Living Well after Treatment: Coping with Fatigue

  Download Speaker Slides  

Living Well after Treatment: Coping with Fatigue

Presenter:  Erin Costanzo, PhD, Professor, Department of Psychiatry, University of Wisconsin School of Medicine and Public Health

Presentation is 37 minutes long, followed by 18 minutes of Q&A

Summary:  Many patients experience significant fatigue for months or years after a stem cell transplant or CAR T-cell therapy. Learn a variety of strategies you can try to manage chronic fatigue and lessen its impact on your daily activities.

Key Points:

• Tell your doctor if you are having ongoing or new chronic fatigue. Some medical causes of fatigue are easy to test for and treat.
• Creating an energy budget and daily schedule can help reduce the effects of chronic fatigue on daily  life. Decide which activities are most important to do, schedule them for times during the day when your energy is highest, and build in rest breaks.
• Moderate physical activity is one of the best treatments for chronic fatigue. Using a smartwatch or an inexpensive step-count pedometer is an easy way to track your activity.

Highlights:

(02:01): Fatigue is normal and expected after transplant and CAR T-cell therapy and can linger for mant years.

(08:50): Resting too much and lack of activity can make fatigue worse.

(09:51): Pacing yourself is important. Trying to do too much at one time and then crashing can worsen fatigue.

(19:00): Many complications after a stem cell transplant or CAR T-cell therapy directly cause fatigue such as low blood cell counts, inflammation, dehydration, inadequate nutrition, graft-versus-host disease (GVHD),  changes in lung and thyroid function, and sleep apnea.

(21:47): Prescription medications such as is bupropion and stimulant medications help relieve fatigue in some patients.

(23:40): Polypharmacy – being on a lot of different medications – such as those that treat nausea, pain, sleep disorders, anxiety, allergies muscle problems and blood pressure – can contribute to fatigue.

(25:33): Going to bed and waking up at the same time each day helps combat fatigue.

(28:38): Cognitive behavior (CBT-I) is the gold standard for treating insomnia that contributes to fatigue.

(31:54): Using bright light therapy may improve your circadian rhythm or sleep/wake cycle.

(33:11): Emotions and stress affect one’s energy level. Incorporating regular movement into your day, prioritizing sleep, and using techniques like mindfulness to manage stress can positively affect your energy level.

Transcript of Presentation

(00:00): [Marla O’Keefe]:  Introduction. Good morning. My name is Marla O’Keefe and I will be your moderator for this workshop. It is my pleasure to introduce today's speaker, Dr. Erin Costanzo. Dr. Costanzo is a clinical health psychologist and professor of psychiatry and psychology at the University of Wisconsin School of Medicine and Public Health.

(00:20): She also serves as the primary clinical psychologist for the University of Wisconsin's Stem Cell Transplant program. Her research focuses on the contribution of psychological factors to the health and well-being of cancer patients and the mind-body mechanisms that underlie these relationships with a special focus on blood cancer patients receiving transplant and cellular therapies. Please join me in welcoming Dr. Costanzo.

(00:51): [Dr. Erin Costanzo]: Overview of Lecture. Well, thank you so much, Marla, for that nice introduction. I'm going to be speaking today about Living Well after Treatment: Coping with Fatigue. I'm going to start by talking about strategies for being able to do the things that are most important to you when you have fatigue — some level of fatigue is pretty much par for the course after CAR-T cell therapy (chimeric antigen receptor therapy) or stem cell transplant — and figuring out how to manage when you're very fatigued.

(01:32): And then, in the second part of the presentation, we will talk about some of the ingredients of fatigue — things that make fatigue worse, that prolong fatigue and what you might be able to do to change some of those factors to improve fatigue.

(02:01): Fatigue is normal and expected after transplant and CAR T-cell therapy. The first thing that I want to say is that fatigue is normal and expected after transplant or CAR-T. These are some data from my research group where we tracked patients who had autologous or allogeneic stem cell transplant, covering the first six months after transplant. The main thing that I want to draw your attention to is that in the pie charts, the red part is our patients who have what we would consider clinically significant fatigue — fatigue that is high and interfering with day-to-day activities.

(02:49): What those pie charts show is that about two-thirds of patients are still experiencing clinically significant fatigue by six months after transplant, and pretty much everybody is experiencing clinically significant fatigue at one month after transplant. The graph shows what happens with fatigue. It goes up from pre-transplant to post-transplant, and then it recovers over time. But many people are still fatigued.

(03:20): There's also a lot of individual variation. Some people have much more severe fatigue, some people less and we don't always know how to predict who is going to have more trouble with fatigue.

