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Are You Tired? A Frank Discussion About Fatigue In Patients With Myelodysplastic Syndromes

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Published: Jul 5, 2011 11:12 am
Are You Tired? A Frank Discussion About Fatigue In Patients With Myelodysplastic Syndromes

Patients with myelodysplastic syndromes (MDS) often feel fatigued – tired, worn out, weary, bushed, or “out of gas.” Many people suffering from MDS find that they just don’t have the stamina they used to have.  Minor errands that patients once didn’t give a second thought to are now completely draining.  As a result, patients may begin to avoid potentially strenuous tasks and feel that they are not able to enjoy life like they once did.

So many of my patients with MDS tell me a similar story about how they were initially diagnosed: when they first began to experience fatigue, they attributed this symptom to “getting older,” until something strange happened that led to further testing (e.g., they began noticing bruises without trauma or purplish splotches on their skin) or else the symptoms of exhaustion finally got so severe that they just could not ignore it anymore.

Surveys show that fatigue is extremely common in people with MDS.  For example, in 2008, my colleagues and I studied 359 patients with MDS using validated questionnaires to measure quality of life and specific troublesome symptoms.  This study was performed on behalf of the MDS Foundation and published in Leukemia Research.  

We learned that by far the most common symptom experienced by people with all types of MDS was fatigue, usually to such an extent that it interfered with the patient’s ability to work or participate in normal activities. More than 90 percent of patients with MDS reported having debilitating fatigue.  Interestingly, there was no correlation between the degree of fatigue and a patient’s level of hemoglobin, the oxygen-carrying protein found in red blood cells.

It is a common misconception that fatigue in MDS is just due to anemia (low red blood cell counts), and that if anemia in MDS is corrected, the symptoms of tiredness will automatically get better. While some patients do feel better after getting red blood cell transfusions to raise their hemoglobin, other patients receive little or no symptomatic benefit from transfusions. That lack of correlation between hemoglobin level and symptoms is because MDS is more than just a form of anemia.

In patients with MDS, blood levels of cytokines – molecules that cells use to signal to one another – are often abnormally high, and these cytokines are well-known contributors to fatigue in a variety of conditions. Such cytokines include interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α), interleukin-8 (IL-8), interferon-gamma (IFN-γ), and others.  There is no reason to measure any of these cytokines in routine clinical care, and tests are not even available for most of them.  But their elevation does explain the fatigue associated with other disorders, and by extension MDS, too. 

For instance, patients with a bone marrow condition related to MDS called primary myelofibrosis often feel marked improvement in symptoms when they are treated with tumor necrosis factor-alpha inhibitors, such as Enbrel (etanercept) or thalidomide (Thalomid), or with inhibitors of the JAK2 tyrosine kinase that is commonly mutated and overactive in myelofibrosis, even when these treatments do not affect their blood counts.

In the 1990s, Procrit (epoetin) was frequently advertised as improving quality of life and relieving fatigue in patients with chemotherapy-associated anemia. Procrit, an erythropoiesis-stimulating agent that promotes red blood cell production by the bone marrow, has not been approved for MDS by the U.S. Food and Drug Administration (FDA), although this drug is still widely used to try to improve the hemoglobin in patients with lower-risk disease.

Unfortunately, the results of quality of life studies in patients with cancer-associated anemia treated with erythropoiesis-stimulating agents like Procrit or its cousin Aranesp (darbepoetin alfa) have been mixed, and the FDA ultimately clamped down on this kind of misleading advertising, which is why we do not see ads promoting the energy-boosting effects of Procrit on television or in magazines anymore.

Some patients with MDS-associated fatigue may benefit from treatment with stimulants of the central nervous system, such as methylphenidate (Ritalin), Provigil (modafinil), or Nuvigil (armodafinil). These agents are commonly used for patients with narcolepsy or certain other sleep disorders, and like high doses of caffeine, they can stimulate wakefulness.  However, none of these drugs are approved by the FDA for use in MDS, and no formal trials of their use in MDS patients have been published. 

In my own experience and that of my colleagues, results with these stimulants have been mixed. Many patients experience side effects such as agitation, difficulty falling asleep, or tremor. Some of my patients who have taken these medications tell me they feel much better, but others have told me these drugs just made them feel “wound up” or “like the lights are on upstairs, but the body downstairs isn’t ready to follow” (that is to say their mind was racing and alert, but they still could not bring themselves to get off the couch). 

One natural way of addressing fatigue that does seem to help for many patients is to stay active physically and to exercise as much as they feel comfortable exercising. Often people with severe fatigue find that the last thing in the world they feel like doing is to go take a brisk walk around the block.  However, making the effort does seem to make a difference over time to a patient’s level of stamina.

For some people, “being more active” may mean only a lap or two around the block or playing a few holes of golf without a cart, but for others who are already active, more strenuous aerobic exercise is usually feasible.  Of course, getting enough good quality sleep is also important, but most patients find they struggle instead with getting too much sleep and wish they could get by on less.

Ultimately, when we have better treatments available for MDS, fatigue associated with the disease will become a thing of the past.  But for right now, chronic exhaustion continues to be a very real problem for many patients, and fatigue needs to be a research priority.

Dr. David Steensma is a physician at the Dana-Farber Cancer Institute in Boston and an Associate Professor in the Department of Medicine at Harvard Medical School. His primary area of research focuses on myelodysplastic syndromes and related conditions.

