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Hairy Cell Leukemia

What Is It, How Common Is It, and More

Author: Corinne Tarantino, MPH

Editors: Alyssa Haag, Ian Mannarino, MD, MBA

Illustrator: Jillian Dunbar

Copyeditor: Joy Mapes


What is hairy cell leukemia?

Hairy cell leukemia is a rare, chronic (long-term), cancer characterized by an overproduction of hairy-looking white blood cells. Leukemias are a group of cancers that affect the blood and bone marrow, which is the spongy tissue inside of bones where blood cells form, while white blood cells are part of the immune system, helping fight infections and foreign invaders, like bacteria and viruses. In the case of hairy cell leukemia, there is increased production of non-functional, abnormally shaped lymphocytes, one of the main groups of white blood cells. These abnormally shaped lymphocytes have a characteristic “hairy” appearance because their cytoplasm, the clear fluid inside of the cell, projects outward. 

How common is hairy cell leukemia?

Hairy cell leukemia is rare, with about 600-800 new cases in the United States each year. Additionally, hairy cell leukemia makes up only 1-2% of all adult leukemias.

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What causes hairy cell leukemia?

Genetic mutation is likely the most common cause of hairy cell leukemia, but this has yet to be confirmed. It has been discovered, however, that most people with hairy cell leukemia have a mutation in their BRAF gene. BRAF is a gene that provides instructions for making the BRAF protein, which then helps the cell know when to replicate. The mutation causes the protein to become constantly active, leading to increased cell division. Uncontrolled cell division allows for more mutations to occur, further altering the already prolific cancer cells. 

In hairy cell leukemia, the genetic mutation occurs in blood stem cells of the bone marrow called hematopoietic stem cells. These cells are able to differentiate into white blood cells, red blood cells, and platelets. With hairy cell leukemia, the hematopoietic stem cells overproduce lymphocytes, thereby decreasing the space available in the bone marrow for other types of blood cells to be produced. Additionally, the leukemic cells may produce substances that prevent stem cell differentiation into any other cell types.

Other causes and risk factors for hairy cell leukemia are currently unknown. Regardless, this cancer most commonly affects adults with a median age of 55, and it is almost never seen in children. According to collected data, males are disproportionately affected compared to females, at a ratio of about 4 to 1.

What are the symptoms of hairy cell leukemia?

The general symptoms of hairy cell leukemia include extreme tiredness, frequent infections, general weakness, and unexplained weight loss. Symptoms often develop slowly over several years and typically arise as a result of low levels of all blood cells in the body (i.e., pancytopenia). Decreased production of red blood cells (i.e., anemia) can cause extreme tiredness, general weakness, and shortness of breath. A reduction of neutrophils (i.e., neutropenia) and monocytes (i.e., monocytopenia), which are two groups of white blood cells, can weaken the body's immune response and consequently result in frequent infections and fevers. Individuals with hairy cell leukemia are thus more susceptible to uncommon infections, such as from mycobacteria, a group of bacterial infections that includes tuberculosis. Additionally, low numbers of platelets (i.e., thrombocytopenia) may make the individual more susceptible to bruising or bleeding because platelets are critical to blood clotting.

Usually, the leukemia cells collect inside the spleen, causing it to increase in size. This can produce additional symptoms, such as pain below the ribs. In about half of people with hairy cell leukemia, cancer cells will accumulate in the liver, often followed by yellowing of the skin and eyes, nausea, and loss of appetite. Occasionally, the leukemia cells also collect in the lymph nodes, resulting in painless lumps in the neck, underarm, stomach, or groin. 

How is hairy cell leukemia diagnosed?

Diagnosis for hairy cell leukemia is based upon a clinical examination, which includes a review of the individual's signs and symptoms, medical history, physical examination, and laboratory findings. If hairy cell leukemia is suspected, initial blood tests are typically conducted, including a complete blood count (CBC) to define the proportion of the individual’s blood cell types and identify if pancytopenia is present. Other blood tests may include a peripheral blood smear, in which the blood is examined under a microscope to look for “hairy” cells, and blood chemistry studies, which examine the function of different organs (e.g., liver, kidney).

If initial blood testing indicates hairy cell leukemia, additional diagnostic tests may be performed to confirm the diagnosis. Usually, a bone marrow aspiration is conducted. This requires a large needle to be inserted into the upper part of the hip bone to withdraw a small amount of the fluid part of the bone marrow. With hairy cell leukemia, a “dry tap,” in which no bone marrow comes out during aspiration, is common. When a dry tap occurs, a bone marrow biopsy is conducted, with the needle removing a piece of the solid bone with the fluid portion still inside so the fluid can then be examined. 

Frequently, further specialized lab tests are then conducted using the blood and bone marrow samples. Immunophenotyping identifies the antigens, or the various proteins located on the surface of the cells, which can assist with diagnosis. Typically, leukemic cells have the antigens CD11c, CD19, CD20, CD22, CD25, CD103, and CD123 on their surface. Additionally, testing can determine whether the cytoplasm of the cancer cells contain tartrate-resistant acid phosphatase (TRAP), a protein component that binds iron, as the presence of TRAP can differentiate hairy cell leukemia from other similar cancers. Examination of the bone marrow under a microscope will show whether any cells have the characteristic “fried egg” appearance of leukemia cells. Finally, additional tests may assess for the presence of a BRAF mutation. 

