CYTOLYTIC THERAPY FOR THE BRONCHIOLITIS OBLITERANS SYNDROME COMPLICATING LUNG TRANSPLANTATION

The bronchiolitis obliterans syndrome (BOS) is the major cause of late morbidity and mortality after lung transplant (LTx). Previous studies suggest cytolytic therapy may be effective for the BOS but this thera py has not been proved effective or safe. Method: A retrospective stud y of a predetermined treatment regimen to determine if the rate of fal l in FEV(1) can be reduced by corticosteroids and cytolytic therapy, S ince August 1992, 10 of 65 long-term survivors of LTx (5 men, 5 women; mean age 36+/-10 years) developed BOS, All had previously had lymphoc yte immune globulin, antithymocyte globulin (equine) (ATGAM sterile so lution; Upjohn Pty Ltd; Sydney, Australia) induction therapy and corti costeroid avoidance for the first 7 to 10 days post-LTx. Therapy for t he BOS was initiated with pulse methylprednisolone and ATGAM (aiming f or an absolute CD3 count of less than or equal to 100 cells per microl iter for 5 days). ATGAM therapy was initiated at a mean 657+/-323 days post-LTx. Subsequent follow-up has been for 310+/-110 days (range, 16 3 to 530 days). Results: Nine of ten patients had a response with tole rable side effects. Preintervention, there was a linear fall in FEV(1) of 0.22+/-0.15% predicted FEV(1) per day (mean+/-SD) (range, 0.06 to 0.56%) compared,vith a postintervention linear fall of 0.036+/-0.019% predicted per day (range, 0 to 0.13%) (paired t test; p<0.005), This e ffect is sustained over the follow-up period. Conclusion: The fall off in FEV(1) that characterizes the BOS may be altered usefully by augme nted immunotherapy. This effect can be rapid and sustained although it is neither completely arrested nor ever reversed. These data are prel iminary but encourage a randomized control trial in the BOS.