's bone density is like to try to prevent falls. And I'm going to be really kind of keen on things like vision changes because that might really impact this person's life in a particular way. So like I said, everybody is a little bit different, but everybody deserves a personalized plan.

[20:49] So my takeaways from this part of the talk for you are that late effects can impact every organ system. As we improve graft-versus-host disease prevention, the medical focus of transplant survivorship should prioritize heart health. You deserve a personalized medical plan to help you thrive.

[21:05] Survivorship plans should help coordinate care with primary care doctors. When you get those survivorship care plans, I would hope that they help you in terms of working with your primary care doctors or working with your family or other people in your team so that you know what are the things that you can take moving forward.

[21:20] Of course, medical needs are not the only thing that are important in the transplant survivor experience. I'm going to include here on this next slide, This treatment journey is going to impact your daily life in many different ways and sometimes it has to do with mood.

[21:35] Many of my transplant survivors have depression, anxiety, and symptoms of trauma related to this experience. I can't tell you how many times people have told me, you know, I started to have some night sweats and that was just really traumatizing. It ended up not being related to my history of lymphoma. But gosh, that was a lot to even think that my cancer could be back.

Survival [21:59] Fatigue, sexual problems, and sleep disturbances are common after transplant. Everybody's sexual health gets impacted post-transplant, and we don't do a good job talking about it we have some talks on intimacy here in this session and my hope is that you're you know you're able to learn from that and learn how normal it is that sexual health is impacted post-transplant.  Some people are able to go back to work others can't go back to work in the way that they want to fatigue is omnipresent i think fatigue i honestly the two most common things So I feel like we either don't ask about, which would be sexual health, or we do ask about but don't know what to do about, which is fatigue, is very, very common.

[22:38] And this persists for months after transplant. It can really catch some people by surprise. Sleep disturbances are extremely common, and as I alluded to, fear of recurrence.

[22:48] So, you know, just to go back to that initial slide that I gave you, you can very easily see this is not just about being GVHD-free or relapse-free. Your journey is going to be unique to you, and you may or may not experience any of these things. But it's important that we as a transplant community understand that this is really important to our transplant survivors.

[23:11] Sexual health challenges can often be addressed successfully, So I'm going to focus a little bit on sexual health because, again, I just feel like it's a topic just as an introduction, and it's a topic that we often don't ask our patients about in clinic.

[23:21] It’s super important because it's associated with people's quality of life, their experience, and their own well-being post-transplant. So like I said, it's extremely common. Up to three-quarters of people will report some type of sexual health matter post-transplant.

[23:40] This is not a thing that people will volunteer and ask about. It reduces people's experience. It increases mood symptoms like depression and anxiety. But a lot of these issues are addressable.

[23:52] For men, sometimes it's as simple as the testosterone is low, post-transplant it needs to be replaced, or there are medicines contributing to erectile dysfunction, or erectile dysfunction as a part of aging has been accelerated, but we can use medicines to address that.

[24:11] For women, it can be something like vaginal atrophy, causing dryness or pain during sex. That can be related to graft-versus-host disease, or it can be independent of that as people are dealing either with lower estrogen states or just, again, acceleration of aging processes. The good news is that we can address those things, too. We just need to know about them, and we have to ask about them. That's on us as clinicians.

[24:38] Mood disorders and medications impact and can accelerate sexual health concerns and lead to things like loss of libido and loss of intimacy. I've, in my experience, have found that gynecology and urology can be super helpful.

[24:51] We also have our own transplant sexual health practice within our group where we have a couple of clinicians who are BMT clinicians that specialize in these things. We've made specific interventions to help people return to sexual well-being.

[25:04] It's honestly one of the most powerful things that we do because I think it gives people back a part of their life that they thought maybe was gone. So I hope that this gives you a message of hope that like to say, if you're having these concerns, bring them to your clinicians. My hope is that they can help you.

[25:21] Fatigue is also a common posttransplant challenge but one that can also be addressed. The second challenge that I want to talk about is fatigue. It is really, really common in people's experience. I probably don't need to tell you guys this. You guys know this as you go through daily life.

[25:33] But I hear it all the time from my patients at six months, 12 months, two years, et cetera, even longer post-transplant about how I just can't do the things that I want to do or I have to take a nap, and that's frustrating to me. Fatigue can also be just a very, very hard thing medically to wrap our minds around, as the causes of fatigue are a lot, right? But we know that this fatigue, it lingers, it's bothersome. It worsens the patient experience. It increases mental distress.

