Original Articles
Induction immunosuppression for lung transplantation with OKT3

Presented at the Thirty-third Annual Meeting of The Society of Thoracic Surgeons, San Diego, CA, Feb 3–5, 1997.
https://doi.org/10.1016/S0003-4975(98)01308-3Get rights and content

Abstract

Background. 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.

Methods. Fifty-two patients received OKT3 (5 mg/d intravenously for 10 days) for induction of immunosuppressive therapy, along with azathioprine (1.5 mg · kg−1 · d−1 intravenously) and enteral cyclosporine (12 mg · kg−1 · 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.

Results. 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.

Conclusions. 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.

Section snippets

Patient population

Fifty-two lung transplant recipients undergoing operation at the Massachusetts General Hospital from August 1990 to August 1996 received OKT3 as induction immunosuppressive therapy. Recipient diagnoses included pulmonary parenchymal disease in 31 (chronic obstructive pulmonary disease in 17, α1-antitrypsin deficiency in 5, lymphangioleiomyomatosis in 2, idiopathic pulmonary fibrosis in 3, desquamative interstitial pneumentis in 3, scarceidosis in 1); septic lung disease in 15 (cystic fibrosis

Results

Single-lung transplantation was performed in 29 patients, and double-lung transplantation, using a sequential single-lung transplantation technique, was performed in 23 patients. Average ischemic time (mean ± standard deviation) was 240 ± 80 minutes for one lung and 380 ± 56 minutes for the second lung. Cardiopulmonary bypass was required in 10 patients, including all 6 patients with pulmonary vascular disease, 2 patients with cystic fibrosis, and 1 patient with restrictive lung disease.

Comment

The administration of OKT3 results in the activation of complement and the release of lymphokines, which have been reported to have profound effects on cardiopulmonary function 3, 5, 7. In our experience, some mild elevations in pulmonary artery systolic pressure were seen, accompanied by a mild reduction in oxygenation and pyrexia within 6 hours of administration of the first dose. These effects were self-limited and resolved within 12 hours, although they did recur, to a much lesser extent,

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    Copyright © 1999 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.