(03:35): Fatigue can be a lingering problem for many years post-transplant. For those of you who are further along, we still see that fatigue can be a problem for patients for many years. According to data from our research group from the University of Wisconsin, about two-thirds of patients continue to have clinically significant fatigue. That dashed line on the graph shows that cut point for clinically significant fatigue. People are approaching more of a normal level of fatigue, but many people are not there. Again, this is really normal.

(04:13): Energy management strategies to address fatigue. So, when you are fatigued, what can you do about that? We're going to talk about three different strategies: prioritizing, pacing and gradually increasing activity.

(04:31): Prioritize activities that are most important to you. Prioritizing is just what it sounds like — picking and choosing the things that are most important to you to focus on. Sometimes I like to use a metaphor. A common metaphor for energy is your tank of gas. So, before your diagnosis, you probably had a full tank of gas to get through each day. You were able to do many activities in a single day.

(05:02): After cancer treatment — after HCT (hematopoietic cell transplantation) or CAR-T — most people are going to have less gas in their tank and not have the fuel available to do all the activities that you normally would. So, it can be helpful to think, I've got limited fuel. Where do I want to spend that? What's most important? And to adjust your expectations. You can't expect to be able to use a full tank of gas, so adjust to what is reasonable for you. That I find in my practice is one of the hardest things for people to do.

(05:44): Use and time your energy wisely. When I work with patients, one thing we try to do is to really think through: what are the things that are most important to me? Those don't necessarily have to be chores or should-do things, but also the things that give you joy and meaning and purpose. That could be playing a game with your child or grandchild. That could be sitting and having dinner with your partner. So, thinking about for you what are the most important things and then you want to keep that at a reasonable level, often choosing just two or three high priority things to do.

(06:27): Then when your fuel increases, you can always add more. But a lot of days we don't always think about it;  we often have in our minds 10, 20, 30 things that we want to do and that's just not reasonable or realistic for most people after treatment.

(06:47): Schedule important activities for the times of day when you have the most energy. The other thing to think about is that there's a lot of difference in when people tend to have the most energy. I am a morning person. I have the most energy and get the most done in the morning. My spouse is a night owl and he is very productive after dinner. You can think for yourself — or even observe after transplant — what time of day your energy seems to be the best. That's a good time for doing your highest priority or most energy-consuming activities. It’s probably not helpful to push yourself to do things after lunch when you're drowsy, for example.

(07:36): All right. One of the hard things that I just said is, essentially, you have an ‘energy budget’ now. Your budget is much smaller and adjusting your expectations to doing less. So that means there's going to be stuff on your list that is just not reasonable for you to do. Some things to think about are: what can I delegate? What can I ask somebody else to do? And: what can I triage?  What can wait until later? Or: can I just skip it altogether? Are there ways I can take a shortcut or do something an easier way? If you're wiped out, maybe you eat off paper plates that day so you don't have to do the dishes, for example.

(08:21): One thing when I'm working with patients, it's helpful for us to notice: what are the rules I have in my head about how things need to be done or how often they need to be done? It's often worth taking a good hard look at those rules and whether we can be flexible and do less, essentially.

(08:50): Resting too much and lack of activity can make fatigue worse. The next strategy on the list is called pacing. In introducing pacing, I'm going to talk about a couple of common cycles that we see with fatigue. One is what we call the underactivity cycle. This is very common. When you're tired, of course you want to rest. This makes a lot of sense and is a really obvious thing to do. Sometimes people rest too much and that extended resting decreases your fitness, so it takes less and less activity to make you feel tired. Then, also doing nothing can lead to feeling bored or depressed because you're not doing those things that are important to you. And when you feel depressed, fatigue gets worse. We can sometimes see a cycle where fatigue can get worse with over-resting or underactivity.

(09:51): Pacing yourself is important. Trying to do too much at one time and then crashing can worsen fatigue. Another very common cycle is what we call our boom-bust cycle. It might be that you're feeling like a little bit of energy one day or you're starting to feel a little bit better and then you do too much — you've probably had this experience — and then you crash. Or you might be the type of person who's used to pushing through having a lot of demands on your schedule and you try that same strategy. But instead of being able to push through, now you have a crash.

(10:25): What happens when you're overextending and crashing in that way is that your fatigue gets worse over time. This is sort of counterintuitive because people think, I just need to push myself. I need to do more, but reminding ourselves of this message can actually make things worse and prolong recovery.

