Induction therapy in lung transplantation: initial single-center experience comparing daclizumab and antithymocyte globulin.

UNLABELLED: Acute and chronic rejection remain unresolved problems after lung transplantation, despite heavy multidrug immunosuppression. Because acute rejection is associated with inferior outcomes in lung transplantation, we have routinely employed antithymocyte globulin (ATG) or daclizumab as adjuncts to reduce the incidence of rejection episodes. METHODS: We performed a controlled clinical trial of the two therapies to evaluate differences in postoperative rejection, infection, bronchiolitis obliterans syndrome (BOS) and host survival. Twenty-five consecutive lung transplant patients received ATG (n = 12; group 1) or daclizumab (n = 13; group 2) as an induction agent. The groups showed similar demographics and immunosuppression protocols, differ only in induction agent. RESULTS: No differences were observed in the immediate postoperative outcomes, such as length of hospitalization, ICU stay, or time on ventilator. There were no significant differences in the number of episodes of acute rejection, freedom from BOS, or infections. Freedom from acute rejection was significantly greater with daclizumab than with ATG (P = .037). The 1-year survival for group 1 was 67% and for group 2, 77% (P = .584). CONCLUSIONS: Daclizumab constitutes a safe and effective form of induction immunosuppressive therapy. Using a two-dose administration schedule, daclizumab prolonged the time without acute rejection compared to ATG. The differences in the incidence of infectious complications, acute rejection, or BOS as well as the short-term or long-term results were not significantly different. The results of the study justify the further use of daclizumab as an induction agent in patients following lung transplantation.

Initial single-center experience with sirolimus after lung transplantation.

BACKGROUND: Standard immunosuppression after lung transplantation includes calcineurin inhibitors, mycophenolate mofetil, and steroids. Long-term survivors of lung transplantation are often confronted with chronic kidney disease, by definition related to the intake of calcineurin inhibitors. Sirolimus has been increasingly proposed as an alternative immunosuppressive agent due to its absence of nephrotoxicity, which could be used in selected patients. METHODS: We prospectively administered sirolimus as an alternative to calcineurin inhibitors in 10 lung transplantation recipients with persistent drug nephrotoxicity. They were switched from tacrolimus to sirolimus. Four patients also had bronchiolitis obliterans syndrome. The conversion scheme consisted of an immediate stop of tacrolimus and an 6 to 8-mg loading dose of sirolimus, followed by 4 mg/d. After 5 days, the sirolimus dose was adjusted to maintain trough levels between 12 and 18 ng/mL or 6 and 12 ng/mL for combined sirolimus and tacrolimus. Patients were monitored for renal and graft function as well as clinical status. RESULTS: A significant decrease in creatinine was observed after 1 week of treatment (P = .011). Azotemia decreased after 1 month, remaining stable (P < .01). Pulmonary function tests did not show significant modification from before sirolimus, inception in patients with or without bronchiolitis obliterans syndrome. There were seven infections. One patient died of complications related to bronchiolitis obliterans. CONCLUSION: Sirolimus was a useful alternative immunosuppressant, allowing significant tacrolimus withdrawal in transplant recipients with renal impairment. Sirolimus administration allowed recovery of renal function with low morbidity; it was useful for rescue of chronic renal impairment after lung transplantation.