Low rate of acute lung allograft rejection after the use of daclizumab, an interleukin 2 receptor antibody.

Background. The incidence and the severity of acute lung allograft rejection has been linked to the development of bronchiolitis obliterans syndrome. Therefore, we investigated the effects of daclizumab, a humanized monoclonal antibody directed against the alpha subunit of the interleukin 2 receptor, in reducing acute rejection after transplantation. Methods. We retrospectively evaluated 27 patients who received daclizumab as induction immunosuppression and compared them with a historical control group of 34 patients. Both groups received similar immunosuppressive regimens involving tacrolimus, prednisone, and either azathioprine or mycophenolate mofetil. All patients received cytomegalovirus and aspergillus prophylaxis. Results. Twenty-one patients in the control group and 22 patients in the daclizumab group were available for analysis at 6 months after lung transplantation. Ten (48%) patients in the control group had at least grade 2 acute rejection compared with four (18%) in the daclizumab group (P<0.04). The incidence of infection was similar in both groups. One patient in each group developed posttransplant lymphoproliferative disease. Conclusion. Therapy with daclizumab resulted in a significant decrease in the incidence of grade 2 or greater acute rejection after lung transplantation compared with historical controls. There seems to be no increase in the incidence of adverse effects in the patients treated with daclizumab. Although lung transplantation has become an accepted therapy to improve life span and quality of life for patients with advanced lung disease, outcomes continue to be marred by acute rejection and bronchiolitis obliterans syndrome (BOS) (1, 2). Currently used regimens of immunosuppression still result in high rates of acute rejection after lung transplantation, with 50 ‐70% of lung transplant recipients often suffering at least one episode of rejection (2, 8). BOS is the single largest cause of death more than 1 year after lung transplantation, and its occurrence is consistently linked to the number and severity of previous acute rejection episodes (3‐7). Daclizumab is a novel, humanized monoclonal antibody directed against the alpha subunit of the interleukin (IL)-2 receptor (CD25). It has been shown to reduce acute allograft rejection in renal transplantation with minimal side effects. In separate studies by Nashan et al. (9) and Vincenti et al. (10), the investigators demonstrated a significant reduction in the incidence of acute renal allograft rejection in the patients who received daclizumab. They also demonstrated no significant side effects due to the therapy. Daclizumab has also been used with promising results in heart transplantation (11). Given the increase in morbidity and mortality associated with acute rejection in lung transplantation, we elected to use daclizumab as induction therapy in addition to our current immunosuppressive regimen. We hypothesized that daclizumab would reduce the incidence and severity of acute rejection in lung transplant recipients compared with those given no induction therapy. We further hypothesized that the incidence of cytomegalovirus (CMV) and aspergillus infections would be comparable between the patients who received daclizumab and those who did not.