Hairy cell leukemia (HCL)

Hairy cell leukemia (HCL) is often first suspected from a complete blood count, a routine test of red cells, white cells and platelets. In HCL, all three are often low. A low number of monocytes, one kind of white blood cell, is a useful clue. A specialist then looks at the blood under a microscope for cells with hair-like edges.

The key test is flow cytometry, which reads the markers on the surface of cells. Hairy cells carry a typical set, including CD11c, CD25, CD103 and CD123. This test can usually make the diagnosis. International expert guidelines also advise a sensitive test for the BRAF V600E gene change in everyone with HCL. This change is almost never found in look-alike diseases, so the test helps tell them apart.

A bone marrow aspiration and biopsy shows how much of the marrow the leukemia has filled. The marrow is often scarred (fibrosis). Then the needle may not be able to draw out a liquid sample, which is called a “dry tap.” Special stains on the biopsy help confirm HCL. A CT scan of the belly may be done to check for a swollen spleen or lymph nodes.

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 An earlier medicine for relapsed HCL, moxetumomab, has been withdrawn from the US market.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.

For most people, HCL is a long-term illness that can be kept under control for many years. In a large Italian study, about 2 in 3 people had a complete remission after their first cladribine treatment. A complete remission means no signs of the leukemia on standard tests. Other studies report rates from about half to 9 in 10. Many remissions last for years.

A few things shape the outlook. One is how deep the first response is: in the Italian study, complete remissions lasted much longer than partial ones. Another is how HCL responds if it comes back. Treating it again often brings another remission. The exact diagnosis matters too. Classic HCL with the BRAF V600E change responds well to the usual medicines. The look-alike disease called HCL variant tends to have shorter-lasting responses.

In the Italian study, very few people died from HCL itself: 2 of 513. Infections, heart disease and other illnesses were more common causes of death. Expert guidelines stress preventing infections and keeping up with routine checkups, such as cancer screening. These numbers describe groups of people, not what will happen to any one person.