[26:07] The good news is it's actually also completely addressable. A lot of times people think that that's something they have to live with or something's wrong with them because of how tired they are all the time. So the way that I approach fatigue in my survivorship clinic is just taking the time to understand it and kind of go back to that framework of what are the things medically that could be causing it? Is there active chronic GVHD that I need to be addressing? Or is actually the fatigue a side effect of the medicines that I'm using to treat, say, blood pressure? Beta blockers are very common causes of fatigue. Or is it a side effect of the medicines I'm using to treat chronic GVHD? are those medicines actually addressable?

[26:50] I think we'd be thinking in medicine often we want to just add medicines. But sometimes we actually need to change and tailor those medicines to make sure that we're addressing things like fatigue if we can.

[27:03] Exercise can actually help with fatigue.  The other thing that we've found in our practice here is that counterintuitively structured exercise programs are extremely helpful to help people's fatigue. They're hard at first, but as you address deconditioning that's normal with transplant, we tell you isolate for 100 days or sometimes longer. We take people out of their routines, whether it's like going to the gym or We're seeing other people and doing group things to stay physically active. As we take people away from those things, deconditioning is a normal part of the process.

[27:38] Helping people get back into the activity that gives them meaning and gives them energy is actually super, super helpful. It's a very, very important part of fatigue to help people work through that.

[27:51] Mental health issues also need to be addressed. Often there's a way that we need to find ways to address mental health because mental health issues like depression, anxiety, or other mood disorders can really, really impact fatigue. Identifying those, getting people in, at least we have a social worker in our program, and I know many programs do, and many cancer institutes now have a mental health component to the services that they offer both their patients and their survivors Addressing these, understanding them is challenging, but my end message to you is that actually I think it's completely possible. These issues can be addressed as long as we recognize them, and we know what to do about them.

[28:41] Survivorship consults should be tailored to each individual patient. I try to lead this with almost any survivorship consult that I do for people. I say, well, I'm going to talk a lot about your own experience. I'm going to talk a lot about the medical needs that I think are most relevant to you. We're going to talk about how you, lifestyle, medicines, and transplant interact with all this. One of the key takeaways that I want for you guys to have is that you don't have to navigate this journey alone. Your transplant team is there for you. I think the approach that we take at Mass General Brigham is that, you know, if we put somebody through a transplant, we want to help people thrive after it. That's why we start survivorship planning at day 100.

[29:28] Survivorship plans should begin right after transplant and cover lots of issues. After transplant, we start it early. We start to try to screen for things on the medical side. We ask questions on the survivorship experience side early. We try to do a consult for everybody at one year so that everybody gets a document that I call a survivorship care plan. That care plan identifies what are the treatments you've been through? What are the active transplant and cancer things that you've been through? Then how do we take all that in and sort of make a plan that's right for you, both on the medical side and for the things that you're experiencing on a day-to-day basis that we can improve?

[30:06] It goes to their primary transplant team, and it goes to their primary care doctor if they have one. If they don't have a primary care doctor, we try to set them up for it. We think that doing this within the first year of transplant helps people set up for success down the road, because I know that if we leave this to people and just say, you have to figure it out, this is a full-time job.

[30:28] You have to learn all these things about your body, and you have to learn all these things that you're experiencing and how to figure it out for yourself. I think that as a transplant community, this is something that we should be taking on and taking pride in. Fortunately, there's also really great resources for you guys like BMT InfoNet.

[30:46] I send my patients to BMT InfoNet all the time because almost all these topics we've talked about today, there's good content on the website and there are going to be workshops here at this symposium that will highlight the importance of all those things. So again, you don't have to do this alone. This is complicated, but you should have people to help you alongside the journey.

[31:11] Now, I think there's part of this of like, we've talked about some of these tools and how to thrive after transplant, exercise, diet, avoiding sunburn, finding the people around you that are going to support you and taking care of your mental health.

[31:28] I have a patient, if you guys are sticking through the symposium on, who's going to give a video on Thursday.  She talks about transplant as sort of learning how to dance and actually wrote a children's book about it. The idea is that everybody is going to learn the rhythm of their dance post-transplant in their own way. There's not one right way to thrive after transplant and everybody will take things as they come.  

