Fatigue and Transplant: New Insights
July 13, 2020 Part of the Virtual Celebrating a Second Chance at Life Survivorship Symposium 2020
Presenter: Kenneth Miller MD, Associate Chief, Division of Hematology/Oncology, Tufts Medical Center
Presentation is 48 minutes with 8 minutes of Q&A. Download Speaker Slides
Summary: Chronic fatigue is a common complaint after a stem cell transplant. Learn what causes it and strategies you can use to manage it.
- Transplant-related fatigue is not just being tired. It is persistent physical and emotional exhaustion that does not improve with rest.
- Chronic fatigue interferes with cognitive, physical, and emotional functions, and is a frequent cause of poor quality of life after transplant.
- Exercise is a potent tool to fight transplant-cancer-related fatigue.
02:56 Cancer related fatigue is a distressing persistent sense of physical, emotional, and/or cognitive tiredness or exhaustion that is out of proportion to recent activity and interferes with the usual functioning of life
06:06 Risk factors for chronic fatigue after transplant include age (over 60), being female, sleeping too much or too little, total body irradiation (TBI) before transplant and pre-transplant fatigue or depression.
08:59 Physicians seldom ask patients whether they are experiencing chronic fatigue, and patients often do not report it, fearing it may be a sign of relapse.
21:42 New research suggests fatigue after cancer treatment may be caused by signals sent to the brain by pro-inflammatory cytokines that tell the brain that you are sick.
28:15 Targeted exercise to overcome physical deconditioning after transplant can relieve chronic fatigue.
31:43 Cognitive therapy helps patients organize their daily activities by recognizing when they have the most energy, and using assistive devices, if needed, to conserve energy.
33:41 Mindfulness and relaxation exercises have been shown to be effective treatments for fatigue.
34:49 Stimulant or alertness enhancing medication can be used intermittently before exercise or important activities to alleviate fatigue.
38:05 Yoga, sleep and maintaining a protein-rich diet can help improve fatigue.
38:58 A new system for measuring fatigue, developed by the National Comprehensive Cancer Network, can be useful in determining if a patient qualifies for disability benefits, due to fatigue.
Transcript of Presentation
00:00 [Moderator] Welcome to the workshop Fatigue and Transplant: New Insights. My name is Marla O'Keefe, and I will be your moderator today. It is my honor to introduce today's speaker, Dr. Kenneth Miller. Dr. Miller is the Associate Chief Hematology/Oncology at Tufts Medical Center and Professor of Medicine at Tufts University School of Medicine. He is a nationally recognized leader in blood cancers and stem cell transplantation, and Dr. Miller's research focuses on developing transplant regimens that have fewer toxicities. He is also interested in maintaining quality of life after transplant with a particular interest in helping patients manage fatigue. Please welcome Dr. Miller.
00:49 [Dr. Miller] Thank you, Marla. That was a very kind introduction. I'm going to be talking today about fatigue in transplant, which is a very common problem, in fact, poorly recognized by most physicians and poorly dealt with by most physicians. So, hopefully today in these 45 minutes you will understand the effects of fatigue and the quality of life following transplant, and in fact, it's a major cause of decrease in quality of life. Understand the causes of fatigue. It's not just because you're doing too much. Understand there are some possible new treatments, and understand what you, the patient, can do to decrease the effects of fatigue each day.
Fatigue and tiredness really are two different things, and while many patients' physicians use these terms intermittently, they really are not. Now, in tiredness, you complain of being weary. You have a lack of energy. There's a decreased endurance. A bad lecture, you would be bored. You're doing too much, but you tend to bounce back after you take a nap. And usually, tiredness is relieved by rest. Also, tiredness is generally temporary.
In contrast, patients who experience fatigue, well, they have less energy. They also feel less alert. Trouble concentrating. Trouble with social isolating. It's not related to the activities of fatigue. The more you do doesn't make it much worse, and rest does not improve it. There’re impaired sleep patterns, either too much sleep or not enough sleep, and fatigue can last for a long time and not just temporarily after the transplant. And uniquely, it's difficult to treat because it has so many symptoms.
What is cancer-related fatigue?
02:56 What is, really, cancer fatigue? And now, there are definitions which sort of help us to understand a little bit about fatigue and therefore, to complete studies. A distressing persistent sense of physical, emotional, and/or cognitive tiredness or exhaustion that is out of proportion to recent activity and interferes with the usual functioning of life. And again, you can see the subtleties between this and just being tired. This really interferes with both cognitive, physical, and emotional functions, and is one of the most distressing symptoms after not just transplants but many types of chemotherapy.
And so, fatigue findings. What do patients typically complain of? I mean, you have fatigue. Well, what do you notice? And patients complain and say, "I feel so weak. I'm tired all the time. Every part of my body's tired. I wake up tired. I need to rest all the time," but rest doesn't really make people feel better. And now, "I lack motivation, and I'm not interested. In others," it's the cognitive defects. "I have trouble sleeping at night, and I'm too tired to think clearly." Again, more of a cognitive function and decline associated with this chronic fatigue.