(10:50): What we want to shoot for is what we call pacing. Really, this just means doing a little bit and resting a little bit and doing a little bit and resting a little bit. It means when you're doing an activity, taking breaks based on time and what you can do versus finishing the task.

(11:15): So, for example, it may be that normally I fold up all the laundry and put it all away. When I'm pacing, what I might do is I might fold laundry for five or 10 minutes, and then I go take a break, sit, put my feet up, get something to drink, do some stretching and then go back and do another bit of laundry. So, I'm breaking it up with rest or recharging breaks.

(11:48): It's often very tricky to figure out: how much time do I do something for? When do I take a break? How do I take a break? There's a lot of experimenting in getting it right, but just keep in mind to build in breaks and focus on taking breaks versus needing to do something from start to finish.

(12:15): It's very easy to lose track of time. Most of us are not good at being aware of time passing. When people are really working on pacing, what we recommend you do is to go ahead and set an alarm on your watch, on your phone or on a clock in your home and pick a time that feels reasonable for you to sustain. I would probably subtract a little bit out of what you think you can do, because we tend to overestimate. You might set your timer for 10 minutes and then take a break, and then set it for another 10 minutes and take a break. This is actually going to help you build up your stamina and be able to do more during the day.

(13:04): For the break, it doesn't mean that you have to lie down. You certainly can. But the most important thing is changing up your body position. So, if you're sitting, you might want to stretch a little bit or even go for a brief walk. If you're doing something more active, then you might sit and put your feet up — but doing something that feels recharging to you.

(13:31): You really want to make decisions based on how much time you're at an activity versus waiting until you start to feel fatigued, because often that crash can come very quickly. There's not an exact science to it and it's hard, because it will change throughout your recovery and even day-to-day.

(13:57): Although it may be counterintuitive, moderate physical activity is one of the best treatments for fatigue. The next strategy — and this is actually more of a strategy for improving fatigue — is gradually increasing your activity. When we look at the science, paced, moderate physical activity is one of the best treatments for fatigue. But the trick is, you have to be very smart about it to avoid that boom-bust and that overextending.

(14:24): Increase physical activity gradually. What we recommend is that you are very gradual about increasing your activity level and very intentional about it. This doesn't mean that I'm going to start going to the gym and do a workout for 45 minutes. This means things like adding in a walk around the block or even a walk down to the end of the driveway and back to get the mail. That might mean when you're talking to someone that could be a cue to stand up and walk around. Now everybody has a smartwatch that tells us when to get up, so you could certainly use that feature, too, or other things that might be part of your day where you can just stand up and get a little bit more movement in.

(15:12): The idea here, too, is to change up your body position. If you are sitting or lying down a lot, you want to be standing or getting up because that's going to increase your fitness and hopefully decrease your fatigue.

(15:30): Using a smartwatch or an inexpensive step-count pedometer is an easy way to track your activity. It can also be really helpful to track your activity in some way. You do not need to have a smartwatch or a fancy activity tracker to do this. You can buy a very simple step-count pedometer — at Walgreens, Walmart, Target, CVS — that is inexpensive. And just start tracking your steps.

(15:56): What we suggest doing there is putting on the pedometer when you get up in the morning and taking it off before you go to bed at night, and then just writing down what your steps are. Do that for a couple of weeks to get a sense of what your baseline is. Then what you want to be thinking about is increasing very gradually. We recommend about 10% every one to two weeks.

(16:23): This gives some guidance. If you were doing less than 5,000 steps at a baseline, which many people are — let's say your baseline is 3,000 — that means that after a week or two you're going increase your goal to about 3,200 steps. And then after another week or two, 3,400. And adjust very gradually.

(16:51): This is also helpful not just for people who find it more challenging to increase activity, but also for people who tend to get in that boom-bust cycle. So, if you are overdoing it, this gives you a way to see that visually as well. Let's say, again, that your baseline is 3,000 steps, and it's 1:00 in the afternoon and you've already done 4,000 steps. That means that you probably need to back off that day. This is a great way to gauge what you're doing.

(17:35): Fatigue is usually caused by a combination of factors. Okay. Now we'll move on to the second part of the talk where we'll talk about some of the ‘fatigue ingredients,’ if you will, and strategies to help with those. I am not going to unpack this really complicated diagram, but I put this up here to show that scientists and psychologists are trying to figure out all of the different mechanisms for fatigue after cancer treatment. We already know about many, many biological and behavioral things that contribute to fatigue. For nearly everyone, it's not just one thing, it's a whole bunch of things. That's why fatigue is so tricky to treat and to figure out. I'm going to be talking about what’s written in some of these circles in plainer language now.