[31:56] I would encourage each of you to think about what brings you joy and the things that bring you joy. Structure your life around that. In my personal experience, those are the folks that really learn how to thrive after transplant. They can take the tools that mean something to them to improve both their physical and their mental well-being. I've been alluding to this throughout my talk, but again, I strongly believe that transplant programs need to support survivorship. I'm a little biased. It's what I do, but I think it's really important because, like I've mentioned several times, this is a complicated process, and leaving people by themselves is difficult. As you can imagine, there's not one right model or one wrong model.

[32:48] This is a graph that accompanied the publication of the most recent survivorship programs. This is kind of people moving across time from getting transplanted and transitioning back to the community. There is this overlap period of when you're sick and need treatment and things are high risk from a transplant perspective that the transplant program is predominantly involved.

[33:16] But it's somewhere along the line and people get better and you get past those windows of GVHD, past those windows of relapse, out of those active windows of transplant, the primary care community-based team becomes more important.

[33:34] We shift from thinking about sick and treatment to healthy and prevention, which have been a lot of the things we've talked about here today. The key issue in survivorship is always just like, who is the medical team that is the taking ownership or taking, you know, is your steward throughout this process? There are many different models at different centers where that's still entirely owned by the transplant team. It's owned by specialists within the transplant center. It's owned by embedded survivorship care within a transplant center or a cancer institute, or it all just lives based in the community.

[34:15] You can imagine there's many different factors that go into which model works best for a particular transplant program or a particular cancer center, based on what part of the country they're in and what's their catchment area and where their patients come from and how many patients they have. I do think one thing that's clear is that if you survey transplant clinicians, they prefer to own survivorship care and if you survey transplant survivors, you want your team's input. Like you don't, you feel like you've just been through this whole thing. I don't want to start new meds or do new screenings unless my transplant team is really involved in that.

[34:53] That’s why we really believe in this ownership model of starting transplant survivorship early, of embedding it within the transplant team so that we get these critical screenings started early. That’s the kind of our approach that we do at MGB to make sure we're not missing heart screenings and having people with heart attacks down the road that we feel like we could have prevented, that we're looking at bone density.

[35:19] A good survivorship plan has many dimensions, We're providing really good graft-versus-host disease education so that you know what chronic graft-versus-host disease looks like. We're asking about sexual health so that you know that it's important and it's a common thing that we can help with. That's why we deliver survivorship care plans, because these need to be individualized. They need to be personal to you. They need to highlight your priorities and serve as a gateway back to the community. This next slide is sort of a summary of the things that we do at the Mass General Brigham to kind of promote survivorship care. Again, I want to emphasize there's not one size that fits all, but I think early integrated delivering information and education to you so that you can take it back both to yourself, your family, but also to the doctors in the community that may be caring for you.

[36:15] So in conclusion, transplant patients and clinicians derive a lot of meaning and benefit from formal survivorship efforts. Your transplant team is there to help you thrive after your treatment is done. Survivorship care plans can really help you focus on your health. Healthy lifestyle choices can help you thrive.

[36:34] Sometimes we need medicines to help you, but how you live is like the most important thing after transplant. Each one of you as survivors, you are an inspiration. As we partner with you guys, that's that the partnership is really going to be the thing that improves survivorship care.

[36:51] So I want to thank BMT InfoNet. I want to thank everybody that's here for spending time on a Saturday with me talking about heart health and survivorship programs and your care plans, and I'd be happy to take any questions at this time.

[37:08] Michaela O'Brien: Q & A: Thank you, Dr. Newcomb, for this excellent presentation. Let's go to some questions. If you do have a question for Dr. Newcomb, please use the question box on the lower left side of the screen. We will answer as many questions as possible.

[37:25] I am a male who had an allogeneic transplant two years ago. You mentioned bone density. Is bone density an issue for guys too?

[37:34] Dr. Newcomb: It's a really good question. It is, actually. I think it's not as common as in women. I think women are higher risk for osteoporosis or lower bone density across the board. So I think it's something that we often think about a little bit more with women post-transplant in the survivorship space.

[37:56] But I routinely screen all my male survivors at some point in the first-year post-transplant for osteoporosis or low bone density. There's a couple of different reasons for that. One, many cancer treatment regimens incorporate steroids and steroids are an equal offender and will decrease bone density in men and women.

