LASTING REMISSIONS IN HAIRY-CELL LEUKEMIA INDUCED BY A SINGLE INFUSION OF 2-CHLORODEOXYADENOSINE

被引:485
|
作者
PIRO, LD
CARRERA, CJ
CARSON, DA
BEUTLER, E
机构
[1] Department of Molecular and Experimental Medicine, Research Institute of Scripps Clinic, Scripps Clinic and Research Foundation, La Jolla, Calif
来源
NEW ENGLAND JOURNAL OF MEDICINE | 1990年 / 322卷 / 16期
关键词
D O I
10.1056/NEJM199004193221605
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
2-Chlorodeoxyadenosine is a simple purine nucleoside that has previously been shown to be effective in the treatment of low-grade malignant disorders of lymphoid tissue, including chronic lymphocytic leukemia and non-Hodgkin's lymphoma. Because of these encouraging results, we treated 12 patients with another low-grade B-cell neoplasm, hairy-cell leukemia. The patients received 2-chlorodeoxyadenosine (0.1 mg per kilogram of body weight per day) by continuous infusion for seven days. All the patients responded to treatment. Eleven had complete remissions characterized by the normalization of peripheral blood and bone marrow and disappearance of tumor masses. The longest remission has been 3.8 years. None of the patients have relapsed, and the median duration of remission has been 15.5 months. No serious toxic reactions occurred as a result of 2-chlorodeoxyadenosine therapy. These results suggest that 2-chlorodeoxyadenosine may be the most effective therapy available for hairy-cell leukemia. The administration of 2-chlorodeoxyadenosine resulted in a higher rate of complete remission than is observed with interferon alfa, and it required no maintenance therapy. Its toxicity may be lower than that of deoxycoformycin, and the responses were achieved with single courses of treatment. FIRST described by Bouroncle et al. in 1958 as leukemic reticuloendotheliosis,1 hairy-cell leukemia is now recognized to be a low-grade B-cell neoplasm.2 If untreated, this disorder follows a chronic, inexorable course, usually characterized by progressive pancytopenia. Because of our success in the treatment of another B-cell neoplasm, chronic lymphocytic leukemia, with the deoxyadenosine analogue 2-chlorodeoxyadenosine,3 we have now undertaken a trial of this agent in hairy-cell leukemia. An adenosine deaminase—resistant purine analogue, 2-chlorodeoxyadenosine selectively accumulates as the 5′–triphosphate derivative in cells rich in deoxycytidine kinase. The cytotoxic activity of 2-chlorodeoxyadenosine is independent of cell division.4 Presumably because of its high… © 1990, Massachusetts Medical Society. All rights reserved.
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页码:1117 / 1121
页数:5
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