A Randomized, Controlled Trial of Daclizumab vs Anti-thymocyte Globulin Induction for Lung Transplantation John C. Mullen, MD, a Antigone Oreopoulos, MSc, a Dale C. Lien, MD, c Michael J. Bentley, BSc, a Dennis L. Modry, MD, a Ken Stewart, MD, b Timothy L. Winton, MD, b Kathy Jackson, BNSc, d Karen Doucette, MD, f Jutta Preiksaitis, MD, f and Phil F. Halloran, MD e Background: Rejection remains a significant cause of morbidity and mortality after lung transplantation. The purpose of this study was to test the efficacy and safety of daclizumab (DZM) vs anti-thymocyte globulin (ATG) as a component of induction therapy. Methods: Fifty adults undergoing lung transplantation were randomized to receive either ATG or DZM during induction therapy. Patients were followed for 1 year after transplant. Results: Although there was no significant difference in the number of acute or chronic rejections between groups, there was a trend toward a delay in time to first acute rejection with DZM induction. Average absolute lymphocytes and average platelet count were significantly higher in the DZM group. Cytomegalovirus (CMV) serology mismatch was higher in the DZM group (7 vs 1, p = 0.05). The DZM group had a greater number of infections (83 vs 47, p = 0.02); however, the number of CMV infections was also significantly greater (18 vs 6, p = 0.03), corresponding to a higher incidence of CMV mismatch. A cost analysis revealed no difference between total drug costs, intensive-care unit (ICU) costs and total hospital costs. One-year survival was 96% in the DZM group and 88% in the ATG group. Conclusions: DZM is a safe component of induction therapy in lung transplantation. In addition, DZM may prolong freedom from acute rejection. Significant infections were more frequent in the DZM group, but this was likely due to a higher incidence of CMV mismatch. Both methods of induction therapy worked well, with excellent 1-year survival. J Heart Lung Transplant 2007;26:504 –10. Copyright © 2007 by the International Society for Heart and Lung Transplantation. Although lung transplantation has become an estab- lished life-saving intervention for patients with end- stage pulmonary disease, outcomes continue to be compromised by allograft rejection and infection. 1 With the currently used immunosuppression regimens, 50% to 70% of recipients have at least one episode of rejection, 2,3 and 70% to 80% have at least one episode of infection during the first year. 4 To improve patient survival and quality of life, strategies have been devel- oped to minimize infection and rejection, including induction agents, as part of the immunosuppression regimen in the early post-operative period. Induction regimes consist of antibodies that exhibit protective effects from allograft rejection, administered during the immediate post-operative period when the risk of rejection is highest due to a high donor leuko- cyte load. 5 Daclizumab (DZM) is a novel compound for use as a component of induction therapy. This agent is a murine monoclonal antibody, directed at the alpha sub-unit of the interleukin-2 receptor (IL-2R) expressed on activated T lymphocytes. 6 Our current induction therapy includes T-lymphocyte inactivation through the administration of polyclonal anti-thymocyte globulin (ATG). There have been no reported randomized, con- trolled trials comparing DZM to ATG induction in lung transplantation. The purpose of this study was to compare these therapies in lung transplant recipients. METHODS All adults listed for single- or double-lung transplantation between July 2001 and March 2003 were considered for From the Divisions of a Cardiac Surgery and b Thoracic Surgery, and Departments of c Pulmonary Medicine, d Surgery, e Clinical Laboratory Medicine and f Infectious Diseases, University of Alberta, Edmonton, Alberta, Canada. Submitted May 19, 2006; revised January 4, 2007; accepted January 30, 2007. Presented in part at the 25th annual meeting of the International Society of Heart and Lung Transplantation, April 2005, Philadelphia, Pennsylvania. Supported by an unrestricted research grant from Hoffmann–La Roche. Data collection, analysis and manuscript preparation were conducted by the investigators in compliance with the protocol and independent of the sponsor. Reprint requests: John C. Mullen, MD, Department of Surgery, University of Alberta Hospital, 2D2.18 WC Mackenzie Health Sciences Centre, 8440 –112 Street, Edmonton, AB T6G 2B7, Canada. Tele- phone: 780-407-6327. Fax: 780-407-6752. E-mail: jmullen@ualberta.ca Copyright © 2007 by the International Society for Heart and Lung Transplantation. 1053-2498/07/$–see front matter. doi:10.1016/ j.healun.2007.01.032 504 IMMUNOSUPPRESSION