Induction therapy in lung transplantation: a prospective, controlled clinical trial comparing OKT3, anti-thymocyte globulin, and daclizumab

J Heart Lung Transplant. 2001 Dec;20(12):1282-90. doi: 10.1016/s1053-2498(01)00356-4.

Abstract

Background: Because acute rejection is associated with inferior outcomes in lung transplantation, we have routinely employed OKT3, anti-thymocyte globulin (ATG), or daclizumab as adjuncts to reduce rejection.

Method: We performed a 4-year prospective, controlled clinical trial of these 3 therapies to determine differences in post-operative infection, rejection, survival, and bronchiolitis obliterans syndrome (BOS). Eighty-seven consecutive lung transplant patients received OKT3 (n = 30), ATG (n = 34), and daclizumab (n = 23) as induction agents. The groups had similar demographics and immunosuppression protocols differing only in induction agents used.

Results: No differences were observed in immediate post-operative outcomes such as length of hospitalization, ICU stay, or time on ventilators. Twelve months post-transplant, OKT3 had more infections per patient than the other agents, a difference that only became significant 2 months post-operatively (p = 0.009). The most common infection was bacterial and OKT3 had more bacterial infections than any other agent. Daclizumab had more patients remain infection free in the first year (p = 0.02), having no fungal infections and a low rate of viral infections. No patient receiving daclizumab developed drug specific side-effects. Only those patients with episodes of acute rejection developed BOS. There were no significant differences in the freedom from acute rejection or BOS between the groups. The 2-year survival for the entire cohort was 68%, with no differences observed in patient survival.

Conclusions: This study again reveals the importance of acute rejection in the subsequent development of BOS. Although daclizumab offers a low risk of post-transplant infection and drug specific side-effects, no drug is superior in delaying rejection or BOS or in prolonging long-term survival.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal, Humanized
  • Antilymphocyte Serum / administration & dosage*
  • Antilymphocyte Serum / adverse effects
  • Bronchiolitis Obliterans / immunology
  • Daclizumab
  • Female
  • Follow-Up Studies
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control*
  • Humans
  • Immunoglobulin G / administration & dosage*
  • Immunoglobulin G / adverse effects
  • Immunosuppressive Agents / administration & dosage*
  • Lung Transplantation / immunology*
  • Male
  • Middle Aged
  • Muromonab-CD3 / administration & dosage*
  • Muromonab-CD3 / adverse effects
  • Opportunistic Infections / immunology
  • Risk Factors

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antilymphocyte Serum
  • Immunoglobulin G
  • Immunosuppressive Agents
  • Muromonab-CD3
  • Daclizumab