Hairy Cell Leukemia · What Is It, How Common Is It, and More

While the exact mechanisms underlying hairy cell leukemia are not fully understood, a BRAF gene mutation is likely to be its most common cause.  BRAF provides instructions to make the BRAF protein, which is involved in cell replication. The mutation causes the BRAF protein to remain 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 BRAF gene mutation occurs in hematopoietic stem cells, or the blood stem cells found in the bone marrow. These cells are able to differentiate into white blood cells, red blood cells, and platelets. In hairy cell leukemia, mutated hematopoietic stem cells overproduce B lymphocytes, decreasing the space available in the bone marrow for other types of blood cells. Additionally, cancerous cells may release substances that prevent stem cell differentiation into other blood cell types. 

Possible risk factors for the development of hairy cell leukemia include exposure to pesticides, farming, and ionizing radiation. Regardless, this cancer most commonly affects adults with a median age of 58, 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. 

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 result from reduced levels in all types of blood cells (i.e., pancytopenia). Decreased production of red blood cells (i.e., anemia) can cause extreme tiredness, general weakness, and shortness of breath. A reduction in neutrophils (i.e., neutropenia) and monocytes (i.e., monocytopenia), which are two types of white blood cells, can weaken the body's immune response and result in frequent infections and fevers. Individuals with hairy cell leukemia are thus more susceptible to uncommon infections, such as those caused by mycobacteria, which is a group of bacteria including the one responsible for tuberculosis. Additionally, low numbers of platelets (i.e., thrombocytopenia), critical to blood clotting, may make the individual more susceptible to bruising or bleeding. 

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

Diagnosis of hairy cell leukemia is based on a clinical evaluation including a review of the individual's signs and symptoms, medical history, physical examination, and laboratory findings. If hairy cell leukemia is suspected, a complete blood count (CBC) is typically performed to determine the proportions of each blood cell type and to identify pancytopenia, if present. Other blood tests may include a peripheral blood smear, in which the blood is microscopically examined to look for hairy cells, and blood chemistry studies (e.g., liver and kidney function tests). 

If initial blood tests suggest hairy cell leukemia, additional diagnostic tests may be performed to confirm the diagnosis. A bone marrow aspiration is usually performed by inserting a large needle into the upper part of the hip bone to withdraw a small sample of the fluid portion of the bone marrow. In hairy cell leukemia, a “dry tap”, meaning no bone marrow is obtained during aspiration, is common. When a dry tap occurs, a bone marrow biopsy is conducted, in which the needle removes a cylinder-shaped sample of solid bone containing bone marrow. 

Hairy cell leukemia is usually treated with careful symptoms monitoring and chemotherapy.  

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

When initiating treatment, chemotherapy is the first line. Currently, the most commonly prescribed chemotherapy drugs are pentostatin or cladribine. About 70-90% of individuals taking one of these drugs experience complete remission, meaning resolution of all signs and symptoms. Chemotherapy drugs may be associated with rituximab, a monoclonal antibody – laboratory-made proteins targeting specific antigens - targeting the CD20 antigen on B  lymphocytes. This combination has been shown to improve remission.  

Splenectomy, the surgical removal of the spleen, was a standard method to treat hairy cell leukemia. Today, it is typically conducted only when other therapies have failed or if splenomegaly is significantly symptomatic; but because chemotherapy already reduces the size of the spleen, it is rarely performed.  

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

In case of recurrence, re-treatment with pentostatin or cladribine, possibly with rituximab, is recommended. Other experimental approaches include the use of monoclonal antibodies targeting mutated proteins, such as BRAF inhibitors (e.g., vemurafenib) and MEK inhibitors (e.g., trametinib). These are among the drugs undergoing investigations in clinical trials.