Photo of Dr. David Steensma, physician at the Dana-Farber Cancer Institute and professor at Harvard Medical School.
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2 Comments »

  • Peggy Mills said:

    I want to thank the MDS Beacon and Dr. Steensma for this article about MDS and fatigue. It really helps me live within what I can do and push to exercise etc. but also know my limits and live within them.

    For those who are just learning how to live their lives a bit differently, I encourage you to read his article about fatigue. His article will help you so much.

    I`m just dealing with RA and blood drawn every three weeks. Many cells are dropping, but very slowly, and I have a good score. Looks as if I’m one who will not have to deal with leukemia, but dealing with immmune system compromised, fatigue, changes in body with hair, etc., and learning my lifestyle is greatly changed. Used to love traveling, but getting where good chair and book is a great place to be. Plus my artwork.

    I think one of the hardest to deal with is no energy after 2 or 3, and sometimes in bed by 5:30 pm, totally exhausted. Age plays a part, for sure, but the myelodysplasia is biggest part.

    I`m learning that it`s okay to just go to bed and rest. Also sleep more.

    My encouragement for others just learning about this condition is to just do what you can do and enjoy your life to the very best you can and thank God for it!

    God bless you for encouraging us all! Thank you!

    Pegg Mills

  • Ann Smith said:

    As a MDS patient who lived 15 years with no treatment and modestly low 10.0 hemoglobin. I think the age you are diagnosed at matters. I was 35. Most 60-year olds are not that active to begin with, and they are not “fit” by athletic standards.

    Normal athletes store more oxygen in their blood for the immediate use by muscle, later provoking the body to pant to bring new oxygen into the bloodstream through the lungs. I thought like the athlete I used to be about the problem of fatigue, I needed to build stamina. This is easier to do if your primary low cell count is not in the red cell lineage, because the red cells carry the oxygen around. Still by continuing to maintain and build stamina there is potential for improving your quality of life. Short bursts of any activity that produces breathlessness two times a day three to five times a week improve stamina.

    As my disease progressed I did not notice when it became “critical” because I had conditioned my body to make do with less. I only went in annually because while I had low-ish (60,000) platelets they seemed stable. Last year when I went in for my annual, my hemoglobin was 5, the only thing I had noticed was that I was out of breath climbing the stairs.

    I was lucky to have the time to raise my children. I was lucky to have a medically conservative doctor. I was lucky that in that time they began to unravel the mysteries of the cell and knew that decitabine [Dacogen] and ATRA might drive my incurable disease into remission (if only temporarily). I was lucky to find a slightly mismatched donor. I was lucky they raised the age for transplant in those fifteen years, I was lucky to survive the t-cell depleted transplant. At every step of the path, though, my determination to try to stay aerobically fit has improve my quality of life.

    Quality of life is nothing to joke about, knowing what you need and must have to be happy will help you direct your decisions. In an era where doctors will try anything to keep you alive, it is helpful to have some lines in the sand at your feet that say go no further.

    The reality with MDS is that most people have different rare diseases that yield the same result — eventually death either from slow attrition, or acute phase transition. Think about this, though, for just a minute. We are all going to die, the when of your death will always be in the future until it is finally now. Living is the journey to that moment.

    The doctors are very interested in this group of rare diseases only because they represent good basic science, studying how blood and immunity form from stem cells. As a patient, what you need to know is that you can buy time, but at a cost. The cost is often your quality of life.

    They used to call this disease smoldering leukemia. In many ways this is accurate. They can SEE what’s wrong in your bone marrow and they can measure what cytopenias you have. Now they can often identify a genetic variant of your disease. These things are interesting, but not necessarily meaningful.

    When I was first identified with MDS, the five year mortality was 80%. Now they have a more nuanced picture because they centrally collect data from around the world in set formats. This is a rare disease, fewer than 4,000 cases annually. Most rare diseases no one is studying. So be grateful you have MDS :-). Over time they are making progress. Too late for most of us, but they are still making progress.

    My motto on doing any drug is “is the gain worth the pain?”. Every drug has side effects. For us, the worst drug is the red cells. It took 17 units of other people’s gift of life to keep me alive through treatment and transplant.

    However, once you exceed your body’s natural ability to store iron, they don’t really know where it will go. People’s bodies have different limits. As an essential mineral, your body is normally quite good at picking up this nutrient and storing it, within normal limits. Once it is saturated, your body may start storing it places it doesn’t belong — typically the heart, lungs, kidneys, liver, and none of the “chelating” drugs work well, by then you often have organ damage. So it’s truly a pick your own death scenario. Die from lack of blood, or die from organ failure. I can figure out which one I prefer, particularly since in the hospital they have a machine that can replace temporarily any organ.

    Though I am a one year bone marrow transplant survivor, I know that the other older name for my disease was pernicious anemia. Do I really believe I am cured? Time will tell. In the meantime, I work on building stamina for all things, including my doctors :-) Knowing ” the score” as it stands now, Doctors 1, MDS 0, I am glad I traveled this path. But I am looking forward and already drawing new lines in the sand. Pernicious doesn’t sound like its going away without a fight. Meantime, my quality of life is pretty good. I even kind of went back to work 6 months post transplant.

    Wishing each of you a happy palm Sunday, with a view toward Easter.