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


METHODS
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.
Brock
M V
MV
Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Borja
M C
MC
Ferber
L
L
Orens
J B
JB
Anzcek
R A
RA
Krishnan
J
J
Yang
S C
SC
Conte
J V
JV
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000961:Antilymphocyte Serum / Q000008:administration & dosage* / Q000009:adverse effects; D001989:Bronchiolitis Obliterans / Q000276:immunology; D000077561:Daclizumab; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000009:adverse effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016040:Lung Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000008:administration & dosage* / Q000009:adverse effects; D009894:Opportunistic Infections / Q000276:immunology; D012307:Risk Factors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000961:Antilymphocyte Serum; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D016853:Muromonab-CD3; D000077561:Daclizumab