(18:39):  We're going to start by talking about inflammation, which you may have heard of with your treatment. This is the body's immune response. Then, we're also going to talk about the CNS — or the central nervous system — and the role of the CNS in fatigue.

(19:00): Many complications after a stem cell transplant or CAR T-cell therapy directly cause fatigue. Before I unpack that too much, it is very worth noting that there are many complications of stem cell transplant and CAR-T that directly lead to fatigue. A big one is not having enough blood cells — having low counts. Other complications after treatment that can lead to fatigue include being dehydrated, not being able to get in enough nutrition and having complications of transplant like graft versus host disease (GVHD). And then there could be lung problems that make it difficult to get enough oxygen into your body, changes in your thyroid function and sleep apnea. You may have been diagnosed with sleep apnea already. It can get worse with treatment or you may not have a diagnosis and that can become a problem after treatment.

(19:55): So, what do you do about this? The most important thing is to keep your doctor up to date on where your energy level is, and especially if you notice if it's changed a lot or gotten worse. Then, you can ask, "What tests or evaluations might be done for my fatigue?"

(20:20): Inflammation is the body's immune response. Sometimes the body can overrespond, and that happens with CAR-T, with cytokine release syndrome or ICANS (immune effector cell-associated neurotoxicity syndrome), which you've likely heard of if you're a patient who has been through CAR-T. In transplant, graft versus host disease (GVHD) involves inflammation. Getting an infection after treatment induces inflammation. Both radiation and chemotherapy trigger inflammation. Those are things that cause tissue damage, and the body responds with inflammation.

(21:00): Inflammation in the body talks to the brain. So, when we have inflammation in our body, messages get sent to the brain and the brain does what I might call ‘energy conservation mode.’ It tells us we are tired; we need to slow down. That can be really helpful and adaptive if you have an acute flu or infection, but it's not so helpful when you have that going on all the time, and then you're likely to feel fatigued. This is one of the biological reasons that people feel fatigued. Again, talking to your doctor is the most important step there.

(21:47): Prescription medications can help with fatigue. Other things that you can ask about or look into are medications that can be used to help with fatigue. Those might be medications for treating a complication that is leading to fatigue, and that's where your doctor comes in. There are also some medications that have evidence for improving cancer-related fatigue. One is bupropion which is a type of antidepressant. It's not one of the typical antidepressants we start people on, but it is an antidepressant that tends to be energizing in addition to having mood effects. It also helps with fatigue after treatment.

(22:40): Another classification of medications are stimulant medications. These are medications that are typically used to treat some types of sleep disorders, as well as attention deficit disorders, and can also be used for fatigue. We tend to use these medications when the fatigue is really getting in the way for people and isn't improving. Those are things you can talk with your doctor about.

(23:12): Poor nutrition can affect fatigue. Paying attention to nutrition is important. You may have access to a dietician or nutritionist through your cancer center who you can talk with, and talk about what your diet looks like and what you might do to improve your energy. Getting enough calories and protein are things to think about. The American Cancer Society has a nice set of guidelines about nutrition after treatment that I think is worth a look.

(23:40): Okay. Another factor with fatigue is something we call polypharmacy — which just means you're on a lot of different meds. Most people are on a lot of different meds after treatment. The problem is a lot of meds do the thing that they're supposed to do, and they might affect the brain and central nervous system in a way that kind of turns down the nervous system and causes fatigue. Common medications that people are on after treatment are anti-nausea medications, pain medications, sleep medications, anxiety medications, allergy meds, muscle relaxants and blood pressure medications. Many of these kinds of medications have fatigue as a side effect.

(24:35): The polypharmacy — what that means is, it's not always ‘one plus one equals two.’ Sometimes it's ‘one plus one equals four.’ So, if you're on two or three medications, that can cause fatigue. Sometimes that can really lead to severe fatigue.

(24:50): The other thing is alcohol. Avoiding or minimizing alcohol use — which can often interact with the medications in and of itself — is recommended because alcohol can depress your nervous system in a way that leads to fatigue.

(25:07): So, what to do about this? You can ask your pharmacist or doctor to review your medications, let you know which ones might have fatigue as a side effect and to think through a possible change. Sometimes there is a way. Some of these medications are necessary, but sometimes there can be a way to consolidate or shift medications to those that are less likely to cause fatigue.

(25:33): Keeping a consistent sleep-wake cycle helps combat fatigue. The next thing I'm going to talk about is the sleep-wake cycle. It probably comes as no surprise that when you're not sleeping well, you're going to be more tired during the day. So, when I see patients in my practice, looking at sleep is one thing that we often do to make sure that people are getting a good quality nighttime sleep. Most of these things you've probably heard before — avoiding screens before bedtime and giving yourself time to wind down and let go of the day.

