Managing Fatigue after Transplant: Creating Strength through Recovery

Chronic fatigue is a common problem after a stem cell transplant and is often not helped by sleep alone. Learn what contributes to chronic fatigue after transplant and effective ways to manage it.

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Managing Fatigue after Transplant: Creating Strength through Recovery

Thursday, May 5, 2022

Presenter: Sandra Mitchell PhD, CRNP, FAAN, National Cancer Institute

Presentation is 35 minutes long with 24 minutes of Q & A.

Summary: Chronic fatigue is a very common problem after a stem cell transplant. It is usually caused by a combination of factors, rather than a single factor, and can persist for a long-time. This presentation discusses factors that contribute to chronic fatigue and effective strategies that can reduce the impact of chronic fatigue on daily life.


  • Thirty-five percent of transplant recipients who do not have graft-versus-host disease (GVHD) report severe fatigue after transplant; for those with GVHD, the incidence is 70-80%.
  • Talking with healthcare providers about fatigue is not “complaining;” they can often help if they know how and when you are experiencing fatigue.
  • Drinking at least 10 glasses of water or other non-caffeinated beverage and eating sufficient protein and carbohydrates each day can help reduce chronic fatigue.

Key Points:

(07:23): Chronic fatigue is usually not helped by getting more rest or sleep, alone.

(08:13): Fatigue can increase emotions like sadness and irritability, affect memory and make it more difficult to complete tasks.

(09:19): In order for healthcare professionals to help with fatigue, they need to know when it started, whether it has changed over time, what makes it better or worse, and if it is associated with other symptoms like pain or difficulty sleeping.

(13:53): Hypothyroidism is a common after transplant and can contribute to fatigue.

(15:13): Good quality sleep is important in managing fatigue, but it’s important to avoid too much sleep.

(16:18): Cognitive behavioral therapy for insomnia (CBT-I) is a more effective tool for improving sleep than many sleep medications.

(17:05): Physical activity that strengthens muscles and improves stamina is critically important to reduce fatigue.

(22:28): Energy conservation strategies like pacing yourself, scheduling your day so that important tasks are done at a time when you have the most energy, and delegating tasks to others can help reduce fatigue.

(29:23): Bright light therapy may improve daytime fatigue and nighttime sleep quality.

(32:59): Communicating with employers and co-workers about feeling fatigued and asking for help when needed is important. The Americans with Disabilities Act may enable you to ask for a modified work schedule or other accommodations if you are dealing with chronic fatigue.

Transcript of Presentation:

(00:01): [Marsha Seligman] Introduction. Hello everyone. Welcome to the workshop, Managing Fatigue After Transplant: Creating Strength through Recovery. I'd like to introduce to you our speaker, Dr. Sandra Mitchell.

(00:13): Dr. Sandra Mitchell is a senior scientist in the outcomes research branch of the National Cancer Institute, Division of Cancer Control and Population Sciences. A board-certified acute care nurse practitioner, Dr. Mitchell maintains a clinical practice in survivorship care and conducts research with the NCI Intramural Research Program, focusing on long-term survivors of stem cell transplantation, experiencing chronic graft-versus-host disease and other long-term and late treatment effects. Dr. Mitchell is the author or co-author on more than 150 articles and book chapters on quality of life issues in cancer patients and transplant recipients and has lectured extensively on quality-of-life and late effects after transplant. Please welcome Dr. Mitchell.

(01:06): [Dr. Sandra Mitchell] Overview of Talk. Thank you so much, Marsha, and I am so pleased to be here today to speak with the audience about evidence-based management of fatigue following stem cell transplantation. Our focus will be on creating strength through recovery. And I would like to acknowledge Sue Stewart and BMT InfoNet, for the opportunity to present to you here today. As Marsha mentioned, I have some remarks that I will make. And then I really look forward to receiving your questions and discussing some ideas and exchanging information with you.

(01:57): As Marsha said, I am a senior scientist here at the National Cancer Institute, and I practice in our Chronic Graft-versus-Host Disease Clinic and study group. The views expressed are not necessarily the views of the NIH or any other government agency. I have no conflicts of interest to disclose. So let's get started.

(02:19): Fatigue is one of the most common problems after transplant for both patients and caregivers. I think that as everyone probably here in this room knows, fatigue is one of the most common symptoms experienced by individuals coping with cancer treatment and recovery. And it's also experienced by caregivers and family members. If you have been experiencing fatigue, and I think almost all of us have experienced fatigue at one point or another in our lives, we know that it can be associated with physical, psychological, social and spiritual distress. Coming along with fatigue can be decreased physical activity, changes in mood, sleep disturbance, and changes in role function. It can also raise for us questions about quality of life.

(03:05): Thirty-five percent of transplant recipients who do not have graft-versus-host disease (GVHD) report severe fatigue after transplant; for those with GVHD, the incidence is 70-80%. When we think about fatigue in the context of transplant recovery, our research indicates that there's about a 35% incidence of severe fatigue long after transplant. That's excluding patients that have severe GVHD or anemia. When patients have severe GVHD, that incidence of fatigue can rise quite sharply to upwards of even 70 or 80%.

(03:34): Fatigue can be directly associated with the underlying disease for which people undergo a transplant, as well as with the therapy that they may have had for their transplant and for graft-versus-host disease.

