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Previous Volume 342:613-619 March 2, 2000 Number 9 Next

	Full Text PDF Editorial by Carpenter, C. B. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Alloantigen-activated T cells express the high-affinity interleukin-2 receptor. Specific blockade of this receptor with the human IgG1 monoclonal antibody daclizumab may prevent rejection of allografts after cardiac transplantation without inducing global immunosuppression.

Methods We randomly assigned 55 nonsensitized patients undergoing a first cardiac transplantation to receive either induction therapy with daclizumab (1.0 mg per kilogram of body weight), given intravenously within 24 hours after cardiac transplantation and every two weeks thereafter, for a total of five doses, or generalized immunosuppressive therapy. Concomitant immunosuppression was achieved in both groups with cyclosporine, mycophenolate mofetil, and prednisone. The primary end points were the incidence and severity of acute rejection, and the length of time to a first episode of biopsy-confirmed rejection.

Results Of the 55 patients in the study, 28 were randomly assigned to receive daclizumab and 27 served as the control group. During induction therapy, the mean frequency of acute rejection episodes (defined as a histologic grade of 2 or higher according to the classification of the International Society of Heart and Lung Transplants) was 0.64 per patient in the control group and 0.19 per patient in the daclizumab group (P=0.02). Acute rejection developed in 17 of 27 patients in the control group (63 percent), as compared with 5 of 28 patients in the daclizumab group (18 percent; relative risk, 2.8; 95 percent confidence interval, 1.1 to 7.4; P=0.04). Throughout follow-up, there were nine patients with episodes of acute rejection of histologic grade 3 in the control group, as compared with two in the daclizumab group (P= 0.03), and the time to a first episode of rejection was significantly longer in the daclizumab group (P=0.04). There were no adverse reactions to daclizumab and no significant differences between the groups in the incidence of infection or cancer during follow-up.

Conclusions Induction therapy with daclizumab safely reduces the frequency and severity of cardiac-allograft rejection during the induction period.

Source Information

From the Divisions of Cardiology (A.B., B.D.G., D.M.M.) and Circulatory Physiology (A.B., D.M.M.) and the Department of Surgery (S.I., K.L., M.D., E.M.B., N.E.), Columbia–Presbyterian Medical Center, New York.

Address reprint requests to Dr. Beniaminovitz at 177 Fort Washington Ave., MHB 5-435, New York, NY 10032, or at ab49{at}columbia.edu.

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