Hairy Cell Leukemia (HCL)

What hairy cell leukemia is

HCL develops when a mature B lymphocyte acquires gene changes, most often the BRAF V600E mutation (found in almost all classic HCL), and begins dividing uncontrollably. The abnormal cells collect in:

• the bone marrow, crowding out normal blood production and causing fibrosis
• the spleen, which enlarges (splenomegaly)
• the liver and, less often, lymph nodes
• the blood, usually in small numbers

A related but different disease, HCL variant (now classified separately), lacks the BRAF mutation and is harder to treat.

Symptoms

Many people are diagnosed after routine blood tests show low counts. When symptoms occur, they come from low blood counts and the enlarged spleen:

• tiredness, weakness and shortness of breath from anemia
• frequent or unusual infections from low neutrophils (neutropenia) and monocytes
• easy bruising, nosebleeds and bleeding gums from low platelets
• feeling full quickly, or discomfort in the upper left abdomen from an enlarged spleen
• weight loss, night sweats or fever in some people

Diagnosis

• complete blood count: low red cells, white cells and platelets (pancytopenia); low monocytes are characteristic
• blood smear: may show hairy cells
• flow cytometry: identifies HCL by surface markers (CD11c, CD25, CD103, CD123)
• bone marrow biopsy: shows infiltration and fibrosis; marrow is often hard to aspirate ("dry tap")
• BRAF V600E testing: confirms classic HCL and identifies a target for treatment
• imaging: ultrasound or CT to measure the spleen and liver

Treatment

Not everyone needs treatment straight away. People with mild, stable counts and no symptoms may be monitored.

When to treat

Treatment is started for symptoms, an enlarged spleen causing problems, recurrent infections, or significantly low blood counts.

First-line treatment

• purine analogs: cladribine (usually a single short course) or pentostatin (repeated infusions over months). These induce complete remission in most patients, often lasting many years.
• rituximab (an antibody against CD20) is often added to improve the depth and length of remission.

Relapsed or refractory disease

• repeat purine analog, with or without rituximab
• BRAF inhibitors (vemurafenib or dabrafenib, sometimes combined with rituximab or the MEK inhibitor trametinib) target the BRAF mutation
• moxetumomab (an immunotoxin) has been used but is no longer widely available
• ibrutinib, a BTK inhibitor, for some patients
• splenectomy is now rarely needed

Supportive care

• infection prevention, since counts and immunity are low during and after treatment
• vaccines (avoid live vaccines during treatment)
• transfusions if needed

Outlook

HCL is one of the most treatable leukemias. Most people achieve remission with the first treatment, and many remain in remission for 10 years or more. When it returns, it usually responds to further treatment. Life expectancy for many patients is close to that of people without HCL. Lifelong follow-up with blood counts is recommended.

HCL is a type of chronic leukemia, but it behaves very differently from chronic myeloid leukemia, which arises from myeloid cells and is treated with tyrosine kinase inhibitors.

Frequently asked questions

What are the symptoms of hairy cell leukemia?

Common symptoms are tiredness, weakness, frequent infections, easy bruising or bleeding, and fullness or discomfort in the upper left abdomen from an enlarged spleen. Some people have no symptoms and are diagnosed from routine blood tests.

Is hairy cell leukemia curable?

It is not usually considered curable, but it is highly treatable. Most people go into long-lasting remission after treatment with cladribine or pentostatin, often with rituximab, and relapses usually respond to further treatment. Many people live a normal lifespan.

What is the life expectancy with hairy cell leukemia?

For most people treated with modern therapy, life expectancy is close to normal. Long remissions of 10 years or more are common. Outcomes are less favorable for HCL variant, which is a different disease.

Why is it called hairy cell leukemia?

Under a microscope, the leukemia cells have thin, hair-like projections from their surface. This distinctive appearance gave the disease its name and helps pathologists recognize it.

How is hairy cell leukemia treated?

Most patients receive a purine analog, either a short course of cladribine or repeated pentostatin infusions, often combined with rituximab. Targeted drugs that block the BRAF mutation are used if the disease returns. Some people with mild disease are monitored first.