(03:48): Fatigue is a persistent, subjective sense of tiredness that interferes with usual functioning. So what is fatigue? Well, we define it as a persistent, subjective sense of tiredness that interferes with usual functioning. It often persists over time, and it can interfere with the performance of usual activities such as our roles as workers, as parents, as spouses, as friends. It may also be more severe and distressing than the fatigue of everyday life.

(04:17): And many of our patients tell us this, that they've had fatigue in the past, but this kind of fatigue is more severe, more distressing. And interestingly, rest doesn't always relieve that fatigue, and that can be quite difficult to cope with.

(04:36): Fatigue is usually caused by a combination of factors including anemia, depression, pain, insomnia, uncontrolled side effects, infection, malnutrition, dehydration, deconditioning, and medications. So when we think about contributors to fatigue after transplant, the causes of post-transplant fatigue are multifactorial. They can include things like anemia or low hemoglobin, uncontrolled symptoms, depression, pain and insomnia. Infection can contribute to fatigue. Malnutrition and especially dehydration can make us feel more fatigued. Cardiopulmonary deconditioning and immune dysfunction also both contribute to fatigue. And sometimes fatigue is caused by medications that we take that have side effects that act on the brain. So in any individual person, fatigue almost always has several different causes. And as such, the treatment plan really needs to be individualized and we'll say more about that in a minute.

(05:33): Fatigue is not inevitable and can be effectively treated. So I want to just address some misconceptions because many times individuals believe that fatigue is an inevitable side effect, and it is not an inevitable side effect. It can be quite common, but it is not inevitable. Sometimes too people say, 'well, I just don't want to be a complainer. I don't want to complain about fatigue. I'm really glad that my disease is in remission or I'm doing well or I'm able to get back to work. I don't want to be a complainer.' Related to that is sometimes people just say, 'well, this is just something I have to accept'. And the last misconception is that there are no effective treatments. So the take home message here is that this is not inevitable. It is not something that you just have to accept. And there are effective treatments.

(06:29): Talking with providers about fatigue is not “complaining;” they can often help if they know you are experiencing severe fatigue. With respect to a misconception that you're a complainer, you have to talk to your providers, your professionals. You have to talk to us about this symptom so that we know how much it's bothering you and in the ways in which it's bothering you, so we can begin to understand what might be contributing and then what we can do about it. So again, the facts; fatigue is common, but not inevitable. Fatigue can limit resumption of an exercise program and can interfere with family, social and vocational function. So you're not complaining. It truly is a problem to be addressed. And treatment of fatigue, just like other symptoms, is critical to your full recovery and quality of life. So it's not something you just have to accept, and we do have effective treatment strategies.

(07:23): Chronic fatigue is usually not helped by more rest or more sleep. And so what are some of the ways that fatigue may be experienced? And this is important to note because some of these are intuitive and some are not. So, obviously, fatigue, when we're fatigued, we feel like we have diminished energy, and we need to rest. But sometimes fatigue is manifested just by a generalized weakness or a sense of limb heaviness. We may experience fatigue as just not being motivated.

(07:50): We may experience fatigue as sleeping too much, but some patients with fatigue actually say that they can't get to sleep, that they have almost insomnia. They're so exhausted, but yet they can't get to sleep. Fatigue is sometimes also experienced by what we call sleep that is non-restorative, and that means you wake up tired.

(08:13): Fatigue can cause sadness and irritability. Other indicators of fatigue can include things like marked emotional reactivity. You may be sad. You may be frustrated. You may be irritable, and this is very common among my patients who will say, 'I can tell I'm getting fatigued, because I'm just... everything irritates me.'

(08:30): Fatigue can make it more difficult to complete tasks and affect memory. Fatigue may also manifest as difficulty completing daily tasks, problems with short term memory. And then, notably, this feeling of malaise, which is kind of like a feeling of weakness or just feeling badly, feeling unwell. And this can sometimes last for several hours after an exercise or exertion. So those are some of the ways in which fatigue is experienced.

(08:57): Emotionally, fatigue can be a frustrating reminder of what you've been through and what you're coping with now. It can make the future seem uncertain and the unpredictability of fatigue can make this a very difficult symptom to manage. And that's something that many of our patients do comment upon, is that this can be very unpredictable.

(09:19): In order for healthcare professionals to help with fatigue, they need to know when it started, how long it’s lasted, whether it has changed over time, what makes it better or worse, and if it is associated with other symptoms like pain or difficulty sleeping. So as professionals, when we hear that someone is fatigued, we want to start to ask some questions and you can think about these questions for yourself as you prepare to discuss your fatigue with your healthcare professional. Think about when did this start, how long has it lasted? Has it changed over time? How did it start? What makes it better? What do you notice makes it worse? Do you have any other symptoms that go along with the fatigue, like pain or difficulty sleeping or getting up during the night to go to the bathroom a lot?

(09:57): And what are the consequences for fatigue? What are the ways that it interferes with daily activities and how much? And I recall a recent story of a patient, and he really felt like he didn't want to be a complainer. He was back to work, and he was very glad to be back to work and beginning to resume his life. But as we talked to him, I found that he really was experiencing a lot of fatigue. And when I talked to him about how much it was interfering, he said, 'no, I won't let it interfere.' But then as we got a little bit deeper, come to find out that at work, during his lunch break, he needed to go out to his car and lay down in the car just to be able to take a slight nap and rest. So there was interference with daily activities, although he was managing to surmount that.

(10:48): So thinking about some of the mechanisms of fatigue, this is a very active area of research. And as I said at the beginning, we have multiple mechanisms that contribute to fatigue. And in any individual person, it's probably not just one factor, it's multiple factors. But we do want to try to understand what some of the contributors are, because that may point some of the ways that we want to begin to try to intervene and treat this.