(26:11): Two things I want to emphasize, though, are keeping a really consistent sleep-wake schedule. The best way to set your sleep schedule is to get up around the same time each day.

(26:29): The other piece is we want to set up a really good association with being in bed and being sleepy or asleep. What that means is, if you're in bed and you've woken up at night — or you've tried to go to bed and you really weren't sleepy and you're doing a lot of mental activity, planning, or problem-solving, or thinking about your worries — it's best to get out of bed for a little bit and then return to bed when you feel sleepy. That's often the last thing we want to do, but it can be really effective with setting up a good association with being in bed and being sleepy or asleep.

(27:07): A lot of people wonder about naps because many people need naps after CAR-T or stem cell transplant. Sometimes when you read about sleep strategies, they say don't take naps, but you may need a nap. What I talk about with patients is what I might call ‘smart napping.’ You want to take your nap around the same time each day. You want to shoot for a late morning or midday nap, which is hard. We all like that idea of that late afternoon nap or that after-dinner nap, but that is going to be much more likely to interfere with your nighttime sleep in an unhelpful way. So, try to get those naps done midday.

(27:49): Then, you want to get up after about 60 minutes. You could set an alarm or have somebody in your house wake you up. The reason being, if you're sleeping a lot longer than that, then you go into some deeper phases of sleep that can interfere with your sleep architecture at night. So those are things to think about with naps.

(28:15): If you're having trouble sleeping, talk to your doctor. You may benefit from a sleep study. These can often be done at home because it's not unusual to be diagnosed with a sleep disorder after this treatment. Or if you've had a sleep disorder already, sometimes that can change or get worse.

(28:38): If you don't have a sleep disorder or it's well managed and you're still having difficulty sleeping, the gold standard treatment is cognitive behavior therapy for insomnia — or CBTI. You can ask about that treatment. There are psychologists and other professionals who do that treatment. Sometimes it can be hard to access a professional who's trained in CBTI. And if that's the case, or if you want to give it a go on your own, the strategies are not super complicated.

(29:14): End the Insomnia Struggle: A Step-by-Step Guide to Help You Get to Sleep and Stay Asleep by Colleen Ehrnstrom PhD ABPP and Alisha L. Brosse PhD is a book that I recommend. I think it's excellent, very straightforward and helps you come up with a plan to help with your sleep. If you're an app person, the VA has an excellent app called CBT-I Coach that is free and available to anyone. You don't have to be part of the VA to access it.

(29:38): Getting your circadian rhythm back on track can help you manage fatigue. That brings us to another concept, which is circadian rhythms. Your circadian rhythm regulates the timing of when you are awake and when you are asleep, when you're active and when you're resting. You can think about it as your body's clock. What happens with many people after CAR-T and transplant is your body's clock gets super messed up and out of whack. This happens from being in the hospital, from having your whole daily routine disrupted, from not being able to be as active as you were before, from medication and treatment as we've talked about and from feeling stressed or overwhelmed. Those are all things that can affect your circadian rhythm.

(30:29): There's also some interesting new research showing that our patients don't get as much sunlight after treatment. Not surprising if you're spending a lot of your time in a medical clinic or a hospital or indoors. And that may be another thing that affects circadian rhythms for cancer patients.

(30:52): I'm not going to belabor this, but these are also some data from our lab. We set people up with a fancy kind of activity tracker and look at movement. The first one shows a pretty normal rhythm with less movement at night — which is at the beginning — and then a lot of movement during the day. After transplant, you can see what happens to the rhythm. It gets less, and it's all 24 hours people are up and down but not moving as much. We've got a lot of good data that the rhythm gets disrupted, and you've probably experienced that if you've been through transplant or CAR-T.

(31:32): What we want to do is think about increasing daytime activity — which we already talked about with activity management and using an activity tracker — and then improving your nighttime sleep quality, which we have just been talking about, and setting up a regular sleep cycle.

(31:54): Using bright light therapy may improve your circadian rhythm or sleep/wake cycle. Another more direct intervention for disrupted circadian rhythms is bright light therapy. There's some interesting research coming out looking at using bright light therapy after stem cell transplant. There's no data that I know of for CAR-T, but I think it also applies. And if you want to try this, you can purchase a light box. They're available in a number of places. You can sometimes get a prescription for one from your provider, but also check Amazon.

