Induction immunosuppression for lung transplantation with OKT3

The use of OKT3, an anti-CD3 monoclonal antibody, for immunosuppressive therapy for lung transplantation has been restricted because of concerns regarding infectious risk and cardiopulmonary instability after its administration.

Fifty-two patients received OKT3 (5 mg/d intravenously for 10 days) for induction of immunosuppressive therapy, along with azathioprine (1.5 mg x kg(-1) x d(-1) intravenously) and enteral cyclosporine (12 mg x kg(-1) x d(-1)). Maintenance steroid therapy was begun on postoperative day 8. Prophylactic antifungal therapy (fluconazole or amphotericin B) and ganciclovir was used in all patients. Serial transbronchial biopsy and measurements of pulmonary function were used to assess patients for evidence of infection or rejection. Cytomegalovirus infection was diagnosed by biopsy or the presence of cytomegalovirus antigenemia.

The 30-day mortality rate was 4%; the in-hospital mortality rate was 8%. Acute graft failure was seen in 6 patients. The median length of intubation was 5 days, and the median hospital stay was 30 days. Systemic and pulmonary artery systolic pressures, cardiac index, and ratio of arterial partial oxygen pressure to fraction of inspired oxygen showed no significant alteration after OKT3 dosage. Gram-negative pulmonary infections were identified in 12 patients. Aspergillus infection was seen in 7 patients. Cytomegalovirus infection in 8 patients responded to ganciclovir and did not affect mortality. Respiratory syncytial viral infection was seen in 7 patients. Acute rejection was never seen during OKT3 administration. No episodes of acute rejection were identified in 14 patients at any time postoperatively. In the remainder, episodes of acute rejection responded to steroid or antithymocyte globulin therapy. At a median length of follow-up of 31 months, freedom from obliterative bronchiolitis was 69%+/-9% at 36 months. The overall survival rate was 88%+/-5% at 12 months, 82%+/-6% at 24 months, and 74%+/-7% at 36 months after transplantation.

OKT3 is a safe and effective agent for induction immunosuppressive therapy in lung transplant recipients that limits the incidence of acute rejection and may decrease the incidence of obliterative bronchiolitis.