[38:18] Two, steroids are an important part sometimes of graft-versus-host disease treatment. And then men can sometimes also have osteoporosis independent of all these things. And we know as you put people through chemotherapy, whether that be chemotherapy or conditioning therapies like radiation, that that can have an impact on bones too.

[38:37] So I recommend for both men and women post-transplant at least once to have a bone density test. And that bone density shows either osteopenia, which is kind of sort of weak bones, or osteoporosis, which is low bone density, that plans be made to address that.

[37:08] Michaela O'Brien: As a survivor, are there precautions I can take to prevent secondary cancers?

[39:05] Dr. Newcomb. It's a great question. I think part of the reason that we do what we do is to educate people about what are the screenings that you need. And everybody's a little bit different. I think it somewhat depends on what your age is. Are there hereditary factors? So I think the most important thing from a medical perspective is identifying what are the screenings you need to return to or start, right? So for say a person who's 45, those conversations are like, hey, it's time to start colon cancer screening.

[39:38] For women who've had total body irradiation or anything as part of their transplant conditioning, it's talking about starting breast cancer screening earlier and being more aggressive and incorporating things like breast MRIs into that screening regimen or portfolio. I think that the most important thing is trying to figure out everybody's a little bit different. So it's hard to say what's there's no one right screening regimen.

[40:05] It's just a matter of taking into account who you are, what your transplant regimen was, and what is your cancer history and what is behind that cancer history to make the best screening regimen for you.

[40:19] Outside of that, the lifestyle factors that are under your control, you know, I think these studies about diet and studies about exercise, there's, it's really hard to get to the bottom of, is there one exercise regimen or one diet regimen that prevents, that prevents cancer? And the truth is we don't, we don't really know. And so when I'm talking to people about what are the lifestyle choices that you can make, whether it be exercise, maintaining sleep, or eating well. I try to encourage those things independent of prevention of other cancers, because the truth is we don't really know how those things completely interact.

[41:02] But we know that exercise is a good thing and eating healthy is a good thing. So I try to encourage those things independent of preventing cancer risk. 

[41:17] Michaela O'Brien: I'm a female one-year post-transplant with osteoporosis. Is estrogen replacement enough or do I need another treatment?

[41:25] Dr. Newcomb: It's a great question. So I can tell you what my approach to that is and speaking with our endocrinologists. If someone is, say, young and newly into a new onset menopause after transplant, and it's the first time it's been found, I will generally just start hormone replacement and then see how bone density looks a year later. Often, especially for young people, hormone replacement alone is sufficient to restore bone density.

[42:05] And you wouldn't want to necessarily jump to medications for osteoporosis unless you really had to. So my approach for young people is hormone replacement and then figure things out down the road. Maybe there's need for osteoporosis management, but you first have to get the hormone balance in place. We don't have a total sense to know what's the right age that you should stop doing that.

[42:36] I think the field of hormone replacement has actually changed a lot since I was in medical school. When I was in medical school, there was the teaching that we don't replace estrogen for women above a certain age. And the cap of that age is a moving target. So in general, my approach is to say, if you're in menopause before an age at which we would predict that hormone replacement is the best thing to do before jumping to osteoporosis management. If you're at an age at which menopause would be expected or about to be expected, I then sort of move more away from hormone replacement and just managing the bone density issue by itself.

[43:17] Michaela O'Brien: Okay. This is a follow-up to osteoporosis. What about a Reclast infusion?

[43:24] Dr. Newcomb. Yeah, Reclast infusion. I'm a big fan of Reclast infusion. So I think bisphosphonates are really, really important drugs for management of osteoporosis. Again, provided you're in the right age group, that your kidneys are okay, that people have talked to you about risks associated with bisphosphonates, any medicines associated with risks.

[43:48] But we use it frequently at our center and our endocrinologists that live outside the Cancer Institute, but with whom we collaborate. Bisphosphonates are usually the preferred treatment of choice. I like the infusions because it's once yearly. And a lot of our patients struggle with the pill or because you can also take a pill once a week, but that pill can be associated with GI side effects that truthfully, I find in our patients are a little bit augmented. So I would rather do the infusion.

[44:22] You know, I tell all my patients before they have a bisphosphonate, they should be, they should go to the dentist and address any dental work before starting the bisphosphonate. And it's really important to make sure somebody's vitamin D is at an adequate level before you start bisphosphonates, but they're generally fairly well-tolerated and I think are an important part of post-transplant bone management.