(11:16): Chronic fatigue can be the rest of cellular waste products building up in the body, graft-versus-host disease, sleep disturbances, depression, stress, low blood counts, organ problems or loss of muscle mass. So mechanisms of fatigue include the buildup of cellular waste products. The release of cytokines, as a result of the inflammatory process, particularly with chronic graft-versus-host disease. Fatigue can develop because we have increased energy needs. Fatigue often develops in the setting of sleep disturbances and depression, as well as stress. It often develops when there's anemia, which is a low hemoglobin and or red blood cell count. Fatigue very much can develop when we lose muscle mass because we're not able to exercise or because we've been in bed a lot.

(11:56): Sometimes fatigue indicates that there is cardiopulmonary dysfunction, so a problem with the heart or problem with the lungs. Dysfunction of the thyroid and the adrenal gland also can cause fatigue as can infections, electrolyte disturbances, dehydration, unmanaged symptoms such as pain and medication side effects.

(12:22): So when you're talking with your healthcare team about your fatigue, it's important to highlight any symptoms that you think may be associated or going along with your fatigue or maybe making it worse. And I've listed some of these on the slides, depression, anxiety, sleep difficulties, getting up at night to urinate, having peripheral neuropathy, muscle cramping and reduced physical function, reduced strength, reduced endurance.

(12:50): When discussing fatigue with your doctor, provide a list of all prescription and over-the counter medications you take as well as any vitamins or supplements. We want to know all the medications that you're taking, both prescription, which we do tend to know about, but also any over the counter or nutritional supplements. Also, when you talk with the healthcare team, think about your nutrition, including your hydration. Most of us, I say, are wandering around dehydrated. I call that being short a quart of oil, but many of us are wandering around daily somewhat dehydrated. And then what are you doing about an exercise plan? How have you been able to move forward with that?

(13:25): So when we think about anemia, hypothyroidism and adrenal insufficiency, these are three laboratory abnormalities or organ system dysfunctions that we can test for in someone who is fatigued. Anemia is tested with a simple blood test. And if hemoglobin is extremely low, we may consider the benefits and risks of what are called erythropoiesis stimulating agents.

(13:53): Hypothyroidism is a common after transplant and can contribute to fatigue. With hypothyroidism, it's very important to note that this is common in post-transplant patients, especially those who have had certain kinds of cancer treatments like total body radiation and a medication called Sunitinib. We test this with a simple blood test and it's important that we be tested on an annual basis for hypothyroidism, which can increase as we age. It can increase particularly in women; its prevalence increases over time. And then as I said, many of our prior cancer treatments can put you at risk for hypothyroidism. So it's tested with a simple blood test and then we compensate with thyroid hormone.

(14:40): Prolonged steroid use can cause adrenal insufficiency and contribute to fatigue. Similarly, adrenal insufficiency can occur after prolonged treatment with steroids, and we are learning more about how even prolonged treatment with topical steroids, so that's steroids to the skin, to the vagina or to the mouth that there is some systemic absorption with this. And so if you've had prolonged treatment with steroids and you're feeling fatigued, we can test your adrenal insufficiency with a simple blood test. And again, we compensate that with replacement of low dose hydrocortisone.

(15:13): Good quality sleep is important in managing fatigue, but it’s important to avoid too much sleep. Also important are rest and sleep. Rest and good quality sleep are critical, but we don't want to overdo it. Too much resting can actually decrease your energy and very erratic sleep patterns can also create difficulty with sleeping properly at night. We won't go into a lot of detail about this today, we could do a whole talk on rest and sleep, but we encourage patients only to nap for an hour or less during the day so that you sleep well at night. And if you have to, set an alarm or have a family member get you up and almost force you to at least get up. You may be tempted to want to take long naps, but those tend to lead to sleep disruption at night and it becomes a vicious circle. So we also encourage people to go to bed and get up at the same time each day, regardless of the quality of sleep they had the night before. And again, you might want to sleep in, but those erratic sleep patterns become a very difficult circle to interrupt.

(16:18): Cognitive behavioral therapy for insomnia is a more effective for improving sleep than many sleep medications. There's a lot more information at the website listed here in your slides. It addresses what we call cognitive behavioral strategies. These have been proven, much more than medication, to improve sleep quality. And if you think you have a sleep disorder like restless leg syndrome or sleep apnea, if your sleep partner tells you that you're moving your legs a lot at night or that you are snoring a lot, it may be worthwhile to see a sleep medicine clinic and consider a sleep study. And more about these issues will also be available in the symposium workshop on sleep problems after a transplant, which is also taking place during this set of sessions, and during this conference.

(17:05): Physical activity that strengthens muscles and improves stamina is critically important to reduce fatigue. Really critically important is physical activity. There have been more than 70 systematic reviews of physical activity and exercise and its ability to improve fatigue. This is the most well-established intervention for fatigue, and every fatigued patient, even once they've been evaluated and even if we've found some other physiologic causes, everyone needs to be on a physical activity exercise plan. Physical activity and exercise strengthen our muscles. It makes us use our oxygen system much more efficiently. It enhances our stamina and endurance. It also has very beneficial psychological effects on depression, anxiety, and stress, and it markedly improves sleep. So it's 1-800-EXERCISE for all of us.

