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CLL Related Fatigue

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By Brian Koffman, MD

Fatigue Overview: Fatigue is one of the most common chronic lymphocytic leukemia symptoms and at the same time one of the most commonly overlooked and undertreated symptoms.

Cancer related fatigue (CRF) can be caused by the cancer itself, its treatment, and complications of both.

Our study of over 1,100 patients showed that 7 out of 10 CLL patients complained of fatigue at the time of diagnosis as did more than half during the “watch and wait” period.

CLL fatigue is different from simply being tired. Resting often won’t overcome the exhaustion. This fatigue can be more than an annoyance —it can be overwhelming.

Diagnosis: It is important to be sure you are dealing with simple fatigue. Let’s look at the “differential diagnosis.”

Fatigue can be related to but is clearly different from sleepiness that is resolved by getting more sleep. Patients sometimes confuse shortness of breath (dyspnea) with fatigue, but it is a separate problem that requires a different work-up and therapies.

Fatigue is a common symptom of problems other than CLL so it is important to rule out causes that may or may not be related to the CLL.A good work-up should check for significant anemia (mild anemia is usually well tolerated and doesn’t cause significant fatigue), thyroid issues, and blood chemistry to rule out liver, kidney and other diseases.

Anxiety, so common in CLL, chronic pain, occult infections, stress, depression and other chronic illnesses can contribute to fatigue. Your Health Care Providers (HCP) can help with some simple screening tests and often there are effective treatments once a specific diagnosis is made.

Treatment: Let’s say after an appropriate work-up, there is no clear cause found for your fatigue other than your chronic lymphocytic leukemia – what can be done?

Non-medical: The first step is to recognize how common this is and understand that there are reasons for it – you are not just being lazy. Don’t blame yourself.

CLL is a disease of the immune system. One theory for the fatigue is that in CLL, cytokines, enzymes that are released by white blood cells in response to inflammation, can reach high level that can lead to persistent fatigue. Being a cancer patient often means being chronically “inflamed.”

The next step is the basic advice any parent might give – eat well, stay hydrated, get enough restorative sleep and rest and pace your activities. Take breaks. Prioritize and delegate and be kind to yourself if you don’t complete everything on your “to-do” list.

Paradoxically, there is solid proof for cancer patients that the more you exercise the more energy you have, so if your HCP approves, do push yourself to exercise. Walking is often a good choice.

Medications: While there is no magic pill for fatigue, there are some effective “off label” options that you could discuss with your HCP. Armodafinil and modafinil are usually used to treat sleep related disorders; methylphenidate (Ritalin) is a controlled substance commonly used for ADD (Attention Deficit Disorder) and related issues. All of these may help CRF.

A more radical option: Ruxolitinib (Jakafi) is a powerful drug that is used to treat myelofibrosis that has been shown in clinical trials to improve CLL related fatigue. This should likely only be considered as part of a clinical trial.

Finally, sometimes the most effective way to treat the fatigue is to treat the root cause of it, the CLL itself. If the chronic lymphocytic leukemia burden is resulting in overwhelming fatigue, treating the CLL is a real option to be considered in consultation with your treatment team.

Summary: Talk with your HCP.  Talk to other patients in a support group. You are not alone. Fatigue is a common problem and there are options for help.


 Dr. Brian Koffman, a well-known doctor, educator and clinical professor turned patient has dedicated himself to teaching and helping the CLL community since his diagnosis in 2005. He serves as the medical director of the CLL Society Inc.

Originally published in The CLL Tribune Q3 2018.