"I used to work." Patients who've had jobs and say, "I can't go work now. I used to have lots of interests. I used to socialize frequently, and I used to be interested in normal adult sexual relations," all of which are impacted by ongoing fatigue. It interferes with all of these aspects of the quality of life.
it is in fact, the most common symptom associated with cancer survivorship, and this is the percentage of patients looking at those three commonly perceived side effects associated with cancer and survivors, meaning patients who have completed therapy for any type of cancer including a transplant. 75% of patients continued to complain of fatigue as their major side effect, while pain was about 20%, and nausea was about 15%. And while so much focus has been on pain and nausea, there has been very little focus on treating and addressing the true issues of fatigue.
Risk factors for chronic fatigue after a stem cell transplant
05:22 And fatigue does have certain features which overlap with depression and it's really a multifactorial. So, the depression is your loss of interest in things, but that's not fatigue. A low energy is associated with fatigue, and poor sleep patterns or sleep hygiene is associated with fatigue. All these overlapping symptoms are part of separate diagnoses, but conceptually depression, tiredness, and poor sleep are really different than the kind of fatigue that patients perceive after undergoing a transplant.
06:06 So, what are the fatigue studies in transplant? Well, some of them are age related. Fatigue does increase in age, and its higher incidence in individuals over the age of 60. And when I began in transplants, the first paper I wrote was if you're above the age of 35, that was considered an old transplant, and now we go into the 70s and we're transplanting older and older patients. And therefore, fatigue becomes a greater issue.
It is more frequent in females, which is interesting since most of the side effects are more frequent in males. Now, are females asked to do more around the house? That may be a manifestation, but the fatigue is more common in woman than in man.
It correlates with sleep disturbances. Patients who either sleep too much or don't sleep enough. There's a poor sleep pattern. There's not the normal, "I go to sleep at a certain hour, and I sleep seven hours and wake up." Your sleep pattern is changed, and this frequently precedes the development of fatigue.
It's more frequent in individuals who receive total body radiation as part of a preparative regimen for a transplant. Why that occurs is not clear, but if a patient received that as an agent of their transplant regimen, seem to have long-lasting fatigue than those that seen other forms of treatment.
And the most disconcerting is that it does not necessarily improve with time. So, many of the side effects of chemotherapy post-transplant get better over time, and the farther you're away from it, things start to improve. Fatigue may not improve with time, and therefore, it needs to be addressed by both the physician and the patient.
And it is correlated with pre-transplanting symptoms. So, a patient comes into the transplant complaining of fatigue or depression or not being motivated, that those symptoms, in fact, continue after their transplant. Therefore, screening patients for fatigue before starting your transplant preparative regimen is important, and addressing fatigue, so the patients can start learning ways of dealing with fatigue before they start the transplant, is helpful in preventing fatigue later on.
Fatigue after transplant is under-reported
08:23 Now, physicians, do they ask about fatigue? Now, this is looking at a number of years in '90 and 2010. Percent of patients who complain of fatigue. In '90, very few patients complained of fatigue. They still had it; they just didn't complain. Now, in 2010, over 80% of patients note that they have a symptom of fatigue as part of their post-transplant course.
What questions do we ask? There were two studies looking at this. They are represented in these two colors. These are two separate studies in two separate individuals, and the first is "Did physicians ask you when you came to see them about the fatigue?" Regretfully only about 15% of patients in two separate studies were asked are you fatigued? Are you tired? The patients note fatigue when asked on this. Where the patients noted fatigue, you can see that 70 to 80% of patients yes, complained of fatigue. If you ask me, I really do have fatigue.
The quality of life was interfered by fatigue and physicians noted only a minority of patients had impact quality of life. But when you asked patients did the fatigue interfere with their quality of life, the range was between 70 and 60%. So, one, physicians don't ask enough, and patients do note it. Physicians don't think it contributes to impaired quality of life, but patients really feel that it does interfere with their quality of life.
10:20 Why patients don't ask about fatigue. The common complaint that you tell your physician about why you have ongoing fatigue. Well, many patients feel it's a sign of relapse because this is the first sign of their disease. They start complaining of fatigue and being tired. So, to complain of it, are they just saying they have a relapse and therefore scared to note it. "Doctor doesn't really know how to treat fatigue, so why do I need to bring this up in conversation if he or she is not going to do anything". Again, patients note that we have limited time, there are more important things to discuss than fatigue, so we don't bring it up, and there's not enough time to discuss it. And the last of the patients blame themselves. "Oh, it's my fault. I'm just not doing enough, and that's why I'm tired." Which clearly is not the case. So, these are reasons why patients don't really discuss fatigue with their patients. Also, patients want to help and please doctors, so when you ask, "How are you feeling?", you’re feeling fine. Patients generally like to make us feel better and therefore will give a positive answer.
Again, these are looking at patients with a source of information. Where do you get your information about the complications and the treatment to transplant? You ask the physician, that's really the minority of information in the physician's office. Majority of patients, in fact, between 80 and 90% get it from the internet. As you know, the internet is uncensored, anyone can write in the internet. Some of it is true and some of it is not true. The important point is you need to confirm this with a healthcare provider. Information on the internet may be provocative and may be a way of getting information, but it's not necessarily true.