(18:00): Even small amounts of exercise can be beneficial. So how do you do this? Well, the first thing is just to try to stay active. Just stay on the move, do things at home, walk around the house, whatever it is that you can do. We do encourage people to exercise several times a day, just for short intervals. And we've shown that you don't have to exercise for 60-minutes. Five or 10 minutes, several times per day is equally beneficial to a 60 minute exercise and might actually be much more attainable without exhausting yourself so much that you induce that feeling of malaise that some very fatigued people will describe comes on when they do too much exercise. So we don't want you doing lots of exercise. Five to 10 minutes, several times a day. You can do stretching, light weights, walking, bicycling. Encourage people to set very short-term goals, just do five minutes, just 10 minutes as you're getting started.

(18:59): If you're just starting a walking program, just do two blocks and don't be tempted to say, 'I'm going to do four blocks. That felt so good. I'm going to do four blocks' No, stop yourself, and then increase your goals gradually. Sometimes exercising with a partner can be helpful and I really encourage people to find yoga, Tai Chi or Pilates classes that can enhance flexibility, balance, strength, and well-being. And although it's challenging, certainly during the pandemic and post pandemic to consider how to integrate some of these things with exercise classes and what-not, how to integrate those safely, each of you, based on your risk, status and immunosuppression and other considerations can talk with your team about that. But some Tai Chi and yoga programs are now being delivered in parks and other outdoor spaces.

(19:56): Physical therapists and exercise professionals can help develop an appropriate an exercise program tailored to an individual patient’s needs. So we're lucky with summer coming, for most of us, in nice weather looking at some of these outdoor exercise options can be great. And then very much, if you are interested to begin and advance an exercise program, and you're feeling very weak and very debilitated, referral to physical therapy or an exercise professional is very much something that I would encourage. And you don't have to go to physical therapy or an exercise professional every day or even every week. You can just spread those visits out a little bit and get some advice about what exercises to do and then how to advance your exercise program.

(20:41): Drinking at least 10 glasses of water or other non-caffeinated beverage is necessary to avoid dehydration which can contribute to fatigue. When you think about nutrition, I cannot emphasize enough the importance of drinking liquids. Dehydration alone can make you feel fatigued. And so we do encourage drinking at least 10 glasses of water or non-caffeine containing fluids at least every day. And it can be hard to drink water, but I do encourage water and avoiding sugary things and too much juice, that sort of thing.

(21:13): Definitely not something that I would encourage, but if you're having trouble getting water, because you don't like the taste or it just doesn't sit well with your stomach, you can consider things like broth. You can put a little splash of juice into your water. I'm somebody that, I don't like water, but I can drink more water when I put a little splash of juice just to give a tiny bit of flavor. So just a couple tablespoons of juice in your 10-ounce glass of water and that can make it a little bit easier to consume that.

(21:43): Consuming sufficient carbohydrates and proteins is important to help manage fatigue. Carbohydrates and proteins are very important and it's important that you consume sufficient calories. Some of the nutritional symptoms that patients experience such as appetite loss and mouth pain, difficulty swallowing, all of these can make it difficult to get the nutrition and fluid we need. So talk with your team about managing these symptoms.

(22:05): Supplements can be helpful if you're losing weight or muscle mass and you can't consume a usual diet rich in fruits, vegetables, and lean meats and fish. And again, I really encourage consultation with a dietitian if you're having nutritional issues and concerns or other kinds of appetite loss and some of those symptoms.

 (22:28): Energy conservation strategies like pacing yourself, scheduling your day so that important tasks are done at a time when you have the most energy, and delegating tasks to others can help reduce fatigue. One of the things that is recommended for very fatigued individuals is something we call energy conservation. And what this involves, just as the name says, is pursuing strategies that help you conserve and balance your energy across the day. And so some of these strategies are in the next few slides, things like sitting down to bathe or to prepare meals, organizing your time to avoid rushing, scheduling your day such that you have necessary activities at a time of day when you tend to have more energy and then pacing yourself throughout the day, which can be very challenging. A lot of my patients say to me, I'll have a day when I feel so good. I do a ton of stuff. And then the next day I feel horrible. And so pacing is very, very important. Breaking up the activity interspersing with rest, if needed.

(23:25): Delegating tasks to others is also important if you're coping with severe fatigue. Forgo activities that don't need to be done daily, such as in my house, making of the beds is one of the things that is foregone. But you have some other activities that you just say not important and I'm skipping that. When you're shopping, organizing the list by aisle can help you have to do less back-and-forth walking in the store. And shopping at less busy times leads to fewer lines and those kinds of things.

(23:58): Meal preparation strategies that conserve energy can help. Meal preparation can be challenging when you're very fatigued. Meal preparation takes lots of energy and effort. And so consider using convenience foods and food prep outlets are now a great option for homemade meals prepared with fresh ingredients. Keep healthy snacks and some small meals handy in your fridge, especially if you don't have the energy to prepare a meal. That can be something like a boiled egg, high protein cottage cheese, high protein yogurts. We're very lucky now that we have a number of dairy products that really have those very high protein components, and they can really help you with your nutrition. And then prepare double portions and then just freeze half so that you have those for another day.

(24:48): With childcare, try to plan activities for sitting down in the workplace. Alternate sedentary tasks with more demanding ones and planning your workload. And then again, just balance your activity and rest so that you don't get overtired.

