ABSTRACT
Hairy cell leukemia (HCL) is an uncommon chronic B-cell lymphoproliferative disorder that has become one of the most effectively treated hematological malignancies. Remark able progress has been made in the treatment of patients with this disease since the clinical development of the purine analogs 2'-deoxycoformycin (2'-DCF) and 2-chlorodeoxyadenosine (2-CdA). These agents either inhibit or resist the action of the enzyme adenosine deaminase (ADA), which mediates the degradation of deoxyadenosine. Lymphocytes are abundant in deoxyadenosine, and the accumulation of deoxyadenosine is toxic to lympho cytes and results in lymphopenia, analogous to the lack of lymphocyte development in ADA-deficient children with severe combined immunodeficiency syndrome. Remarkably, equally high rates of durable complete remission (CR) are achieved in both untreated and previously treated patients, a phenomenon not typically observed in the treatment of malignant disease with cytotoxic chemotherapy. Furthermore, patients with large tumor burdens, identified by marked infiltration of the bone marrow and massive splenomegaly, have as favorable an outcome as those with minimal disease. Therefore, these agents are now the treatments of choice for all patients with HCL and have supplanted earlier ap proaches such as splenectomy and interferon-a. Because a single 7-day cycle of 2-CdA
induces a high rate of durable CR and is associated with few toxicities other than culturenegative fever, this agent is particularly attractive. However, it is not known if one purine analog offers a survival advantage over the other. Long-term follow-up will be necessary to identify such an advantage given the indolent natural history of the disease.