[44:44] Michaela O'Brien: How routinely should the screening for thyroid, testosterone, et cetera, be done post-transplant?

[44:51] Dr. Newcomb. t's a great question. I think, again, everybody can be a little bit different.  I can tell you what we do is we try to check it at least once within the first-year post-transplant. And then if it's okay as long as people aren't having symptoms related to testosterone deficiency or hypothyroidism. I usually don't check it again for another year.

[45:12] But obviously, if there are issues that we find that people are deficient and need replacement, then we check things a little more often as we get people onto replacement therapy.

[45:25] Michaela O'Brien: At what age should you start breast cancer screening? I had total body radiation at 30 post-allo transplant currently.

[45:37] Dr. Newcomb: The guidelines recommend starting usually within five to seven years after the receipt of total body radiation or the age of 40, whichever one comes first. So it's not something you need to start immediately after. And again, personal factors can matter here, right? Like somebody with a family history of breast cancer, you might start much sooner.

[46:04] But assuming that there isn't a concerning family history or there's no known things like BRCA mutations or other inherited things that can cause breast cancer, if we're just dealing with the total body irradiation as the main risk, I usually start that within five to seven years of transplant.

[46.27] Michaela O’Brien: This person received an allogeneic bone marrow transplant almost two years ago. They're still dealing with chronic fatigue. What type of entry-level exercise programs do you recommend, and how often should they do this?

[46:43] Dr. Newcomb: It's a really good question. I think the first thing I would recommend here is to talk, whichever you're dealing mostly with your primary care doctor at this point or your transplant clinician is sometimes just referrals to physical therapy for a structured exercise program.

[47:03] It's hard to tell without doing an assessment of somebody's conditioning and where they're at from a muscle perspective and knowing kind of where they're at to recommend any particular type of regimen. But I think physical therapy and working with physical therapy colleagues can be hugely, hugely helpful in terms of that.

[47:24] The other resource that I tell patients and that tends to be, it's nice because it's a national resource, is that the YMCA partners with Livestrong and YMCA memberships are fairly, I guess when it comes to gym memberships are on the fairly affordable side.

[47:39] But with the Livestrong program, with YMCA, often people will, this kind of depends YMCA center to YMCA center, but a lot of the centers will actually offer a couple free sessions working with a personal trainer to put together an exercise plan that works for you and your body based on what you can do.

[47:58] Because the last thing you want to do is just enter a random structured exercise program that's not tailored to you, your body, and your needs.

[48:07] So those are just a couple suggestions, one, through the medical route and a referral, and two, through cancer survivorship programs like Live Strong and the way that they partner with associations like the YMCA.

[48:22] Michaela O’Brien:  This person is asking about GVHD. I know you mentioned that there's going to be other workshops focusing on that, but this is a general question. Is GVHD always a concern, and does it stop being a possibility at some point after transplant?

[48:45] Dr. Newcomb: I think the time we worry most about the occurrence of graft-versus-host disease is in the first two years post-transplant. It's a little different depending on what type of prevention regimen was used. You know, I think increasingly more and more people are getting something called post-transplant cyclophosphamide as their predominant graft-versus-host-disease prevention regimens. That's high-dose chemo after you get your cells.

[49:12] And I've found that the onset of GVHD sometimes can be a little bit later beyond the one-year mark, I think. So I think I usually tell people if it's going to pop up, it tends to pop up in the first two years, though it can happen later. And like anything in transplant, whether that's the disease coming back, that's called relapse or graft-versus-host disease happening, the more years you put together, the less likely it is that you're going to be dealing with it down the road.

[49:41] There are some things that will almost always trigger graft-versus-host disease to happen. So if you spend a whole summer out in the sun getting tan and sunburned, the likelihood is that we will be dealing with graft-versus-host disease, whether you're one year out, two years out, or 10 years out.

[49:58] Just because if you give your donor immune system something to get worked up about, then we can see graft-versus-host disease. Similarly, in patients that have a second cancer and required any site of radiation, sites of radiation can always lead to graft-versus-host disease even several years out. So it's always a little bit different for each person. The general principle is the more time you go without it, the better. There are things that can always trigger graft-versus-host disease that we try to be on the lookout for.

[50:35] Michaela O’Brien:  We have a couple questions about finding physicians after their transplant. This person doesn't live near their transplant center. What's the best way, in your opinion, to find a doctor in town? And what should I be asking them about my treatment and moving forward?