(25:03): Attention-restoring activities like meditation and socializing with friends can be energizing. There are ways that we're exploring that are considered energy restoring and these can include activities that you enjoy and that make you feel good. But also cognitive fatigue there's been some small number of studies that have shown that, we call them attention restoring activities like bird watching, gardening, spending time in nature, listening to music, visiting with friends, looking at pleasant pictures, that all of these things can be actually energy restoring. And so I really encourage patients, instead of going and taking a nap, if you're feeling fatigued and especially that cognitive fatigue and sleepiness, consider one of these things to try to see if that will help produce some refreshment.

(25:52): Meditation, mindfulness-based stress reduction and relaxation and imagery also can help with energy restoration. And then remaining open to friendships and emotional support can also help with restoring energy. Sometimes with fatigue, those friendships and emotional support can go by the wayside.

(26:15): To improve mental concentration and attention, which is definitely a component of fatigue, we recommend getting together with friends, either in person or on Zoom, getting involved with group discussions. Very important to avoid spending all day at home alone, that can definitely be mentally fatiguing. Writing lists is critically important, and so that can help you stay organized and attending.

(26:46): Establishing regular routines for daily activities can conserve energy. Keeping yourself in a routine. For example, putting your keys into the same place, having your materials for leaving the house well organized. I have what I call my COVID bag that I just grab as soon as I'm walking out the door. And in there, I've got all my different types of masks that I need, my hand sanitizers, the wipes, all the different things that you're going to need. And I call that my COVID bag. I look forward to getting rid of the COVID bag by the way, but not quite yet.

(27:16): Ask a physician or nurse whether medications you take are interfering with attention or sleep. And then talk with your physician or nurse about medications that may be impairing your attention span, medications that may be interfering with sleep. And there are medications that we can prescribe that will help to improve attention and mental concentration. They do have side effects, but it's certainly worth talking with your team about the possible role that some of those medications that will improve attention might have for you.

(27:44): Reducing stress and mindfulness activities may improve fatigue. Other potential treatments that can be explored with your team are things like Wisconsin Ginseng if approved by your care team, practicing mindfulness-based stress reduction and progressive muscle relaxation and imagery. There's a pretty good body of evidence now coming forward about the importance of mindfulness-based stress reduction and its potential to improve fatigue.

(28:07): Antidepressants are not effective in reducing fatigue. The antidepressants have been tested, and if someone is experiencing depression, as well as fatigue, a trial of antidepressants can be helpful, but in general, antidepressants haven't shown a great effect just for fatigue alone. Although if depression goes along with that, they're definitely very much worth a try.

(28:30): Psychostimulants have not been shown to improve fatigue in studies but may be helpful for certain individuals. The psycho stimulants that I mentioned, things like methylphenidate are worth talking to your team about as are the wakefulness promoting agents modafinil and armodafinil. Again in trials, these have not shown generally strong results in improving fatigue, but they certainly, in selected individuals, can be helpful and can be worth a try, although they can cause some jitteriness and some problems with sleep. So it's important to work carefully with your team in trying these.

(29:03): Fish oil supplements may help with fatigue. Omega-three fatty acid supplementation, also called fish oil supplements, have been shown to favorably affect inflammatory processes, and probably by down regulating inflammation, Omega-three fatty acid supplements may be helpful for fatigue. So something to talk to your team about.

(29:23): Bright light therapy may improve daytime fatigue and nighttime sleep quality. Also promising is something called bright light therapy. And again, not a lot of studies and none that I'm aware of in post-transplant setting, but morning exposure to bright light seems to help with our circadian rhythm synchronization and can improve both daytime fatigue, but also improve sleep quality. So, that's morning exposure to bright light.

(29:51): And then massage, reflexology and acupuncture all are worth considering for fatigue. Acupuncture has also very large body of evidence. It's a complicated literature because it's hard to tease out what are the effects of just people's expectancy that the acupuncture's going to work. But there certainly is some, I would say, fairly good evidence that acupuncture is very much worth a try for fatigue.

(30:22): And then structured rehabilitation, that's related to getting physical therapy. Having a structured rehabilitation program can be very helpful for fatigue.

(30:32): Decreasing work and school obligations and setting realistic goals can help manage fatigue. So when we think about folks that are working or going to school and dealing with fatigue, I think it's important to realize that fatigue may interfere with the ability to work and here by work, I also include school and volunteer activities, those kinds of things. And so certainly fatigue can really interfere with the ability to function in those settings. Options include talking with employers and school personnel about decreasing hours, decreasing responsibility, taking a break from work or requesting a disability leave in order to address the underlying problems that are causing this very severe fatigue.

(31:29): It's really important to set realistic goals and to be compassionate with yourself. You've gone through a lot and the body has gone through a lot and there are ways to rehabilitate from this, but it is a rehabilitation process. And so it's important to set realistic goals and be compassionate. You can request, possibly, a change or modification in your job responsibilities, either permanent or temporary, that will allow you to better accommodate your fatigue and to use some of those pacing activities or pacing strategies that we talked about a little while ago.

(32:09): So what that might look like is that if you find you're more fatigued in the morning and you need a slower routine to ease into the day in the morning, that you are working at the office, on site from 12:00 to 6:00 or something like that. Modification or adjustment to job responsibilities, modification to the number of days you're coming into work, doing work from home, whatever makes sense for the various types of job responsibilities that people have and how their energy patterns are playing out for them. It can be really useful to talk with someone on your healthcare team about all of this and try to get some strategies and ideas from them about how you might think about this.