(32:31): What to look for is a therapeutic light box that is at least 10,000 lux, which is a light measurement. The larger the box, the more effective. The way to use it is to turn it on for about 20 to 30 minutes close to your wake-up time. What that does is it talks directly to your brain — the part of your brain that sets your rhythm — and it tells your brain it's morning. What we see with light box use, at least in the data coming out, is that patients report less fatigue, as well as more regular sleep and better mood.

(33:11): Emotions and stress affect one’s energy level. All right. And last, but not least, we're going to talk about the last circle, which is the neuroendocrine system and psychological stress. The neuroendocrine system is responsible for our body's emotions and stress response, to put it simplistically. We know that stress and mood can affect your energy level quite a bit.

(33:38): Daily movement, prioritizing sleep, practicing mindfulness and seeking connection and support with others can help reduce fatigue. The good news is there are a lot of things you can do to work on stress and mood. I know that that's been covered already in this conference series. You've hopefully gotten some good strategies from others. But the things at the top of my list as a psychologist that I think are really important to consider include, first off, regular movement. I don't mean going to a boot camp workout at the gym. I mean really paced movement, things that you enjoy.

(34:13): Prioritizing sleep is another one — which we already talked about. Seeking connection and support — the people in our life and our connections with them are some of the most helpful things for mood and stress. Mindfulness and mind-body practices — which I know have been covered in this conference — are great strategies to use.  And making space for difficult emotions. Sometimes when things are painful we want to push them away. But what is most helpful is to give them a little bit of room to breathe to pay them their due because having difficult emotions is normal in going through this type of treatment. And as we talked about before, doing activities that give you a sense of meaning and purpose.

(35:01): I have a recommendation here. The Healthy Minds Program app developed at the University of Wisconsin is a great tool. It's free. It's science based. It's excellent. I encourage you to check it out if you're at all interested.

(35:23): There are times that the self-management strategies may just not be cutting it and you may want to consult a professional. It's often most helpful to start with your hematology-oncology team or your primary care doctor for recommendations. But most health systems have psychologists, social workers, counselors, therapists and psychiatrists who help guide patients through regulating emotions and improving mood. Some of the indications that seeking professional support may be helpful are if you're feeling overwhelmed or unable to cope with anxiety or mood changes, your self-management strategies aren't working, or if the anxiety or mood changes are getting in the way of things that are important to you.

(36:15): Another thing that can often occur is that treatment situations may provoke anxiety that's difficult to manage. Most people feel a little bit uneasy when they drive past their hospital or come into the clinic. That's normal. But if that anxiety is getting in the way of being able to have your blood drawn or get a scan or see your doctor, that's something that we can treat very effectively.

(36:49): All right. I'm going to wrap up there. And I would love to take questions.

Question and Answer Session

(36:59): [Marla O’Keefe]:   Thank you, Dr. Costanzo, for this very excellent presentation. So, let's get started. Do people get fatigue after CAR-T and does it still occur one to two years after the therapy?

(37:32): [Dr. Erin Costanzo]:  Very good question. We don't have as good of data for CAR-T because it is newer. But yes, we are seeing fatigue and we are seeing that it can persist well after treatment. We just don't have really good numbers on that.

(37:57): But I think — for both transplant and CAR-T — developing sort of a persistent fatigue is not uncommon. Just because it is common doesn't mean you shouldn’t address it. So, thinking about some of the things that we talked about today, but also consulting with your doctor and letting them know, is important. Fatigue really is something that can impair your ability to do the stuff that's important to you, so we want to get to the bottom of that if we can.

(38:36): [Marla O’Keefe]:  The next question is, those of us with skin GVHD are told to avoid sunlight. Is it okay to use that sun box that you mentioned in your previous slide?

(38:50): [Dr. Erin Costanzo]: Great question. The light box is safe to use with skin GVHD. If you have any eye GVHD, chat with your doctor first. It's not necessarily a problem, but it is worth double-checking that that's going to be okay. But for skin GVHD, it should not be a problem. The light box filters out the harmful UV lights, so it's really just a way for your brain to get the message that the sun has risen without actually being in the sun.

(39:38): [Marla O’Keefe]: Thank you. My spouse is five months post-transplant and naps a lot during the day. Should I wake him up and get him to talk or should I let him sleep when he wants?

(39:52): [Dr. Erin Costanzo]: I would say, again, think about the smart napping strategy. Absolutely, he may need a nap during the day. But I would try to have him take it around the same time each day, kind of late morning to midday. And if he's napping for more than an hour or so, it would be a good idea to wake him up. You don't have to necessarily make him talk but have him get up and do whatever it is that you'd like to do.

