The disease was formally named leukemic reticuloendotheliosis, and its characterization was significantly advanced by Bertha Bouroncle and colleagues at the Ohio State University College of Medicine in 1958.

Its common name, which was coined in 1966,[3] is derived from the "hairy" appearance of the cytoplasmic projections from malignant B cells under a microscope.

Exposure to tobacco smoke, ionizing radiation, or industrial chemicals (with the possible exception of diesel) does not appear to increase the risk of developing it.

[11] The U.S. Institute of Medicine (IOM) found a correlation which permits an association between exposure to herbicides and later development of chronic B-cell leukemias and lymphomas in general.

However, the IOM extrapolated data from chronic lymphocytic leukemia and non-Hodgkin lymphoma to conclude that HCL and other rare B-cell neoplasms may share this risk factor.

Bone-marrow failure is caused by the accumulation of hairy cells and reticulin fibrosis in the bone marrow, as well as by the detrimental effects of dysregulated cytokine production.

However, if large numbers of hairy cells are in the blood stream, then normal or even high lymphocyte counts may be found.

The bone marrow biopsy is used both to confirm the presence of HCL and also the absence of any additional diseases, such as Splenic marginal zone lymphoma or B-cell prolymphocytic leukemia.

[27] Pentostatin and cladribine administered as monotherapy (without concurrent rituximab) provide some benefit to many people with HCL-V, but typically induce shorter remission periods and lower response rates than when they are used in classic HCL.

[25] HCL-V, which usually features a high proportion of hairy cells without a functional p53 tumor suppressor gene, is somewhat more likely to transform into a higher-grade malignancy.

Purine analogs are very effective in the treatment of HCL, achieving remission rates of 80-90%; with remission being defined as normal or near normal blood counts, no palpable splenomegaly and no hairy cells on bone marrow biopsy or peripheral blood without immunostaining, or minimal hairy cells with immunostaining (known as measurable residual disease).

[2] Rituximab, the anti-CD20 monoclonal antibody, may be added to purine analogs during initial treatment and is associated with increasing the remission rate to nearly 100%.

[36] Relatively few patients have significant side effects other than fatigue and a high fever caused by the cancer cells dying, although complications such as infection and acute kidney failure have been seen.

[citation needed] During the weeks following treatment, the patients' immune systems are severely weakened, but their bone marrow will begin to produce normal blood cells again.

Rituximab may cause a serum sickness reaction which presents with fevers, joint pain and rash approximately 4-10 days after any infusion.

Common criteria for treatment success include: IFN-alpha is considered the drug of choice for pregnant women with active HCL.

[2] IFN-alpha works by sensitizing the hairy cells to the killing effect of the immune-system hormone TNF-alpha, whose production it promotes.

People with low neutrophil counts may be given filgrastim or a similar hormone to stimulate production of white blood cells.

[48] In this study, patients who received filgrastim were just as likely to experience a high fever and to be admitted to the hospital as those who did not, even though the drug elevated their white blood cell counts.

Hematopoietic stem cell transplantation for HCL does not improve relapse free survival at 5 years and is associated with a high mortality rate above 15% and is not recommended.

[49] A majority of new patients can expect a disease-free remission time span of about ten years, or sometimes much longer after taking one of these drugs just once.

As with B-cell chronic lymphocytic leukemia, mutations in the IGHV on hairy cells are associated with better responses to initial treatments and with prolonged survival.

After five years' clinical remission, patients in the United States with normal blood counts can often qualify for private life insurance with some US companies.

[51] Accurately measuring survival for patients with the variant form of the disease (HCL-V) is complicated by the relatively high median age (70 years old) at diagnosis.

While survivors of solid tumors are commonly declared to be permanently cured after two, three, or five years, people who have hairy cell leukemia are never considered 'cured'.

Of the original 358-patient cohort treated with cladribine at the Scripps Clinic, 9 of 19 in continuous CR for a median of 16 years were free of HCL — even sensitive testing for measurable or minimal residual disease (MRD)[52] found an absence of hairy cells.

Between regularly scheduled appointments, people who have hairy cell leukemia should report any health problems, especially viral or bacterial infections, as soon as they appear.

Aggressive surveillance and prevention efforts are generally warranted, although the lifetime odds of developing a second cancer after HCL diagnosis are still less than 50%.

[2] It does not appear to be hereditary, although rare familial cases that suggest a predisposition have been reported,[55] usually showing a common Human Leukocyte Antigen (HLA) type.

The major remaining research questions are identifying the cause of HCL and determining what prevents hairy cells from maturing normally.