Preoperative introduction and maintenance immunosuppression therapy of oral-only tacrolimus, mycophenolate mofetil and steroids reduce acute rejection episodes after lung transplantation.

OBJECTIVE: Immunosuppression therapy in lung transplantation (LTX) remains unsatisfactory due to a high incidence of infection and frequent acute rejection (AR), leading to early onset of the bronchiolitis obliterans syndrome (BOS). The long-term success of LTX is limited by BOS, associated with marked morbidity and mortality. The strongest risk factor for BOS is frequent AR. Decreasing frequent AR episodes might lead to improved long-term survival following LTX.

METHODS: Despite the introduction of many novel agents, the basis of currently applied protocols remains a calcineurin inhibitor, that is, cyclosporine/tacrolimus (TAC). Eighty-two lung recipients received oral-only administered immunosuppression with oral TAC, mycophenolate mofetil (MMF) and intravenous (IV) methylprednisolone as introduction 2h prior to skin incision. Intra-operatively, patients received additional methylprednisolone prior to unclamping the pulmonary arteries. Postoperatively oral TAC/MMF and prednisolone were continued and trough levels closely monitored (target 8-12 ng ml(-1)). Pulmonary function tests were performed frequently and daily after discharge by means of a self-measuring device (daily forced expiratory volume in 1s (FEV(1))) as the major part of a close follow-up and monitoring programme. Trans-bronchial biopsies were rarely performed. Patient data were collected prospectively and stored in transplantation registries. LTX survival was analysed according to the Kaplan-Meier method.

RESULTS: The follow-up of the LTX patients through frequent ambulatory care unit visits and close monitoring of the immunosuppressive regimen and the medication response was 100% complete. The mean duration of observation per patient was 1.8 + or - 1.7 years (median 1.4, range: 0.0-6.4 years) and this study included 176.5 patient-related years of follow-up. The 1-, 3- and 5-year survival following LTX was 70%, 60% and 55%, respectively. Eight patients (10%) underwent high-dose intravenous (IV) bolus methylprednisolone treatment and taper for AR. Two additional patients developed BOS more than 4 years following LTX. The AR- and BOS-related mortality was 0% within the 7-year interval of LTX. Alterations in FEV(1) were associated with significant anastomotic airway and infectious complications, requiring frequent bronchoscopic interventions, stenting and laser therapy as well as frequent IV antibiotic treatment. The 30-day and in-hospital mortality of 19.5% was markedly related to primary graft failure and viral infection. Long-term survival was limited predominantly by cytomegalovirus (CMV) infection and sepsis.

CONCLUSIONS: Our results suggest that a standard immunosuppressive regimen of TAC and MMF orally administered and introduced prior to skin incision for LTX surgery and maintained long-term might reduce the incidence of acute and chronic rejection. Viral infections and not BOS seemed to be the limiting factor of long-term survival.