Hairy cell leukemia

Hairy cell leukemia is a mature B cell neoplasm. It is usually classified as a sub-type of chronic lymphoid leukemia for convenience. It is uncommon, representing about 2% of all leukemias, or less than a total of 2000 new cases diagnosed each year in the North America and Western Europe combined.

 Originally known as histiocytic leukemia, malignant reticulosis, or lymphoid myelofibrosis in publications dating back to the 1920s, this disease was formally named leukemic reticuloendotheliosis and its characterization significantly advanced by Bertha Bouroncle, M.D., and her colleagues at the Ohio State University College of Medicine in 1958. Its common name, which was coined in 1966, is derived from the appearance of the cells under a microscope.

 Two variants have been described: Hairy cell leukemia-variant, which usually is diagnosed in older men (median age above 70), and a Japanese variant. The non-Japanese variant is more difficult to treat than either 'classic' HCL or the Japanese variant HCL.

 Risk Factors and Causes

 Most patients are white males over the age of 50, although it has been diagnosed in at least one teenager. Men are four to five times more likely to develop hairy cell leukemia than women. It does not appear to be hereditary, although occasional familial cases have been reported, usually showing a common HLA type.

 The cause is unknown, but generally believed not to be caused by tobacco, ionizing radiation, pesticides, or industrial chemicals other than possibly diesel. Farming and gardening appear to increase the risk in some studies. The possibility that HCL is caused by a random accident during routine cell division can not be ruled out.

Symptoms

 In hairy cell leukemia, the broken "hairy cells" build up in the bone marrow, which means that the bone marrow has difficulty producing enough normal cells: white blood cells to fight infections, red blood cells to carry oxygen, and platelets to stop bleeding. Consequently, patients usually present with infection, anemia-related fatigue, and/or easy bleeding.

 Most symptoms are often vague, such as "persistent fatigue" or "not feeling well." Some of the leukemic cells may gather in the spleen and cause it to swell; this can have the side effect of making the person feel full even when they haven't eaten much.

 Hairy cell leukemia is commonly diagnosed after a routine blood count shows unexpectedly low numbers for one or more kinds of blood cells, or after unexplained bruises or unexplained infections, such as repeated bouts of pneumonia in an otherwise apparently healthy patient. 

Platelet function may be somewhat impaired in HCL patients, although this does not appear to have any significant practical effect. It may result in somewhat more mild bruises than would otherwise be expected for a given platelet count or a mildly increased bleeding time for a minor cut. It is likely the result of producing slightly abnormal platelets in the overstressed bone marrow tissue. 

Patients with a high tumor burden may also have somewhat reduced levels of cholesterol, especially in patients with an enlarged spleen. Cholesterol levels return to more normal values with successful treatment of HCL.

Diagnosis

 The diagnostic path may have begun with a simple test like a complete blood count, but this is not adequate to diagnose HCL. Most patients require a bone marrow biopsy for proper diagnosis. The bone marrow biopsy is used to confirm the presence of HCL and also the absence of any secondary disease. Abnormal white blood cells bearing hair-like projections from the cytoplasm are seen on blood film examination or bone marrow biopsy. The diagnosis can be confirmed by viewing the cells with a special stain, known as TRAP, or tartrate resistant acid phosphatase.

 It is also possible to definitively diagnose hairy cell leukemia through a flow cytometry blood test which identifies characteristic proteins on the cell surfaces. These cancerous cells are larger than normal and positive for CD19, CD20, CD22, CD11c, CD25, CD103, and FMC7. Hairy cell leukemia-variant (HCL-V), which shares some characteristics with B cell prolymphocytic leukemia (B-PLL), does not show CD25 (also called the Interleukin-2 receptor, alpha). As this is relatively new and expensive technology, its adoption by physicians is not uniform, despite the advantages of comfort, simplicity, and safety for the patient when compared to a bone marrow biopsy.

 Because a patient could have more than one similar disease, it is also necessary to rule out the presence of leukemias and lymphomas such as SMZL or B-PLL. The presence of these diseases is easily checked during a flow cytometry test, where they characteristically show different results. Careful review of bone marrow biopsy samples is also reliable for this purpose.

 On physical exam, patients may display massive splenomegaly. This is less likely among patients who are diagnosed through routine blood work, when the disease is at an early stage.

 Treatment

Several treatments are available, and successful control of the disease is common.

 Not everyone needs treatment. Treatment is usually given when the symptoms of the disease interfere with the patient's everyday life, or when white blood cell or platelet counts decline to dangerously low levels, such as an absolute neutrophil count below one thousand cells per microliter (1.0 K/uL). Not all patients need treatment immediately upon diagnosis, and about 10% of patients will never need treatment.

 Treatment delays are less important than in solid tumors. Unlike most cancers, treatment success does not depend on treating the disease at an early stage. Because delays do not affect treatment success, there are no standards for how quickly a patient should receive treatment. However, waiting too long can cause its own problems, such as an infection that might have been avoided by proper treatment to restore immune system function. Also, having a higher number of hairy cells at the time of treatment can make certain side effects somewhat worse, as some side effects are primarily caused by the body's natural response to the dying hairy cells. This can result in the hospitalization of a patient whose treatment would otherwise be carried out entirely at his hematologist's office.

 Single-drug treatment is normal. Unlike most cancers, only one drug is normally given to a patient at a time. While monotherapy is normal, combination therapy -- typically using one first-line therapy and one second-line therapy -- is being studied in current clinical trials and is increasingly used for refractory cases. It is unclear whether combining rituximab with