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 therapy has not been proved effective or safe.

A retrospective study of a predetermined treatment regimen to determine if the rate of fall in FEV1 can be reduced by corticosteroids and cytolytic therapy. Since August 1992, 10 to 65 long-term survivors of LTx (5 men, 5 women; mean age 36 +/- 10 years) developed BOS. All had previously had lymphocyte immune globulin, antithymocyte globulin (equine) (ATGAM sterile solution; Upjohn Pty Ltd; Sydney, Australia) induction therapy and corticosteroid avoidance for the first 7 to 10 days post-LTx. Therapy for the BOS was initiated with pulse methylprednisolone and ATGAM (aiming for an absolute CD3 count of < or - 100 cells per microliter 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, 163 to 530 days).

Nine of ten patients had a response with tolerable side effects. Preintervention, there was a linear fall in FEV1 of 0.22 +/- 0.15% predicted FEV1 per day (mean +/- SD) (range, 0.06 to 0.56%) compared with a postintervention linear fall of 0.036 +/- 0.019% predicted per day (range, 0 to 0.13%) (paired t test; p<0.005). This effect is sustained over the follow-up period.

The fall off in FEV1 that characterizes the BOS may be altered usefully by augmented immunotherapy. This effect can be rapid and sustained although it is neither completely arrested nor ever reversed. These data are preliminary but encourage a randomized control trial in the BOS.