Current Clinical Practice: Treatment of Hairy Cell Leukemia at the Close of the 20th Century

Abstract

In the last half of this century, hairy cell leukemia was recognized as a distinct B-cell malignancy, accounting for 2% of all leukemias. Characteristics include splenomegaly, pancytopenia, a usually indolent course, and responsiveness to both interferon and purine analog therapy. Accurate diagnosis requires the demonstration of malignant cells in the bone marrow and peripheral blood which contain cytoplasmic projections and characteristic surface antigens. Splenectomy was identified early as a palliative therapy, and in 1984 systemic treatment with interferon alpha was first reported to induce complete remissions. Soon thereafter, the purine analog deoxycoformycin was found to induce more durable complete remissions in a higher percentage of patients. In 1990, 2-Chlorodeoxyadenosine, a new purine analog therapy, was reported to be capable of inducing long-term durable responses in most patients after a single cycle. Current challenges include identifying which purine analog is the least toxic since both appear similarly effective, and neither appear to add to the already increased rate of second malignancies occurring in these patients. Moreover, up to 25% of patients with hairy cell leukemia fail initially or eventually to respond to standard therapy, making the development of new approaches necessary. The characteristic bright expression of several B-cell antigens on the malignant cells, including CD20, CD22 and CD25, has led to the development of targeted biotherapeutic approaches. A recombinant immunotoxin targeting CD25 has recently been reported to induce major responses and it is likely that other successful targeted approaches will be reported early in the new century.

Keywords:

• Purine analog
• cladribine
• deoxycoformycin
• interferon
• monoclonal antibody
• recombinant immunotoxin
• second malignancy