Why don't we ask as physicians? It seems to be a common problem in all these studies. How come physicians don't ask patients why they're having fatigue. Well, it perceives sometimes not as a big problem. We have other things to discuss. More important things about post-transplant. How are you doing with other side-effects? How are the diseases doing? "I can't fix it, so let's not discuss this there is not much I can do about this." "It really isn't enough time. I only have 15 to 20 minutes for each visit and fatigue is a more complicated issue." And the last is, "I'm tired all the time too. So, I'm tired and your tired, there's not much to discuss here." That's actually why physicians don't ask the questions. It's this lack of accepted diagnostic criteria too. It's restricted drugs and there's no simple solution.
That is changing and it is becoming an accepted diagnostic criteria. The NCCN have criteria. Because of this more drugs have been approved. It is also insurance issues. They pay for insurance coverage.
Pre-transplant studies in patients with fatigue. One, it's age related, seeing patients who are over the age of 60. Baseline quality of life does matter. Again, as I noted females more than males. Emotional support which is really critical. One of the resources that you have that's supporting you prior, during and after the transplant, spouse, children, family. It's part of my transplant evaluation of who goes to transplant. What are the support mechanisms that help people get through this? It is really critical. It does correlate with sleep patterns and therefore that can be addressed prior to the transplant.
It is a negative aspect of income. Meaning that higher income individuals complain of more fatigue post-transplant. Why is not clear to be expected not be fatigued? They do less activity? That's not so clear. Many of these issues can be addressed prior to the transplant. Therefore the causes of fatigue - that's poor sleep habits, family activity, who's supporting you, depression - can all be addressed prior to coming into the transplant and therefore decrease the incidence of fatigue, but you need to talk to your physician. Okay.
In fact, when one looks at the quality of life in survivors of one year post-transplant, fatigue is the most common cause of the decrease in the quality of life. While patients are concerned about their appearance after the transplant, sexual relations and there is some degree of depression, it is overwhelming that the fatigue interferes with their quality of life for one year survivors.
What causes chronic fatigue after a stem cell transplant?
15:29 And there are certainly many causes of fatigue that are noted. They're disease related... melanemia, electrolyte abnormalities, low white blood count, being anemic, all those relate to causing fatigue.
And then there are some co-morbid conditions that patients walk in with fatigue... chronic lung disease, diabetes, heart failure, which all are associated with fatigue. There’re also treatments... Chemotherapy can be associated. Just the chemotherapy drugs themselves can be associated with fatigue. Surgery or hormonal therapy can cause fatigue. There’re side effects of therapy... nausea, vomiting, diarrhea or mucositis. Then there's the medications that we use to treat some of these symptoms which can cause fatigue. And the last is the psycho and social issues, financial concerns, sleep patterns... All of these are related to causing cancer related fatigue. In the past it was felt that this was majority... Any one of these was sufficient to cause fatigue.
And last which I added here is just being in the hospital. Hospitals are no place to really get sleep. As you know, people come take your blood pressure at four in the morning, there are noises over all night. And hospitals are really trying to address this, that patients can get some sleep in the hospital. But you as a patient, if you get hospitalized, you can ask... I don't need my blood pressure taken at four in the morning. You can dictate and somewhat adjust your time schedule, so you don't become overwhelmed with fatigue during your hospitalization.
17:17 There is now a scale and many of us have built this into our EMR. These are the parameters and you're given a scale that physicians will ask you on scale of one to 10, how much fatigue you're participating in. And this is important in part for insurance coverage, for getting disability insurance. Now there is a scale that is generally accepted across different hospitals.
Sleep disturbance can cause fatigue. Patients with mild sleep disorder after a transplant is very common. Severe sleep disturbances are seen about 20% of patients with fatigue and really needs to be addressed. Patients who either sleep too much or not sleep enough, have generally increases their incidents of fatigue.
Cancer-related fatigue is a positive feedback loop
18:07 Cancer related fatigue... It's also a positive feedback loop. So, fatigue makes you less physically active, deconditioned, loss of muscle mass and therefore you become weaker. Fatigue, you try to nap during the day, therefore have trouble sleeping at night. Therefore, have more daytime fatigue. Fatigue, you have less enjoyable activities. You become more isolated and depressed and lonely. All of these are positive. Medications that we use... The anti-nausea medication, the opioids for pain and other pain medications make you tired. Cancer treatments can cause fatigue... To neurohormonal mechanisms and we will talk more about that and the side effects of cancer treatment can make you fatigued.
Other disorders associated with chronic fatigue
18:56 This is a picture of the universe and this is where we are, an insignificant planet at the tip of this very large Milky Way galaxy. What is the big picture though? Now that we are all a part of this universe, and this is where Earth is. But the big picture in fatigue is we're learning that it's not those simple things that happen during the transplant. But this is a basic mechanism of how our organism survives.