(32:59): Communicating with employers and co-workers about feeling fatigued and asking for help when needed is important. It's just really important to communicate openly with employer, with coworkers about the feeling of fatigue and not feeling embarrassed to ask for help. Again, we're all really anxious to get things back to normal when going back to work. And then also, understandably fearful that these kinds of requests could not be well received, I'll say more about that in a minute, but try not to be embarrassed to ask for that help. And then be sure that in returning to work, you're still eating regularly, drinking fluids and able to pursue a moderate exercise program.

(33:42): I had one patient that said to me, she said, 'I'm doing fine. I'm back to work, I'm coping fine'. But when I talked to her, pretty much every day, she came home from work, six o'clock and really had to just go to bed and lie down. And so while she was back working, the quality of her life outside of work was really restricted by that. And we were able to work on some strategies to improve her overall level of fatigue, and also to look at pacing.

(34:13): Laws like the Americans with Disabilities Act and the Family Medical Leave Act may enable you to ask for sick leave or other support from an employer. Very important to know the provisions of the Americans with Disabilities Act and the Family Medical Leave Act so that you understand your rights as an employee. And post-treatment fatigue is considered formally a diagnosis that we have in our international classification of disease. We call that the ICD code. So very important to know that you have rights, and you may have flexibility, like sick leave disability, flexible scheduling and work retraining. So familiarize yourself with your company policies. And again, count on your team to hopefully be able to write letters of support that might be needed to pursue things like sick leave and disability. And there's some good sources of information about employment rights and cancer that are listed on the slide. So I think with that I will turn this back to Marsha and to Sue to kick us off with some questions.


Question and Answer Session

(35:24): [Marsha Seligman]          Q & A. Thank you so much Dr. Mitchell for your wonderful presentation. We will now take questions. Our first question is, I had an allogeneic transplant for MDS in 2018, with a history of 67 blood transfusions over the years. My ferritin is very high, treated with phlebotomies. Will my fatigue get better after my iron levels are returned to normal?

(36:00): [Dr. Sandra Mitchell] That's a great question and you have brought up another potential cause of fatigue, which is that iron overload, as you've talked about. That can result when you've required a lot of blood transfusions. So the therapeutic phlebotomies are a way to treat that as the underlying cause. High levels of iron are, they have many effects. And this hasn't been super well studied, but they definitely have many effects. They cause inflammation. They can also cause some liver dysfunction and both of those can contribute to fatigue. So it's great that the one potential underlying cause is being treated.

(36:42): I think the two things are, with anyone who's fatigued, even when I have compelling evidence, for example, that they have adrenal insufficiency or thyroid dysfunction, I don't want to just assume that's the only thing going on. Nor do I even assume that it's the primary actor in that if I fix that, everything's going to be great. I tend to say, well, we've got a primary actor or a couple of primary actors here, but I want to be attending to all of those factors that I went through in the presentation. So in addition to therapeutic phlebotomy, I would really encourage the exercise program, attending to sleep, nutrition, fluid intake, stress management, concurrent symptoms, and really, if any of those are problematic, attending to those gradually with your team.

(37:41): So I think it's a long answer to say, I will be very much hoping that it gets better, but sometimes with fatigue, there can be what I call handoff causes of fatigue. So fatigue may develop because of, let's just say anemia or treatment side effects. And then it hands off to fatigue being caused by medication side effects and hands off to fatigue being caused then by lack of exercise and a loss of muscle mass. So there can be those handoff causes, and I really encourage people to be addressing gradually all of the different factors that I talked about in this presentation and making sure that one is attending to all of them, but setting priorities, because we can't do everything at once. Right? So I'd make sure that your team has done some of those other evals and then making sure that you're attending to the self-care things that I talked about. It's a great question.

(38:42): [Marsha Seligman] My transplant was four years ago and the fatigue persists today, but I push myself to do things. I tested and learned that I also developed active Epstein-Barr. Have you found any other transplant patients who are battling Epstein-Barr now?

(39:00): [Dr. Sandra Mitchell] Excellent question, and yes, the reactivation of Epstein-Barr virus infection is, I don't know if I say it's common post-transplant complication, but it's certainly one that does arise frequently. We call it reactivation because while you could get a first or primary Epstein-Barr infection, it usually develops because the virus reactivates in the body when we are immunosuppressed. So just like Epstein-Barr, and also the shingles virus and many other viruses, once we've had them once, our immune system may take care of it, but they hide out in our bodies, staying quiescent. So it certainly is a problem that arises and as we know, the Epstein-Barr virus, which also is responsible for what's called mononucleosis, that fatigue goes along with that. It's a prominent feature of it. I think again, that's certainly probably one of the major causes of your fatigue, but there could be others.


(40:16): And so it's important that you get that kind of monitoring. And then, really paying close attention to pacing and rest and sleep while at the same time, maintaining a program of exercise and physical activity and always trying to stay active. It may be helpful to be working with a physical therapist or a personal trainer periodically, and then also really attending to sleep and sleep disturbances. Very much with Epstein-Barr virus reactivation, helping people to not have lots of daytime napping can be a challenge. And so working out some ways that you can prevent yourself from daytime napping.

(41:10): [Marsha Seligman] The next question is, it has been impossible for me to stay asleep longer than 90 minutes at a time due to lupus side effects. I've also had an auto transplant six years ago. I get hot and clammy within one minute and 10 minutes later, I get very cold. My body temperature fluctuations are so extreme that I wake up six times per night. I get four hours of sporadic sleep per night. Sleep hygiene has not helped, melatonin, Lunesta and Xanax have not made a difference. What other class of sleep meds may help?

