Treatment protocols for hairy cell leukemia (HCL) are provided below, including those for initial treatment, resistant disease, variant HCL, and relapsed/refractory HCL. [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11]
Symptoms requiring initiation of treatment
Many patients with HCL appear to be asymptomatic even after diagnosis. Treatment should be initiated if the patient develops 1 or more of the following symptoms:
Abdominal fullness or discomfort due to splenomegaly
Complaints of fatigue, weakness, and weight loss
Bruising and bleeding secondary to severe thrombocytopenia, or with recurrent infections, which may be life-threatening, secondary to granulocytopenia and monocytopenia (absolute neutrophil count < 1000/µL with repeated infections [see the Absolute Neutrophil Count calculator], symptomatic anemia with a hemoglobin concentration < 11.0 g/dL, or bleeding due to a platelet count < 100,000/µL)
Patients may also rarely present with vasculitis
Initial treatment recommendations
Purine analogues cladribine and pentostatin are first-line agents in the treatment of HCL. Cladribine is more commonly used because of ease of administration. 
Cladribine 0.1 mg/kg/day by continuous IV infusion for 7d (FDA approved) or 0.14 mg/kg/day IV or SC over 2h for 5d (different schedules but no apparent difference in toxicity; can use growth factors if febrile neutropenia) or
Pentostatin 4 mg/m 2 IV bolus or over 30min every 2wk with 1.5 L of hydration for each dose for 3-6mo or
Interferon alfa 2b 2 million U/m 2 SC 3 times per week for 12-18mo for relapsed or refractory HCL
Splenectomy (laparoscopic preferred) is considered for patients with bleeding from severe thrombocytopenia or failure to respond to systemic therapy; administer pneumococcal, meningococcal, and Haemophilus influenzae vaccines prior to surgery
For patients who obtain no benefits from the use of a purine analogue, the use of an alternative analogue is recommended. In addition, the use of interferon alfa or a splenectomy may be an option.
Variant hairy cell leukemia
Variant hairy cell patients are resistant to the standard treatments, which include the use of purine analogues and interferon alfa. These patients may be candidates for treatment with available monoclonal antibodies.
Patients may relapse after initial treatment, so it is important to retreat them with a second cycle of treatment that can lead to remission.
Although pentostatin and cladribine provide responses in greater than 85% of patients, and a median progression-free survival of up to 15y, alternative treatments, such as the addition of rituximab, are needed for patients who become refractory to these treatments.