Disorders with fatigue with common similar features... So, what other disorders have fatigue? Well one, aging is associated with fatigue in part. As we get older, we do get tired. And that line is sometimes difficult to understand. Age is not linear. We don't age the same amount from 61 to 62. In fact, we age by waves from 60 to 65, or 65 to 75. It doesn't happen just by each year. And therefore, there's something to be done for that. It's not as if each year that you add to your life you become more fatigued. No. Aging is one of the causes of fatigue. It doesn't happen immediately.
The next is this concept of frailty. Cancer, we see people start losing weight, losing muscle mass, and falling at home, which is a major issue. It is associated with the ongoing fatigue. And therefore, strengthening muscles and looking at exercises that specifically improve your balance to prevent falls and maintain your muscle mass are very important.
On the certain disorders that are also associated with fatigue, and these are models that we have learned from, are why patients have fatigue. MS is one of them, multiple sclerosis... and it's been shown that this is due to an inflammatory cytokine. Something produced by the disease and how it relates to us. You generally see it between three and six months when you treat with an anti-cytokine in this disorder, fatigue starts improving at about 12 months. Again, another model for disease.
Myasthenia gravis... again, a disease. A non-malignancy associated with fatigue. Patients who have post-stroke have ongoing fatigue. Again, the mechanisms are not related to chemotherapy. Patients with severe heart failure... And then there's this group of blood disorders, of blood cancers, where they are associated with fatigue before the diagnosis is even made, before treatment is started. The question is why?
Pro-inflammatory cytokines may trigger "sickness behavior" and chronic fatigue after transplant
21:42 Oh, the cancer related fatigue one... The effects of treatment anemia, low white blood count... They all cause this fatigue and we attribute so many of the symptoms to that. There's decreased appetite and nutrition goes down, patients lose weight, and you lose muscle mass, and that contributes to fatigue. There's an electrolyte abnormalities, medication side effects, symptoms of nausea, impaired sleep, inactivity because you don't feel well... And then there's psychological distress of depression, anxiety, and financial concerns about being ill. And these do all cause fatigue in the background, but there's something more to it. It has to do with these pro-inflammatory cytokine-mediated effects. that the body in response, or after the transplant, it secretes these pro-inflammatory messengers that the body responds to.
This is the new concept of fatigue. And while all the things prior to this are associated with the development of fatigue, our new concept of fatigue is that this cancer therapy, this infection, this tissue trauma of cancer therapies, all these activate this pro-group of pro-inflammatory cytokines which produces fatigue. And while physical symptoms and medical conditions weigh in, and psychological, it is this ongoing inflammation associated with either disease or the treatment, or the events post-treatment, that are secreted by the body to which the brain reacts.
Here's the picture of the new concepts of fatigue. Each of these organs with inflammation, can be associated fatigue, graft-versus-host disease, secrete inflammatory cytokines which respond to receptors in the brain. And these receptors in the brain sense this signal from the body, and you see the same signals in patients with heart failure. Same signals in patients with cirrhosis, or neurologic defects. You see the same signals in patients without cancer. And the brain interprets this as a sickness behavior, and that's really the term that's used. The brain interprets this release of cytokine that the individual is sick and therefore starts producing the symptoms as associated fatigue. Even though the patient may not be sick, these are signals are being sent and that's how the brain interprets it.
The sickness behavior is really the signals to the brain to sense that fatigue is how it should respond. It causes sleep disturbance, decreased or increased. It impairs sleep patterns. It causes depression. It causes a decrease in appetite, this sickness behavior.
The causes of fatigue the current theories... one is the activation of the pro-inflammatory cytokines. The cytokines, these messengers that are secreted by the body that interact with our brains to say that you're sick. It's a sickness behavior. Fatigue, it disturbs sleep, depression, muscle strength and movement. It's increased expression of inflammatory related diseases which are usually secondary to these messengers. There’re abnormalities of energy metabolism that happen with secretion of these cytokines that would therefore require muscles to work harder to do the same thing. Which means that if you exercise you have to work harder to get stronger. And fatigue in part, may be patient related as some patients are more sensitive to the effects of fatigue, or they have a higher instance of cytokines. And it may be treatment related in that certain drugs we use produce these signals to the brain more than others. This area is now undergoing constant investigation.
Factors that contribute to chronic fatigue after a stem cell transplant
25:53 Fatigue and transplant... It can occur both early and late after transplant. Fatigue does impair the quality of life. It increases incidents in patients with graft versus host disease, which is associated with chronic ongoing inflammation. It occurs in both the auto and the allogeneic transplants. It is age related as I alluded to, seen in older people, and it may last for years or may not go away at all. And now there is a scoring system which allows patients to at least get some benefits. It's called the FACT-F. So, your physician should give you a score of fatigue and therefore you can compare visits or different treatments.
We'll look at the cancer as it is related fatigue. There's a cancer and it's treatment. There’re changes in the immune system, behavior changes, genetic factors all result in this concept of chronic inflammation and release of these inflammatory cytokines which the brain interprets as a sickness syndrome. Therefore, to overcome this you need to sort of interrupt this pattern of the brain.
