Approximately 90 percent of patients require treatment at time of diagnosis. Indications include:
— Symptomatic splenomegaly or lymphadenopathy.
— Anemia (Hb level less than 10 g/dL).
— Thrombocytopenia (platelet count <100 × 109/L).
— Granulocytopenia (neutrophil count < 1.0 × 109/L) with recurrent bacterial or opportunistic infections.
— Leukemic phase (white cell count > 20 × 109/L).
— Painful bony involvement.
Cladrabine (2-Chlorodeoxyadenosine) is the treatment of choice for hairy cell leukemia.
— A purine analogue given as a 7-day continuous intravenous infusion at 0.1 mg/kg per day. (Successful subcutaneous, oral, and weekly dosing has been reported.)
— Can induce long-lasting complete responses in greater than 75 percent of patients. Initially, 91 percent have complete response and 7 percent a partial response.
— Sixteen percent of complete responders have evidence of relapse at 48 months. Approximately 90 percent of patients initially treated with cladrabine who relapse will have a complete (62%) or partial response (26%) when retreated with the same drug.
— In a subsequent study of 207 patients monitored for at least 7 years after cladrabine treatment, 95 percent had achieved a complete response and 5 percent a partial response after a single 7-day course. The overall survival at 108 months was 97 percent and the median disease-free duration for all responders was 98 months.
— Notable toxicities of cladrabine:
— A purine analogue that inhibits adenosine deaminase.
— A good second choice drug for patients unresponsive or refractory to cladrabine.
— Administered as an intravenous bolus of 4 mg/m2 every other week for 3 to 6 months until maximum response as judged by decrease of blood and marrow hairy cells, reduced spleen size, and improvement in normal blood cell counts.
— Complete response rates with pentostatin (~50%) are lower than that achieved with cladribine.
— Pentostatin may not be effective in patients refractory to cladribine.
— Notable toxicities:
Fever, rash, conjunctivitis.
Reversible renal dysfunction.
Mild hepatic toxicity.
Depletion of CD4+ cells.
— Complete response rate is 8 percent; 74 percent achieve a partial response.
— Not curative; 50 percent relapse less than 2 years after treatment.
— Usual dosage schedule is 2 × 106 U IFN-α2b/m2 subcutaneously three times weekly for 12 months or 3 × 106 U IFN-α2a/m2 subcutaneously daily for 6 months and decreased to 3 times per week for an additional 6 months.
— Not as effective as purine analogues.
— Hairy cells express CD20 and thus an anti-CD20 monoclonal antibody is rational.
— The responses have been modest but it should be considered in patient's refractory to cladrabine and pentostatin.
— 375 mg/m2 intravenously weekly for 4 to 8 weeks.
— A proportion (25 to 75%) of patients has a complete or partial remission, which may be sustained for several years in a proportion of responders. Others relapse and progress.
Anti-CD22 Immunotoxin BL22
— Anti-CD22 fused to a Pseudomonas exotoxin.
— Can induce remissions in a high proportion of patients who are refractory to cladrabine.
— Associated with a reversible hemolytic uremic syndrome in a minority of patients.
— Not curative.
— Current indications:
Massive, painful, and/or ruptured spleen.
Pancytopenia and an active infection with opportunistic pathogen (e.g., Mycobacterium). Splenectomy usually results in marked increase in neutrophil and monocyte count and better response to antimicrobial treatment.
Failure of systemic chemotherapy.
Granulocyte colony-stimulating factor (G-CSF):
— May ameliorate neutropenia.
— Adjunct to therapy in cases of infection.
— Lytic bone lesions can be treated with low-dose irradiation.