Two-center-results of conversion to Sirolimus and Mycophenolate Mofetil (MMF) in lung transplant recipients suffering from BOS

Background: Bronchiolitis obliterans Syndrome (BOS) is a major problem in lung and heart-lung transplantation (LTx/HLTx). Rapamycin-derivates showed in animal models a remarkable efficacy in the prevention of BOS. We report our clinical experience in converting LTx/HLTx-recipients from a conventional immunosuppressive regimen to a rapamycin-based immunosuppression, when BOS was diagnosed.

Material and Methods: 4 LTx- and 6 HLTx-recipients (7 men; 0.9 to 8 years after transplantation) with CNI-based immunosuppression (plus MMF) in whom BOS was diagnosed (biopsy-proven) were included in the study. Mean patient age was 35±9 years (range 17–62 years). Sirolimus (a rapamyin derivate) was started with 2mg and continued adjusted to according target trough levels (8–14 ng/mL for Sirolimus). Subsequently, the CNIs were tapered down and finally stopped. Clinical follow up included lung function tests, microbiological screening, chest X-ray/CT and laboratory studies.

Results: No acute rejection episode occurred during the study period. Graft function remained stable in only 3 patients. Mean FEV1 decreased after a mean follow up of 12±8 months: from 2.1±0.5l/min prior conversion to 1.3±0.6l/min after conversion (p=0.02). The incidence of infection was 3.2±0.5 infections/pat. year after conversion. One patient was reconverted due to non-compliance resulting in severe pneumonia. However, 2 of 10 patients died due to ongoing BOS awaiting retransplantation.

Conclusions: After BOS is diagnosed, conversion to Sirolimus and MMF can stabilize graft function only in a small part of the converted patients. Whether conversion to Sirolimus-based immunosuppression can really diminish the progress of BOS has to be investigated in larger, randomized trials. Therefore, earlier administration of Sirolimus-based immunosuppression might be a more promising approach.