Hairy cell leukemia (HCL)

Hairy cell leukemia is a cancer of B cells, the white blood cells that normally make antibodies to fight germs. The abnormal B cells build up in the bone marrow, the soft tissue inside bones where blood is made, and in the spleen. Under a microscope they have thin, hair-like threads on their surface, which is how the disease got its name.

It is rare. In the United States there are only about 1,200 to 1,300 new cases a year, and it makes up about 2 in every 100 leukemias. Unlike the acute leukemias, it usually grows slowly.

A related disease once called “hairy cell leukemia variant” is now classed separately by the World Health Organization, as splenic B-cell lymphoma/leukemia with prominent nucleoli. It behaves differently and responds less well to the usual HCL medicines, so getting the exact diagnosis matters.

HCL starts when a B cell picks up gene changes during a person’s life. Nearly everyone with classic HCL has a change called BRAF V600E in the leukemia cells. It works like a switch stuck in the “on” position, telling the cells to keep growing and surviving. Testing for it helps confirm the diagnosis and points to medicines that block this signal.

The change is found only in the leukemia cells. It is not inherited from a parent, and HCL is not contagious. HCL is more common in men than in women and is usually found in middle age or later. Why it starts in a particular person is usually unknown.

As hairy cells crowd the marrow, it makes fewer normal blood cells. Low red cells (anemia) cause tiredness and shortness of breath. Low platelets can lead to easy bruising or bleeding. Monocytes and other infection-fighting white cells are often very low, so infections can be frequent or serious.

The spleen often swells, which can cause pain or fullness below the ribs on the left side. Swollen lymph nodes are less common when HCL is first found. Some people have no symptoms at all when it is diagnosed.

Diagnosis uses a blood count, a close look at the blood cells, and flow cytometry, a test that reads the markers on the surface of cells. A bone marrow biopsy is often done too, along with a test for the BRAF change.

Not everyone needs treatment right away. If blood counts stay at an acceptable level and there are no symptoms, the care team may watch closely with regular checkups. Treatment usually starts when counts fall too low, the spleen grows or causes symptoms, or infections become a problem.

The usual first treatment is a chemotherapy medicine called a purine analog: cladribine or pentostatin. Adding rituximab, an antibody medicine that targets B cells, is increasingly common because it can deepen the response. In studies, most people respond, and complete remissions are common. Purine analogs weaken the immune system for a long time, so for some people, such as older or frail adults at higher risk of infection or anyone with an active infection, doctors may choose a non-chemotherapy option first, such as vemurafenib with rituximab. Vemurafenib is widely used for HCL, although in the US it is not approved for this disease.

HCL often comes back, sometimes many years later. Options then include another purine analog with rituximab, or targeted medicines. Vemurafenib, or dabrafenib with trametinib, block the BRAF signal; ibrutinib, a BTK inhibitor, blocks a different growth signal inside B cells. An earlier medicine for relapsed HCL, moxetumomab, has been withdrawn from the US market.

A donor (allogeneic) stem cell transplant is very rarely used. The 2025 European transplant recommendations do not list HCL among the conditions they rate. The largest study of its kind, published in 2023 from a European registry, found 24 adults who had a first donor transplant for HCL at 19 centers between 1996 and 2018; the typical patient had already been through six earlier treatments. The authors urged the “utmost caution” in choosing it, and expect newer medicines to make it needed even less often.

Many people spend long stretches without treatment, with regular blood tests in between. Because HCL returns in many people, follow-up continues for years. Studies of people with classic HCL have found that many live for decades after diagnosis, although that is an average across groups and cannot predict one person’s course.

Purine analogs lower blood counts and immune defenses for a time. During and after treatment, preventing infections and treating a fever quickly matter a great deal. The care team can explain which symptoms need an urgent call.

A rare cancer can feel isolating. Patient groups for HCL share information about treatment and about specialist centers that see many cases, and they connect people with others who have been through it.

Most people with HCL will never need a donor. The usual treatments are medicines, and transplant is not part of standard HCL care.

A donor transplant has been used only rarely, for people whose HCL kept coming back or stopped responding to many treatments. In the European study of 24 such adults, about half received cells from an unrelated volunteer donor, and most of the rest from a brother, sister or other relative.

So joining a registry is not the usual next step for someone with HCL. Registries serve patients with many blood cancers and blood disorders, and a well-matched volunteer can make a transplant possible for someone who has no matched relative.