(41:47): [Dr. Sandra Mitchell] So this is an excellent question, and not knowing if this questioner is a man or a woman, because it's a little bit unclear given some of the symptoms that you're describing, whether these are hot flashes, for example, we definitely know that hot flashes interfere significantly with sleep and they can be a very difficult problem to manage. There is some evidence that the classes of medications called antidepressants can be helpful in controlling hot flashes and therefore improving sleep quality. Most of the sleep medications do not actually provide good sleep quality. And you mentioned that you've tried cognitive behavioral therapies and all of those different cognitive behavioral strategies. Keep on doing those, even when something is not immediately helpful, it's important that we take a layering approach.

(43:09): So keep on doing all of those approaches. Don't set them aside. But I think the two things that I would consider here would be seeing about being referred to a sleep medicine clinic and the benefits possibly of a sleep study. Because I would wonder if there were some underlying sleep disturbances there. And consider with your team, if this is from a woman and it is a hot flash situation, again, the consultation with the symptom management group to see about managing the hot flashes better because that will, many times, lead to better sleep quality.

(44:01): [Marsha Seligman] Dr. Mitchell, that was a female. So that information is very helpful. Thank you so much. The next person wants you to know what a great presentation this has been. And thank you for including a lot of different types of interventions for Omega-three supplementation. She would like to know if you have ever heard of the use of seaweed supplementation for Omega-three.

(44:29): [Dr. Sandra Mitchell] I have not. I don't have any knowledge of that. What I would say about Omega-three supplementation is that you definitely want to be pursuing that in consultation with your healthcare team. Omega-three supplementation, the Omega-three fatty acids thin out our blood and we can be susceptible to bleeding and bruising. You don't want to be taking those if you have any invasive procedures coming up. I don't know anything about the seaweed component of that, but if possible, I might defer to Sue and Marsha on this, you're welcome to offer them an email address and I can follow up with you with a brief email. But you can also really talk to your team about that. Unfortunately I can't comment more than that.

(45:29): [Marsha Seligman] Okay. The next person would like to offer a suggestion. I'm going to share this with everyone. I am very lucky that my local university offers Zoom classes for fitness and yoga. Also, my insurance includes silver sneakers, which has a lot of Zoom and live classes online. Patients should check all of these and see if they're offered. I did these during chemo, after transplant, and now at day 302, I am able to exercise five days a week, 60 minutes per day, both yoga and aerobics classes. Just wanted to offer those suggestions.

(46:08): [Dr. Sandra Mitchell] Thank you so much for those. And a really huge omission on my part for not having more about all of that because you're right. Those things have just exploded during the pandemic. Many bad side effects of the pandemic, but that's a good side effect. And there are also lots of great relaxation training things, so many things that are available on the internet to help with mindfulness-based stress reduction and relaxation training, even Tai Chi. So all of that. So yes, very great suggestions and great suggestions about silver sneakers and also that many health insurances finally are starting to realize that exercise is medicine. And so there may be opportunities to join various things as a result of your health insurance. And I think getting referrals to physical therapy and what-not, again, I think we're really starting to realize that that rehabilitation process is so critically important.

(47:18): [Marsha Seligman] The next person would like to know if you have any suggestions for the best medicine for improving short term memory.

(47:29): [Dr. Sandra Mitchell] Great question. I think, the wakefulness promoting agents and the, what we call psycho stimulants really methylphenidate., What I say to people is that those are basically like a Starbucks venti coffee, that they will produce that same kind of psycho stimulant effect. A lot of them have to just be trial and error to see both which medication and taken at what time of the day. So we never want people taking these psycho stimulants, typically we don't want them taking them after 12 noon because it will interfere with your sleep, but sometimes people need one dose in the morning and then another dose around 12 noon. And they then get the cognitive benefit through the rest of the day.

(48:24): So psycho stimulants are very much worth pursuing a trial, particularly when the fatigue is much more isolated cognitive fatigue and problems concentrating problems with memory. But the evidence for the psycho stimulants and wakefulness promoting agents is mixed. It's highly mixed actually, but there are individuals that do derive benefits. So I always think it's worth a trial. Just being aware that you may start to feel jittery, the heart can start to race and there can be problems with sleep. And so you just want to give it a real trial in close collaboration with your team.

(49:09): [Marsha Seligman] Dr. Mitchell, someone would like to ask you to repeat the name of the website prior to the questions. It was cancer and something, they would like for you to repeat the name of that website.

(49:23): [Dr. Sandra Mitchell] Let me just get to that one. Yes. So it's called, and I'm hoping that you're able to see that on the screen. And I will maybe have Sue, if there is a chat, maybe Sue or Marsha. Oh, there, I see it in the chat. Thank you. So that can be a great website to take a look at.

(49:55): [Marsha Seligman] Thank you for that. The next question is, I am 12 years from transplant, but continue to have extreme fatigue, three-or four- hour naps on a bad day, one-or two-hour naps on a good day, total sleep and rest per day, about 10 to 15 hours. I have learned several of the suggestions you have made by trial and error, but as time goes on, I'm exhausted managing my fatigue. I work around the house or outside by the clockwork, like if she was painting in the living room or gardening for 30 to 40 minutes a day. She's 70 years old and wants to know if you'd have any suggestions.