Less often, imaging studies may be performed to determine case severity. An ultrasound, a device that utilizes sound waves to create an image, can be used to see whether the spleen or liver are enlarged. The lymph nodes, spleen, and liver may also be observed via computerized tomography (CT) scans. 

How is hairy cell leukemia treated?

Hairy cell leukemia is usually addressed through careful monitoring of symptoms and chemotherapy. 

If a person is experiencing minor symptoms, and their blood counts are not significantly altered, the individual may need only regular monitoring appointments. Treatment of hairy cell leukemia may be postponed until the individual demonstrates any associated signs or symptoms.

When initiating treatment, chemotherapy is often the first line. Currently, pentostatin and cladribine are the chemotherapy drugs most commonly prescribed for hairy cell leukemia. About 70-95% of individuals taking one of these drugs experience complete remission, which is when no signs or symptoms of the cancer remain. Chemotherapy may cause several side effects, most often fever, nausea, and a weakened immune system, which increases risk of infection.

Repeated blood work, ultrasounds, or CT scans may be performed throughout treatment to monitor progress of treatment.

If the cancer does not respond to treatment, it is then referred to as a refractory or resistant cancer. Recently, moxetumomab pasudotox was approved for treating refractory hairy cell leukemia. In clinical trials, about 31% of individuals experienced a disappearance of cancer for at least 6 months. Though promising, this drug can also cause serious side effects, including capillary leak, when the clear fluid in the blood spreads out into cavities and muscles and causes a rapid drop in blood pressure, and hemolytic-urimic syndrome, a condition in which blood vessel damage in the kidneys leads to kidney failure

Splenectomy, surgical removal of the spleen, was a traditional method to treat hairy cell leukemia, but now it is typically conducted only if problems continue after chemotherapy. Undergoing a splenectomy may increase the length of remission.

About 8 years after treatment is completed, individuals often experience a relapse, or recurrence, of the cancer. At this time, pentostatin or cladribine may be administered again. Treatment may also feature monoclonal antibodies, laboratory-made proteins that target specific cells. For example, rituximab is a monoclonal antibody that targets the CD20 antigen, and vemurafenib is a monoclonal antibody that targets the BRAF protein. 

What is the survival rate for hairy cell leukemia?

Nearly 95% of people with hairy cell leukemia will live more than 10 years after diagnosis. Nonetheless, survival may vary based upon the individual’s response to treatment.

What are the most important facts to know about hairy cell leukemia?

Hairy cell leukemia is a blood cell cancer characterized by proliferation of cancerous lymphocytes, a type of white blood cell that fights infections when not cancerous. It is a rare disease, with only about 600-800 new cases a year in the United States. Hairy cell leukemia is most likely caused by a genetic mutation in the BRAF gene in stem cells in the bone marrow. Common symptoms include extreme tiredness, frequent infections, general weakness, and unexplained weight loss. Hairy cell leukemia is typically diagnosed based on the results of a medical examination, blood tests, and a bone marrow aspiration or biopsy. For individuals with no symptoms or mild ones, treatment may not be necessary until symptoms worsen. When treatment begins, it often starts with chemotherapy, involving drugs such as pentostatin or cladribine. If the cancer does not respond to initial chemotherapy, moxetumomab pasudotox may be prescribed. After years of remission, there is often a recurrence of the cancer. This may require renewed chemotherapy treatment or initiation of treatment with targeted monoclonal antibodies. The survival rate for hairy cell leukemia is high, with almost 95% of people surviving 10 years after diagnosis.

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Related links

Leukemia: Clinical Practice
Leukemia: Pathology review
Chronic leukemia

Resources for research and reference

Damon, L. E., & Andreadis, C. (2021). Hairy cell leukemia. In M. Papadakis, S. McPhee, & M. Rabow (Eds.), Current medical diagnosis & treatment 2021. McGraw-Hill. 

Jain, P., Pemmaraju, N., & Ravandi, F. (2014). Update on the biology and treatment options for hairy cell leukemia. Current Treatment Options in Oncology, 15(2), 187-209. DOI: 10.1007/s11864-014-0285-5

Leukemia & Lymphoma Society, & O’Brien, S. (2013). Hairy cell leukemia facts. Retrieved from https://www.lls.org/sites/default/files/file_assets/hairycellleukemia.pdf 

National Organization for Rare Disorders (NORD), & Munoz, J. (2013). Hairy cell leukemia. In Rare disease database. Retrieved from https://rarediseases.org/rare-diseases/hairy-cell-leukemia/

Tefferi, A., & Longo, D. L. (2018). Less common hematologic malignancies. In J. L. Jameson, A. Fauci, D. Kasper, S. Hauser, D. Longo, & J. Loscalzo (Eds.), Harrison's principles of internal medicine (20th ed.). McGraw-Hill.