[50:55] Dr. Newcomb: So, every transplant center is a little bit different. I think what I would encourage you to do is if you can still have access to your transplant center is to ask for a survivorship care plan because that way they can summarize for you in one neat document.

[51:12] What are the treatments you got for the underlying condition that led to the transplant? What was the transplant regimen and what were the known complications like graft-versus-host disease, and then what would they recommend for your health moving forward. I think that's a really important part of survivorship care.

[51:31] And if you receive that document, what that helps you to do is it takes the pressure off of you having to explain everything to a new clinician. Because the reality is there are many parts of the country where there is no transplant clinician nearby, right?

[51:47] And so if you have a care plan that you can take to your primary care doctor, that will help them understand your health and also the things that they need to look out for from a medical perspective. So that would be the first thing that I'd recommend to you to do.

[52:03] The second thing is if that's not an option for you, it's connecting your current clinician with resources that could be helpful. That could be even as simple as referring to things like BMT InfoNet or having them try to reach out to your primary transplant center. Partnership is key, and having a care plan is really the thing that can help you help your current community clinicians take good care of you.

[52:40] Michaela O’Brien: This person's asking, does your family history or genetic history change after transplant because of an unrelated donor?

[52:50] Dr. Newcomb: It's a complicated answer. So after transplant, your body is still you, But your blood belongs to the donor, right? So let's take, for example, say you went into transplant and you have a hereditary risk of breast cancer. So you inherited a risk of breast cancer from one of your parents. After transplant, that risk is still there, right?

[53:27] Now let's take a different scenario. You had leukemia. You get the transplant. And now your blood, you know, let's say your leukemia is carried, your blood should be all donor. Unrelated donors don't have, there's no mandatory requirement for unrelated donors to have genetic screening for risk of leukemia, right?

[53:52] So there are times that happen that people get donor-derived leukemias. It's rare. It's not common. We try to use young, healthy donors that don't have blood count issues at the time of screening. But we don't know what the best screening is for donors.

[54:08] And there's active work in this field from people across the spectrum to try to say, how can we best put transplant recipients in the best possible position by making sure that we're doing adequate donor screenings? So I think that field will evolve in the next five to 10 years to try to reduce risks of donor-derived cancers. So it is possible, but it is unlikely. Like most patients that receive an unrelated donor will not have an issue that's related to blood.

[54:44] Michaela O’Brien This will have to be our last question. We are running out of time. I had an allogeneic transplant nine years ago, and my eyes were affected. But I have bronchioles that are scarred, which affects my breathing when I do heavy lifting, per se. Will the condition keep getting worse over time, or are there things I can do to improve my lungs?

[55:10] Dr. Newcomb: That's a good question. First, congrats on being nine years out. And second, I'm sorry to hear that there's scarring in your lungs. That's likely related to what sounds like graft-versus-host disease or potentially an effect of conditioning therapy.

[55:27] So I think the most important thing with not everything I talked about, like, is about medicines and medical management, but bronchiolitis obliterans or chronic graft-versus-host disease at the lungs is one that has to be really closely managed.

[55:43] So my hope is that you are still being seen at a transplant center with somebody who has expertise in graft-versus-host disease who can manage the bronchiolitis obliterans. Michaela, I can't remember if we have a bronchiolitis obliterans session at this symposium that could be helpful, but we certainly have material on it on BMT InfoNet.

[56:10] But it's really important to medically manage that as best as possible because it's the medicines that sort of prevent things.

[56:17] The other thing I tell my patients with bronchiolitis obliterans is to try to avoid recurrent respiratory infections because things like respiratory infections will trigger the bronchiolitis obliterans to get worse. And so trying to stay healthy, trying to stay away from people that are sick and doing the activity that you can do. Involvement of the lungs of graft-versus-host disease is one of the more challenging ones because it makes the lifestyle things that I've talked about in this session harder.

[56:50] But it's, again, goes back to trying to find that right balance for you. What's the physical activity that you can do and the things that you find meaningful?

[56:59] And if you're not able to do those, talking to your team early about that because maybe changes to your medication regimen are needed.

Moderator:

[57:10] Michaela O’Brien: Closing. On behalf of BMT InfoNet and our partners, I'd like to thank Dr. Newcomb today for a very helpful presentation. And thank you to the audience for your excellent questions.