Hairy-cell leukemia (HCL) is an infrequent B-cell malignancy usually associated with pancytopenia and splenomegaly. About 600 cases are reported yearly in the United States. Despite its relative rarity, there are a disproportionate number of highly effective therapies available.
The male-to-female ratio of HCL is 4:1. The median age at presentation is 50 years. The etiology is unknown.
HCL can be confused with malignant lymphomas, splenic lymphoma with villous lymphocytes (SLVLs), CLL, other non-Hodgkin lymphomas in leukemic phase, and occasionally even myelodysplastic syndromes.
The indications for treatment of HCL are an absolute neutrophil count (ANC)
< 1,000/μL, a platelet count < 100 β 103/μL, or a hemoglobin level < 10 g/dL; leukemic phase of HCL; symptomatic splenomegaly; recurrent infections; or autoimmune complications.
The criteria for a CR are normalization of the complete blood cell (CBC) count, with an ANC > 1,500/μL, a platelet count > 100,000/μL, and a hemoglobin level > 12 g/dL; regression of organomegaly to normal; and bone marrow and peripheral blood free of hairy cells. PRs require reduction of the hairy cells in the bone marrow to < 50%, < 5% hairy cells in peripheral blood, > 50% reduction in organomegaly, and normalization of the CBC count.
This procedure is reserved for patients with splenic rupture, infarcts, a massively enlarged spleen, severe hypersplenism, or failure to respond to systemic chemotherapy.
Interferon-alfa, at a dose of 3 mU/daily administered by IM or SC injection for 6 months followed by 3 mU/daily three times weekly for 12 or 24 months, induces a CR in 8% to 10% of patients and a PR in 74%. The median time to response was 6 months in patients achieving a PR and 14 months in those achieving a CR. Patients frequently relapse between 12 and 24 months after discontinuation of therapy. The superiority of purine analog therapy has essentially led most clinicians to abandon the use of interferon for this disease.
The recommended dose of pentostatin is 4 mg/m2 by IV bolus every other week until a CR is obtained. Usually, patients require a median of 8 courses (range, 4–15). The CR rate varies between 59% and 89% in different studies, and the PR rate varies between 4% and 37%. Responses can last for many years, and patients who relapse often respond to retreatment with pentostatin. In an update of a large randomized trial comparing pentostatin and interferon-alfa, Flinn et al reported that in 241 patients with HCL treated with pentostatin, the 10-year overall survival rate was 81%, with only two deaths (1%) attributable to HCL.
Cladribine(Drug information on cladribine) shows activity in treating HCL similar to that of pentostatin. Due to this finding and the fact that cladribine is given as 1 cycle of a 7-day continuous infusion or a 5-day bolus, this agent usually is the preferred treatment of this disorder. Piro et al treated 144 HCL patients with cladribine, 0.1 mg/kg/daily by continuous IV infusion for 7 days. A total response rate of 97% was obtained, with 85% CRs and 12% PRs. Response was independent of previous treatment with interferon or splenectomy, and three patients whose disease was refractory to pentostatin responded to cladribine. Recovery of CBC counts occurred on average by day 61 (range, 11–268 days).
The largest series reporting long-term follow-up results for patients with HCL treated with cladribine was from the Scripps group. A total of 349 patients, with a median duration of response follow-up of 59 months, were evaluated. Twenty-six percent had relapsed at a median of 29 months, but most of them were patients who had achieved only a PR. The time-to-treatment failure rate at 48 months was only 16% in complete responders.
Else et al reported on a large series of 219 patients with HCL, comparing their experience with pentostatin and cladribine. Treatment results were similar in terms of frequency of CR, relapse, and overall survival. Though the results are excellent, with more than 95% of patients alive at 10 years, the disease-free survival curves do not plateau, indicating these drugs are not curative in HCL. Recently, a phase II study evaluated the combination of cladribine followed by rituximab(Drug information on rituximab) in patients with hairy cell leukemia. This combination was well tolerated and effective, with 100% of patients achieving a CR.
The NCI evaluated a recombinant immunotoxin containing an anti-CD22 variable domain fused to a truncated Pseudomonas exotoxin; it was given by IV infusion every other day for a total of three doses. Sixteen patients whose disease was resistant to cladribine were treated; 2 achieved a PR and 11 achieved a CR. Of the 11 patients, 3 who had a CR relapsed and were retreated; all of these patients achieved a second CR.