DELAYED DEVELOPMENT OF OBLITERATIVE BRONCHIOLITIS SYNDROME WITH OKT3 AFTER UNILATERAL LUNG TRANSPLANTATION - A PLEA FOR MULTICENTER IMMUNOSUPPRESSIVE TRIALS

There is no consensus regarding the optimal induction immunosuppressio n regimen after lung transplantation (LT). In addition to the potentia l benefit of a reduced incidence of early acute allograft rejection, c ytolytic induction immunosuppression may impact on long-term allograft function. We retrospectively assessed our incidence of obliterative b ronchiolitis syndrome (OBS) stages Ia and IIa in LT survivors given mi o different cytolytic induction immunosuppression regimens: (between M arch 1989 and October 1990) OKT3 (5 mg/d) x 10 to 14 days (n = 11) vs (between November 1990 and April 1993) Minnesota antilymphocyte globul in (MALG) (10 to 15 mg/kg/dx5 to 7 days. Cyclosporine (CSA) (whole blo od polyclonal assay=600 to 800 ng/mL), azathioprine (1 to 2 mg/kg/d), and maintenance prednisone (0.2 mg/kg/d) were similar. Surveillance sp irometry was performed monthly, in accordance with accepted American T horacic Society criteria. Fiberoptic bronchoscopy with transbronchial biopsies (TBBs) were performed for clinical indications. Surveillance TBBs were not pet-formed during the era of this study. As defined by t he ISHLT ''Working Formulation for the Standardization of Nomenclature and for Clinical Staging of Chronic Dysfunction in Lung Allografts,'' latencies to development of OBS stages Ia and IIa were determined by Kaplan-Meir analysis. Stepwise regression (Cox proportional hazards mo del) was performed for the variables: cytolytic induction regimen, epi sodes cytomegalovirus (CMV) pneumonitis, episodes CMV infection, serol ogic CMV donor (+): recipient (-) mismatch, prior pregnancy, HLA (A,B, DR+/-DQ) mismatches, episodes greater than grade Al acute cellular rej ection (ACR). We found that the OKT3 cohort experienced longer latenci es for OBS stages fa and IIa. Latencies to OBS stage Ia for OKT3 vs MA LG were 962+/-65 vs 354+/-85 days (X+/-SEM) respectively. Brookmeyer-C rowley 95% confidence intervals for median latencies were 744 to 1,180 vs 266 to 510 days for OKT3 vs MALG, respectively. The Cox model was significant only for the variable of the induction cytolytic immunosup pression regimen (p=0.0015). By physiologic criteria, a longer course of OKT3 appeared superior to the short-course MALG protocol in delayin g chronic lung allograft dysfunction. These effects may be related eit her to inherent differences in the antilymphocyte preparations or, alt ernatively, the difference in duration of treatment between groups. Su rveillance TBB and treatment of detected occult ACR may serve to negat e the observed differences in latencies for OBS.