Treatments for chronic fatigue that work after a stem cell transplant
27:10 So, what are treatment that works? Most studies are really focused on exercise. Exercise does interrupt this fatigue, it sends different signals to the brain, sometimes increases your muscle strength, and therefore makes the work of activity less. There’re psychological effects. Depression is also associated with ongoing inflammation, therefore having a therapist or being involved in groups, or having a support mechanism or people around you do help. There are other activities. These are non-pharmacological activities which variously have been shown to be effective. Yoga, medication, adequate nutrition, good protein intake, improving your sleep pattern, having family around so you're not isolated, all of these can be treatments for fatigue. Physical activity, psychological interventions, and then there's the pharmacology I want to talk about the drugs, and complementary medicine.
Exercise to reverse deconditioning after transplant can help with chronic fatigue
28:15 So, studies in fatigue... One, physical deconditioning. Strength training was helping, in fact obtaining prior to entering the transplant unit and during the transplant unit was associated with decreased fatigue and maintaining muscle strength. And it's targeted physical therapy... You target certain muscle groups, the legs for walking, the arms for patients who are weak, and you combine this with cognitive behavioral therapy, meaning that you combine this with a behavioral therapy... That I'm going to accept that I am fatigued a certain part of the day, and I am going to reschedule my day according to what time of day is best. Aerobic, meaning exercise, and non-aerobic with muscle strength together are better. Increased muscle mass helps and increased cardiovascular helps. Every other day for 10 minutes seems to be all that's needed, although it's quoted in literature that you have to do 150 minutes a week, that's very difficult.
Supervised is better. You're either supervised by your trainer, supervised by a video, supervised by a friend, that you complete the exercise that you planned in each of the muscle groups. And while not every study has shown that exercise does help, in the majority studies exercise does ameliorate some of the influences of fatigue and also makes muscles stronger so you feel less fatigue when you do certain activities. Why does exercise work? Well it optimizes the function of multiple systems; it changes the muscle biochemistry. As alluded to, with all the inflammatory cytokines, muscles require greater energy to do what they do before. With exercising you change that. So, therefore they don't require more energy. It's delays muscle fatigue, therefore you sense that you are less tired even though you still may have all those other factors. It decreases the perception and signs of shortness of breath. It decreases depression and anxiety associated with exercise treatment for patients who feel very depressed. And there is also cognitive behavior changes associated with it that you are in fact charge of your care.
When to begin is somewhat controversial. This was study out of Europe when they started fatigue when patients were in the transplant room. Patients were randomized in one to one to begin an exercise program prior to day 100. 30 minutes of aerobics five days a week to reach a maximum of 40 to 60% of the heart rate, not very high, and patients in the exercise group noted less fatigue, an increased cognitive function and an improved quality of life when they measured everyone at day 100, in the hospital and supervised exercise program. So, even during the transplant, while chemotherapy is going in, there are side effects from the treatment, exercise during this period had a profound effect even up until day 100 and decreased the long-term effects of fatigue.
Cognitive behavioral therapy can help patients manage chronic fatigue after transplant
31:43 Cognitive behavior... What are the strategies for that? You should target your physical therapy to specific muscle groups, the legs to prevent falling, balance, and arm strength. Therapy should be targeted, not just general, but should be targeted to specific muscle groups.
There's a change in illness related cognition, adaptive strategies. Patients should not set themselves up to fail. In my own division, walking from the downstairs elevator to see me is about a half mile long walk. There's nothing wrong in using wheelchairs, lifts or oxygen. Nothing wrong in using carts to help push things. You should do things to help yourself and not increase your muscle output at times when you don't need it. That's part of this cognitive therapy that... I accept that there is a certain level of fatigue and I'm going to do what I can to decrease it.
Set reasonable activity goals when living with chronic fatigue after transplant
32:20 Motivation is very critical and family support is very helpful, and you want to maintain social contacts, which increases patient's cognitive function, again, a big problem with fatigue. And the last is don't set patients up to fail. Four tests in one day is really too much. Walking from clinic to clinic may be too much. If there's an activity during the day that's important, you want to make sure that you reserve that activity for the time when you are not fatigued so you can enjoy it. You need to plan your day, so you work around this concept of fatigue. Planning the day is very critical, especially for things that you enjoy. As John Lennon said, "Reality leaves a lot to the imagination." As you plan your day, determine how the outcome will be.
Mind-Body practices, also called mindfulness, can reduce fatigue.
33:41 Actually, the mind and body practices reduce fatigue. Mindfulness it's called. That is a non-physical activity to reduce fatigue, and this is a large study of almost 5000 patients, where they taught them mindfulness and relaxation reduces response, and they sort of decrease instances of fatigue. Mindfulness is really defined as bringing one's complete attention to the present moment to experience in an accepting way. That means you're going to think about what you have now, and accepting that is in part, and moving on. It helps people become more aware of their automatic reactions to fatigue, like I can't do that. That's too much for me. It's a new approach and you don't need to do it all day, but it focuses patients' awareness in the present moment and helps experience less distress. This new concept of mindfulness as we get old, out practicing this mindfulness, is really very important to maintain your sense of equilibrium and avoid getting old.
