The role of interferon in the treatment of hairy cell leukemia.

Hairy cell leukemia (HCL) is a rare chronic lymphoproliferative disorder usually manifested by pancytopenia. Prior to the use of interferon in the treatment of this disease, initial therapy most often consisted of splenectomy. Patients with progressive disease after splenectomy often benefited from low-dose chlorambucil, although many other treatment modalities had been tested. Interferon (partially purified) was first reported to be effective in HCL by Quesada et al in 1984, with responses in seven of seven patients. Subsequent studies demonstrated that recombinant interferon was also effective. Major responses (normalization of peripheral blood counts) have been obtained in 50% to 80% of patients treated to date, and virtually all patients show some improvement. There is rapid improvement in the platelet count (1 to 2 months), followed by improvement in absolute neutrophil count (2 to 3 months) and hemoglobin (3 to 6 months). In addition, leukemic patients have a rapid reduction in circulating hairy cells. Interferon alpha also has been demonstrated to reduce the incidence of serious infections and the need for transfusions, as compared to the 6-month period prior to therapy. Bone marrow shows improvement as well, with a reduction in hairy cells and an increase in normal precursors. However, bone marrow remains abnormal, with increased reticulin, decreased myeloid precursors, and, usually, discernible hairy cells. Following discontinuation of therapy, a slow increase in hairy cells may occur. The mechanism of interferon's action is unknown. Interferon induces the synthesis of new proteins and the formation of new organelles. Although natural killer cell activity increases with the introduction of interferon, these changes probably do not mediate the response to the agent. Interferon has been demonstrated in vivo to have a direct antiproliferative effect on hairy cells. We conclude that interferon is highly effective in progressive disease following splenectomy. Its exact role in nonsplenectomized patients remains to be determined, as does its optimal use in the long-term management of HCL.