(40:25): [Marla O’Keefe]: You mentioned this a little bit in your presentation, but what are the medications that are safe to take for fatigue?

(40:35): [Dr. Erin Costanzo]: Great question. One of the medications that I mentioned that is most commonly prescribed and that we have some evidence base for is bupropion. The trade name for that is Wellbutrin®. It is typically safe and effective, but it is a good idea if you're having someone other than your hematologist or oncologist prescribe that for you, to double-check with your cancer doctor to make sure it doesn't interact with any of your treatments. It doesn't typically for hematologic cancer patients, but it’s worth checking.

(41:12): Then, the other one includes stimulant medications which are generally safe and well tolerated, but they sometimes can't be used when people have difficulty with hypertension or cardiovascular concerns. So, this is a good conversation to have with your doctor to make sure that you don't have risk factors that would prevent using these medications, and to pick an alternative if those aren't available for you.

(41:47): [Marla O’Keefe]: Thank you. Are there any studies for patients affected by fatigue after six years —  for example, 10 to 15 years out? I'm interested to learn if fatigue improves.

(42:03): [Dr. Erin Costanzo]: Yeah, my graphs may have felt a little bit depressing because on average we saw that fatigue kind of persisted for a lot of people. What the graphs don't show is there's a whole lot of individual variation. And for many people, we see a gradual, gradual improvement over time, but we do have a subset of people who sort of get to a point and they don't really see their energy improve a whole lot. And we don't have a great way to predict which camp people might fall into.

(42:41): There are data to show that a proportion of long-term survivors still do have what we would think of as clinically significant fatigue even decades out from transplant. We don't have that data for CAR-T yet that I'm aware of. I think the take-home is it's not unusual, it can be normal and there are things we can do about it. It's complicated. There are a lot of factors, though, that we can think about to see if we can improve your functioning.

(43:26): [Marla O’Keefe]: Thank you. Is a morning cup of coffee helpful or harmful in the overall fatigue cycle?

(43:37): [Dr. Erin Costanzo]: For most people it's absolutely fine. Having kind of a morning wake-up routine can be helpful. A little bit of caffeine is going to give you a little bit of an energy boost. But if you're fatigued, sometimes the tendency can be to have a second cup and a third cup and have another cup in the afternoon. So, what you really want to watch is not having caffeine after early afternoon because that can interfere with your nighttime sleep and make fatigue worse. But, by all means, please indulge in your cup of coffee in the morning.

(44:20): [Marla O’Keefe]: Thank you. The recommendation of ‘no screens before bed’ — does that include TV? My wife and I like watching music videos. Is there a difference between TV and computers and that light and the impact on your sleep?

(44:38): [Dr. Erin Costanzo]: It's a problem with both TV and computers. The bigger the screen, probably the more of a problem. Some computers, tablets and phones have a night shift that you can turn on. That helps a little bit.

(44:55): But I would say a couple things. If you're not having trouble falling asleep and that is relaxing and part of your wind-down routine, then I would not worry about it. If you are having trouble falling asleep or your sleep is disrupted, then that might be something to think about changing.

(45:15): You mentioned music. You could listen to music. That would absolutely be something you could do. Listening to an audiobook or reading or something else may be a better way right before bed. But again, if your sleep's not disrupted, then I would keep up with your routine.

(45:37): [Marla O’Keefe]: Thank you. Are there any particular foods that are good for increasing my iron — I'm a little low on iron and I'm a diabetic — that will also provide me good energy?

(45:55): [Dr. Erin Costanzo]: I am going to defer on that question. I don't have a lot of expertise in nutrition. Probably what I would tell you is stuff that you already know. But you may want to check if there is a nutritionist or a dietitian available through your cancer center or your health system. Often, they can do a consult and look at your blood work. Also, if you are a diabetic, you may have access to that through your diabetes clinic and give you some guidance on that. But it's a great question and a good thing to be thinking about.

(46:39): [Marla O’Keefe]: Thank you. What are your thoughts on ®Ambien-type medications when you've tried CBT, sleep studies and are seeing a sleep hygiene specialist and nothing else seems to work?

(46:55): [Dr. Erin Costanzo]: Great question. I realized I skipped that bullet point on my slide. Often, people do benefit from sleep medication, and there are a variety of kinds of sleep medication. ® — or zolpidem — is one type of sleep medication that is commonly prescribed.