Alertness enhancing medications can provide temporary help with chronic fatigue after transplant
34:49 Alertness enhancing agents. These are the stimulants. And across the board the stimulants do have issues. Anti-depressants really don't work, while they’re frequently given out. Caffeine as a stimulant has a limited benefit. And there are a number of stimulants, and the most widely used is probably Ritalin, given out to patients. There is a short acting and a long acting form. It does have an addictive potential. Intermittent use is better. I generally tell my patients to use this before you want to do something that's fun. If there's a social gathering, you'll take the pills half and hour before going out. It will give you energy for that. If you take it day in and day out, they become really less effective. You can use this to take before exercise, so you can exercise completely.
So, there really isn't one scheduled dosing you should stick to but should use these as an agent to allow you to do activities during the day. Studies clearly suggest there's a benefit for these drugs. There are these side effects and some of them are doses very patient specific. Some patients are very sensitive to the side effects and some people need a larger dose. It is a controlled substance; therefore physicians have to fill out a lot of paperwork to get this drug, however, it really does help taking it intermittently before doing specific activities. The chronic use of stimulants all day will not overcome fatigue every day.
Then there's a new class of drugs, alertness enhancing agents. These are given to patients who have exceptive sleep issues, narcolepsy, patients who have to work night shifts, these are given to airline pilots who have to fly all night. They're not stimulants, they just make you not fatigued. There are less highs and lows, patients are less jittery, but they last longer. It has a less addictive potential. Insomnia, however, is an issue because they last long. The two drugs are Provigil and Nuvigil. They are marketed to agents on Wall Street - why sleep if you don't sleep you can make more money? The Wall Street people got their hands slapped, that's not an indication for the drug, but they're interesting if you take them intermittently, again to the overcome the sense of fatigue. If you take them every day they seem to work less well. Once a day with less drug dependence, they do hang around a long time and therefore some patients have complained of insomnia with it. There is less side effect profile but that was still an issue, and what dose to use is somewhat unclear since they were not developed to treat cancer related fatigue.
I use it for my patients that are going to go out for a long day activity where Ritalin only last four hours at most, so it's better then to give them more energy and less fatigue during it, but if you take it every day it loses it's effectiveness.
Complementary therapies, such as yoga, can help manage chronic fatigue.
38:05 A complementary treatment. Yoga does help and studies have shown that focusing on yoga. Now, Yoga is available by television with someone to guide you through it. The role of acupuncture is still somewhat unclear. There's all kinds of other therapies, relational therapy, unclear. Sleep hygiene meaning better sleep patterns is really critical. How we all get ready for sleep is critical. Avoid computers, turn off the TV, keep the lights low. All this should be practiced so your body adjusts to the concept that sleep is the next thing that it is going to do. Maintaining an active diet with protein to avoid [loss of] muscle mass is also critical. Dietary supplements do help on that so that you don't lose protein and therefore lose muscle mass.
New scoring instruments and coding guidelines for chronic fatigue can help patients get disability and clinicians get reimbursed for treating it.
38:58 So there are new instruments that measure fatigue, with better studies really to come. Evaluating energy, evaluating mood, intellectual capacity, family life, sexual relations, professional life to be able to go back, what you do in your leisure activity and all these relate to quality of life issues. A physician should note this because it is now becoming a source of disability payments if you have fatigue related to your prior therapy. With this system, it is now generally more accepted. And, the fact that there is a scoring system from zero, you have no symptoms, to 10, they are the worst symptoms of fatigue. This was developed by the National Comprehensive Cancer Network and therefore is accepted by most hospital.
There is now a proposed IC10 guidelines, therefore treating fatigue is now therefore reimbursed by insurance companies. There are 10 items that you should note and this is more for physicians of what they should note in their chart, if you want to document that the patient has cancer or transplant related fatigue.
40:11 Standard of care in cancer-related fatigue... Well, a multi-disciplinary approach really does work and someone to do exercise. Someone to help with diet. Someone to make sure that there is family support. All these relate to fatigue and each one does help. You want to educate and train health care professionals in fatigue management and recognition. You want to use fatigue in your clinical health outcomes. In our institution, there is already an electronic medical record that has a fatigue score that is recorded on each visit. Medical care contracts should include reimbursement and pay for treatments associated with fatigue that we have system that covering it, and this is happening in health care.
40:55 Disability insurance is now beginning to look at fatigue as a recurrent symptom of why patients can't go back to work. And rehabilitation should begin with the diagnosis. Therefore, as the earlier study, the earlier you address some the symptoms associated with fatigue, muscle weakness, sleep hygiene, social contacts, ongoing inflammation, the less fatigue that will be post following the transplant.
So, ICD-10 is a diagnostic code so patients and physicians can get paid. It allows you to prescribe these narcotic medications and controlled substances. It may help in disability payments and obtain services and payments, and trainers and visiting people to your house to help. So, by having this coding system gives you great benefits.
