Hairy Cell Leukemia

Abstract

Hairy cell leukemia is a B cell malignancy, accounting for 2% of all leukemias. Patients typically have splenomegaly, pancytopenia and an indolent course. Diagnosis requires identification of malignant cells in the bone marrow and peripheral blood with cytoplasmic projections and characteristic surface antigens. Splenectomy and interferon α were early treatments which have palliative value in the salvage setting. The purine analogs pentostatin and cladribine were found over 10 years ago to induce durable complete remissions in a high percentage of patients. Both are generally well tolerated, although with significant toxicity to CD4+ T cells and possibly hematopoietic stem cells, and it is unknown whether they differ in terms of long-term efficacy, safety, or association with secondary malignancies. Cladribine can induce complete remission with one cycle and is most commonly used. However, patients in complete remission can have minimal residual disease (assessed by immunologic studies) and its presence can increase the risk of early relapse. Molecular studies show that cladribine cannot eradicate the malignant hairy cell clone, and the lack of plateau in the disease free survival curve over time suggests that the present therapy cannot cure the disease. While retreatment with purine analogs is often successful, at least 25 to 35% of patients with HCL either initially or eventually become unresponsive and can succumb to infections and bleeding. The characteristic bright expression of several B-cell antigens on malignant cells, including CD20, CD22 and CD25, has led to the development of targeted therapy which is showing promising results in early clinical studies. Rituximab has activity, although duration and rates of response in clinical trials remain unclear. Recombinant immunotoxins LMB-2 and BL22 targeting CD25 and CD22, respectively, with truncated Pseudomonas exotoxin induce responses in 80 to 100% of patients who are resistant to purine analogs, and BL22 has a >60% complete remission rate in this setting. Further work is proceeding to increase the options for patients with hairy cell leukemia and to determine whether this disease can be cured.