(50:39): [Dr. Sandra Mitchell] Well, I'm very sorry that you're experiencing that. And just really kudos to you for all the efforts you're doing to self-manage because this fatigue really is about that self-management so tremendous praise to you for all that you're doing to try to address that. I certainly have had some patients like what you're describing needing a lot more sleep, both nighttime sleep, as well as the naps. It sounds like the naps are not interfering with good quality nighttime sleep, but if they are, I think I would be doing everything I could to cut out those naps and to substitute some of the rest time with some of the relaxing activities that I described. It could be listening to music. It could be looking at pictures, if you don't feel like you really have the cognitive energy, having a few photo books of things that you find relaxing to look at, travel, or I have a really good one that I love that has all these pictures of dogs with people. And I just love looking at that. And it's quite restorative of fatigue just to take a look at that sometimes. So trying some of those strategies.

(52:11): I also would encourage you to be sure that you've been evaluated by your team for some of those underlying physiologic things we talked about, including that you've had an evaluation for any possible cardiac or pulmonary dysfunction, so that's heart and lungs, heart or lung dysfunction that could be contributing to fatigue. And you could also consider if you think your night-time sleep is perhaps not as good quality as what you think. And it's hard sometimes to tell if our night-time sleep is good quality, but one of the indicators is waking up not rested. So you think you've been asleep, but you wake up non rested and that sleep is not restorative to you, that would be an indication that there could be sleep problems. And in that situation, sleep medicine consults and possible sleep study, just make sure that there's not some of these other factors that are contributing.

(53:22): Unfortunately, sometimes we do experience more fatigue as we age, but I wouldn't let that be written off as the cause. I would be sure that all of those things have been sorted out. And then of course, just being sure that you are pursuing an exercise program that does include strength training, because we do lose muscle mass as we age and strength training is critical to that. And for many people, getting into strength training really does benefit from some sessions with someone who can help us learn how to do the kinds of strength training, including core training.

(54:04): [Marsha Seligman] The next question, is, any particular cytokine that are highly associated with fatigue? Many providers don't appear to be familiar with cytokine profiles. Is there a reference or a center to be able to point them to?

(54:21): [Dr. Sandra Mitchell] That's another great question. And I think our understanding of the way that cytokine profiles affect fatigue, it's incomplete and our cytokine profiles are also very complex because they represent the downstream thumbprint or fingerprint, if you will, of a whole complex inflammatory process that is going on in our bodies when we're healthy. And then you put layer on top of that, what we do and don't know about GVHD. I have actually published some stuff in this space around cytokine profiles. So if you want to offer your email address in some way to Sue and to Marsha, or be in touch with them afterwards, I'd be glad to give a couple of references to that.

(55:15): The issue is that we can't really treat those cytokines. We have drugs that will block cytokines, but in general, those will not actually improve fatigue. And they in general are a very blunt instrument and will lead to lots of other side effects. So we can't treat those cytokines in that manner. So it may not be a very actionable target quite honestly, but it's at least a way of understanding sometimes why fatigue may be worse, for example, during a GVHD flare. And it gives hope sometimes that things will get better as we, for example, can settle down the flare. But otherwise, we definitely know cytokines fuel that, but we don't have a lot that we can do as a directed treatment.

(56:05): That said, there is some evidence that mindfulness-based stress reduction, for example, and also yoga, favorably affect our pro-inflammatory cytokine profile. So I would encourage both of those interventions in anyone who's fatigued, mindfulness based stress reduction and yoga, both very important to consider. And there are some great yoga tapes, like videotapes and CDs, but also as the earlier questioner mentioned, there's some great Zoom yoga and there's chair yoga, which also is an outstanding approach.

(56:49): [Marsha Seligman] This will have to be our last question; we are running out of time. The next question is, how do you sleep when various types of pain from eye GVHD and musculoskeletal GVHD consistently interfere with sleep? Pain, sleep, pain, a vicious cycle. Do you have any suggestions?

(57:10): [Dr. Sandra Mitchell] Well, thank you for that question. And again, I'm very, very sorry that you're experiencing this. And you're right, it's a vicious cycle, because, actually, sleep deprivation increases pain perception. And then as you said, pain will obviously interfere with sleep. So that the management of eye pain and musculoskeletal GVHD-related pain are obviously going to be different. For the eye discomfort, there are many things that we can be doing about that. That includes punctual plugs and eye drops, directed treatment of the inflammatory process in the eye, bandage scleral lenses, et cetera. And it's too much to go into. There are some sessions in the conference about ocular GVHD. So seeing an ophthalmologist and talking with your team about this and getting assistance is going to be critically important. There's much we can do to bring that eye discomfort under control. And it's very concerning that that reflects highly active GVHD of the eye.

(58:15): For musculoskeletal concerns, again, directed GVHD therapy, if those are also causing pain during the day. But if it's mostly at night, you can talk with your team about approaches to manage both. If it's muscle cramping pain, there's some strategies we can use for that, or if it's just more of that gnawing, more continuous muscle pain and joint pains, managing those with bedtime narcotic medications can be very helpful in relieving the pain so that you can sleep. You're not using pain medications to sleep. You're using pain medications to relieve that musculoskeletal pain. But pain medications for eye pain, it will probably help, but I'm actually more concerned hearing about that, that some local directed therapies to the eye will be helpful.

(59:14): [Marsha Seligman] Closing. On behalf of BMT InfoNet and our partners, I'd like to thank you, Dr. Mitchell for your very helpful remarks. And thank you, the audience, for your excellent questions. Please contact BMT InfoNet if we can help you in any way. 

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