Steps patients can take to manage chronic fatigue after a stem cell transplant
41:53 What are the preventive strategies? Well, you need to really schedule your day. If there is an activity during the day that you want to enjoy that's the time of the day that you should either take your medicine or not do other activities that will make you more fatigued. Quality of life and doing things help. You need to plan your activities. A day full of activities may be too much, you need to plan what you can do.
Medication timing, review medications... You want to avoid taking steroids in the evening. That will keep patients up and interfere with steroids. You want avoid taking diuretics, it will make you urinate at night. Getting up to go to the bathroom and getting back to sleep for some patients could be very difficult. And, you want to avoid daytime sedation medications that make you feel tired during the day so you're napping. These all contribute to the ongoing fatigue.
Another thing it's difficult to catch up on loss of sleep. Patients in the hospital for two days, it generally takes two to three days of sleep to catch up for those two to three days of being in the hospital. It is not catching up in just one night. Sleep hygiene is critical. You need to plan what you do before going to sleep. Diet is important and hospitals, as I alluded to before, are no place to sleep.
Individualized Approach to Fatigue Management After Transplant
43:25 In essence, there is like in a puzzle no one answer, no one side that fits all. You really need to think of the individual of the patient. The patient must tell us what symptoms bother them the most in fatigue. And, address each of these therapies to help to maintain adequate muscle strength. To make sure they enjoy the quality of life. To make sure they enjoy the day. Some patients do well with pharmacology, others do well with non-traditional medicine.
How to talk to your doctor about fatigue after transplant
43:59 So what should the patient do? Well, talk to your healthcare provider. Tell your physician... I have fatigue... It's interfering with the quality of my life and what can we do about it? You need to ask for help. It's not your fault that you have fatigue and it's not a sign of failure and it's not a sign of relapse. You need to discuss the medications of fatigue. Do any of these drugs I am taking contribute to the fatigue? Or is the scheduling I am taking contribute to the fatigue. These are common causes. You need to discuss structured exercise. How can I put this in my schedule, and who can help me and show me what exercises to do? Review sleep patterns. Sleep hygiene. How many hours do you sleep? How do you prepare for bed? What do you do to make sure that you do go to sleep? It does take time and planning. It sounds somewhat paradoxical, but overcoming the ongoing fatigue requires a conscious planning your days activities.
In summary, cancer related fatigue is really the most common symptoms of cancer survivors and transplant survivors note. 70 to 90% of patients, with any kind of treatment experience ongoing fatigue. It can last for months, for years after treatment and may be delayed on onset. Patient's perception of fatigue is the most distressing symptom. More than nausea or vomiting, they rarely tell their physician. The physician rarely asks. It is under-reported as I mentioned before, under-diagnosed and therefore under-treated. In part, there now are treatments to prevent it that need to be addressed before a patient comes in for transplant, and needs to be maintained after the transplant. Quality of life is critical and fatigue really does impact patients quality of life at what they can do and their ability to go back to work.
Sir William Osler, this is his years, is really the father of modern day medicine. Before Osler founded John's Hopkins School of Medicine, everything was really very much a trade. He wrote in fact the first textbook of medicine and said medicine really is a science. There's a body of knowledge that could be taught. He was the father of modern day medicine and died at the age of 70. He was a visiting professor at Oxford England, and in fact, his comments were the practice of medicine is an art, not a trade. "A calling from your heart and your head. Least we forget amid the racket of practice, few of us have the chance to warm both our hearts and hands at the fire of life, for our work is not an easy one of physicians. We must not forget to listen to the patients." One of the classic quotes that diagnosis can be made by listening to your patients. As for the history, it is well documented and I have included this because in the Spanish Flu influenza epidemic, which is now becoming very similar to the epidemic that we're all in, 1918 to 1919, Osler was a visiting professor at Oxford for two months. He caught the flu, which was complicated by pneumonia, but he died of influenza as a visiting professor. If he had never gone to Oxford to be a visiting professor and stayed at John's Hopkins, perhaps he wouldn't have gotten the flu. It's certainly changed the clinical course of medicine by having one of the great men in medicine die of influenza. We must remember 1918, 1919, the world changed for all of us, much like it is happening now. I think that's my last slide. Yes, thank you.
Question and Answer Period
48:10 [Moderator] Thank you so much Dr. Miller. That was an excellent presentation. We will now take some questions, and as a reminder if you have a questions, please type it into the chat box on the left side of your screen.
Our first question is, I know fatigue is bad following treatment and transplant, but how long is it okay for fatigue to still be a problem? I am three years out and I am still dealing with it daily.
48:36 [Dr. Miller] This is not uncommon. Fatigue can last for years after the transplant. While for some people it occurs right after the transplant, just for the treatment, most patients experience fatigue much like the patients asking three, five years afterwards. Therefore you need to start looking at ways to decrease your fatigue because it is not going to go away on its own.
49:02 [Moderator] Okay. Thank you. Next question is you mentioned aging is associated with fatigue. I have heard that having a transplant ages you ten or more years. Is that true?