(47:16): My general recommendation on that is those can be very helpful and effective, especially when your sleep is really disrupted during early recovery or if it's disrupted for some other reason. The idea is using that medication to help alongside the other strategies — the CBT-I strategies and the things you're working on with your sleep specialist. Then, hopefully as the strategies take hold, you may be able to taper off that medication or reduce the dose.

(48:00): We generally don't like to have people on sleep medications long-term just because they tend to not work well over time, or they aren't as effective. So, if you're on a sleep medication and you're feeling like, "I'm still needing this," it may be worth adding some other tools to your kit. But it sounds like, from the person asking the question, they're already doing that. So, yes, I think that makes sense.

(48:30): [Marla O’Keefe]: Thank you. I think this is probably back in your slides, but two people wanted to know the name of the book you reference for CBTI and also the name of the app you mentioned.

(48:47): [Dr. Erin Costanzo]: Let me see if I can find that in my slides and I will put that up so everybody can see it. Okay, the book is called End the Insomnia Struggle: A Step-by-Step Guide to Help You Go to Sleep and Stay Asleep. The app is called CBT-I Coach. If you Google that or you put it in your phone's app store, you should be able to find it. But it is available through the Department of Veterans Affairs (the VA), if you're having trouble. So, you can also check out their website. Then, feel free to download the slides, and then you've got this information as well.

(49:37): [Marla O’Keefe]: Yes, thank you for that. The slides are downloadable so everyone can see them. A couple of people want to know, is it possible to ever get the same level of energy back after your transplant?

(49:55): [Dr. Erin Costanzo]: Yes, it is possible. We do see in our data set that there are people who do return to sort of their baseline. There are even some people who have more energy perhaps because their blood condition was causing fatigue for a while before the diagnosis. So, there's just really a lot of individual variation. But I think one thing to think about is that as we get older, we have less energy. For most people, our energy isn't increasing over time, especially those of us who are in our middle-age years or older. It's normal to have less energy over time.

(50:47): A phenomenon that we call ‘accelerated aging’ can occur in people who have had a lot of cancer treatment, meaning biologically you are aging a bit faster than other people who haven't had so much happen to their body. So, on average, we're going to not see things returning to pretreatment levels necessarily. Then, of course, with all of the different possibilities for complications and other issues, it can be hard.

(51:26): That said, what I like to think about with people is making the goal of let's do what we can to improve your energy to the best that we can get it with some of the strategies that we talked about, or medications or addressing treatment complications. Then, based on where we can get you, let's help you live as well as possible with what you do have. And you can learn. You can work on and practice some of those energy management strategies so that you can do the things that are important. But you may not get back to the time when you could get 40 things done and be running throughout the day. So, a lot of it is kind of figuring out your new set of expectations for yourself.

(52:24): [Marla O’Keefe]: Thank you for that very thoughtful answer. This is another one. I feel that people may judge me for taking breaks if they aren't aware of my situation. What's a good way to deal with that or let people know?

(52:39): [Dr. Erin Costanzo]: Yeah, that's a great point. That is so hard because fatigue is not something other people can see. Often, people who know you are so happy you're done with treatment and tell you how good you look. Your own expectations — it's hard to line those up often with what your body can do. And it's really hard when the expectations from other people may not be realistic either.

(53:06): So, the best strategy is really just to be straight with people. "I am better. I'm doing well. And one of the long-term effects of my treatment is fatigue. I handle it by needing breaks." Or even just being straightforward and saying, "I'm going to need to take some breaks throughout this activity we're doing." I would be as upfront as possible. Most people want to be kind and accommodating. So, if you keep that in mind, most people are looking for your direction in how to be helpful.

(53:47): [Marla O’Keefe]: Thank you. This is going to be our last question. Melphalan from BMT (bone marrow transplant) causes fatigue. Is that because it's based in mustard gas?

(54:03): [Dr. Erin Costanzo]: I don't know the answer to that question. A lot of what melphalan and other chemotherapeutic agents are doing, as you may know, is killing cells that are fast dividing. And that includes both your cancer cells but also healthy cells and tissues. So often, it is the effects on those healthy cells and tissues and then your body's response to that — with trying to have your immune system kind of come to the rescue and healing and doing a lot of tissue repair and remodeling — that takes a lot of energy from your body and leaves you with less energy. That's my general answer to most kinds of chemotherapy and radiation therapy, but I don't know specifically about melphalan.

(55:03): [Marla O’Keefe]: Thank you. On behalf of BMT InfoNet and our partners, I'd like to thank Dr. Costanzo for a very helpful presentation. Thank you, the audience, for your excellent questions. Please contact BMT InfoNet if we can help you in any way.