49:14 [Dr. Miller] There is two lines in there. As we get older, fatigue is part of aging, however, it's not linear so patients who are 60, and individuals who are 65 are not necessarily more fatigued. It doesn't happen a year at a time. It depends upon your activity, who you are. But, as we get older fatigue is more of an issue. And the aging associated with the transplant is really not so clear. There are signs of aging associated. Skin does get older, there are some cataracts that occur earlier. Some of the manifestations of aging are accelerated. But, it's not really defined 10 years associated with it. And, patients that maintain more activity, maintain muscles strength, keep on good eating habits and really change in life style, the overall effect in increasing aging, now patients with transplants have just about normal life span of an age match control.
50:24 [Moderator] Thank you. What is your thinking regarding the use of melatonin post-transplant to help with sleep at night?
50:34 [Dr. Miller] For some patients they like it, it works. Again, it doesn't seem to be associated in the way of side effects. It does help regular body sleep wake cycles. It's not addictive, so it's one of the substances I recommend and you can combine it with other things. The other thing is the continued use of melatonin is people get used to it. So having the melatonin or any sleep inducing holiday allows these drugs to be active for a longer period of time because you can go back and use them again if they worked before.
51:13 [Moderator] Thank you. Next question. I try not to take any prescription drugs unless absolutely necessary. How severe are the side effects of drugs like Ritalin and are there any natural or non-prescription options that could provide benefits?
51:30 [Dr. Miller] So, Ritalin does have some side effects. Some patients... It is an age related side effect. All the patients say they feel more jittery on it, more nervous on it. So, others find it even a small dose does help them if they want to go to a movie, if they want to exercise, if they want help to get them through a small event. Taking it daily to overcome fatigue, the body generally gets used to it.
Are there any other activities... exercise have been universally used as the baseline for helping fatigue. Your body does secrete certain cytokines and it tries to overcome this sickness induced. Building muscle mass makes you stronger. The muscle mass you have, the less energy muscles have to work. The more muscle mass you have makes breathing easier.
So, exercise is important. Mindfulness, yoga. All those are alternate forms of therapy which in some randomized trials, again this is always very difficult because patients have to do it, hard to control, but have shown a benefit. Therefore, not all my patients are on Ritalin or drugs to decrease fatigue at all. I think probably it's a minority of patients who take, but the use of exercise, mindfulness, yoga, things aiming to improve one's quality of life really do help with fatigue and specifically with exercise, you may not feel as tired, your muscles don't so you don't feel as tired. It's really the improvement in quality of life and overall the benefit of non-pharmacological agents seems to be better than the use of drugs though the two together should not be frowned upon. It allows you to start a program and you can always stop the drug.
53:29 [Moderator] Thank you. Next question. I had my transplant almost three years ago. I'm much stronger now. Sometimes when I overdo it, doing manual labor or playing with my four young kids, I crash hard for a couple of days. Is that normal?
53:46 [Dr. Miller] That's the planning your day. As we do get older, we do crash for a few days. It's critical to sense when you have had enough. Using aids to help you at that time, there is no benefit from doing too much and therefore feeling fatigue and crashing for two to three days. Patients, individuals need to understand what their limits are, and if it limits means I only get to do it half hour now and then I'm going to take it easy for two hours and go back, that's what they should do. You should plan your day so you don't wear yourself out, so you don't lose two more days. That is really critical.
54:34 [Moderator] Next question. How do you sleep when various types of pain from eye GVHD and muscular skeletal GVHD constantly interfere with sleep? Pain, sleep, pain... a vicious cycle. What is your suggestion?
54:51 [Dr. Miller] Well, this is hard. Pain tends to be worse at night that during the day. Less distractions than during the day. You should plan for sleep. And, if you are going to take your pain medication, you should take it at night so you are not in pain at night so you can sleep. Sleep hygiene is really critical. You should take medicines that are a little longer lasting, and if you need to take a medicine in the middle of the night when you wake up in pain, you should not have fear about taking it. The sleep is so critical. It's really planning your sleep, so you have the medicines on board so you don't feel uncomfortable and you can sleep. If it means taking extra drugs in the middle of the night, that's fine. Sleep is really critical for overcoming some of the fatigue. Moreover, the lack of sleep, the sensing of pain really does increase. There is very little on the way of distractions. Trying to fall asleep when you have pain, the pain really seems much worse.
55:53 [Moderator] Okay, this is going to be our last question. We're running out of time. Can this kind of fatigue be confused with anemia from low red blood counts caused by medication?
56:06 [Dr. Miller] Yes. In fact, as physicians we love to say "oh this is anemia. That I can fix." Patients who are anemic, raising their red cell count does help and overcomes some of the effects of fatigue, does supply more oxygen to tissue, but the majority of patients who complain of fatigue, it's not due to their anemia. Those are the correctable ones and things that you can correct easily. You should make sure that your physician tests that you're not anemic, thyroids not off, that you're not deficient in certain vitamins. Those are easy to correct and should be evaluated.
56:47 [Moderator] Thank you Dr. Miller. On behalf of BMT InfoNet and our partners, I would like to thank Dr. Miller for his very helpful remarks and thank you the audience for your excellent questions.
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