Comparison of Three Tacrolimus-Based Immunosuppressive Regimens in Lung Transplantation (original) (raw)
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Immunosuppressive therapy in lung transplantation: state of the art
European Journal of Cardio-Thoracic Surgery, 2009
The coming of age of lung transplantation is accompanied by an immunosuppressive armamentarium that has been brought forward from other transplant indications. Widely employed on the basis of few small randomized studies, and mostly single-center experience or empirical expert knowledge, anti-rejection therapeutic strategies in pulmonary transplantation have hardly been rigorously evaluated in large-scale prospective international trials. This review compiles the available findings on the use of current immunosuppressants in clinical lung transplantation, accentuating high level-of-evidence study results. Reporting on recent meeting and registry data, and assembling ongoing relevant trials from international databases, this article serves as an update on the state of the art of immunosuppression in lung transplantation.
New immunosuppressive regimens in lung transplantation
European Respiratory Journal, 1997
Survival after lung transplantation is less than 50% after 5 yrs and is limited by infection and obliterative bronchiolitis. There is, therefore, a need for new immunosuppressive regimens if we are to attempt to improve long-term survival. Several trials in lung transplantation of new immunosuppressive agents are in the planning stages.
Immunosuppressive strategies in lung transplantation
Annals of Translational Medicine, 2020
Lung transplantation is a viable option for those with end-stage lung disease which is evidenced by the continued increase in the number of lung transplantations worldwide. However, patients and clinicians are constantly faced with acute and chronic rejection, infectious complications, drug toxicities, and malignancies throughout the lifetime of the lung transplant recipient. Conventional maintenance immunosuppression therapy consisting of a calcineurin inhibitor (CNI), anti-metabolite, and corticosteroids have become the standard regimen but newer agents and modalities continue to be developed. Here we will review induction agents, maintenance immunosuppressives, adjunctive therapies and other strategies to improve long-term outcomes.
European Journal of Cardio-Thoracic Surgery, 2010
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 2 h prior to skin incision. Intraoperatively, 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 À1 ). Pulmonary function tests were performed frequently and daily after discharge by means of a self-measuring device (daily forced expiratory volume in 1 s (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 AE 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. #
Immunosuppression for lung transplant recipients
Current Respiratory Care Reports, 2014
The choices and extent of immunosuppression critically affect subsequent infection and rejection profiles after lung transplantation (LTx). Evidence does not support a particular induction strategy. Typically, a three drug regimen of a calcineurin inhibitor, cell cycle inhibitor, and corticosteroids provide LTx maintenance immunosuppression. Other agents (including mTOR inhibitors), and other routes of administration (sublingual or inhaled) tend to be held back for specific clinical problems. Treatment of acute cellular rejection with high dose corticosteroids is usually successful. By contrast, treatment of antibody-mediated rejection is problematic. It requires a combination of high dose corticosteroids, plasmapheresis, rituximab, and intravenous immunoglobulin. Chronic lung rejection is a particular challenge to treat. It is generally stated that any change in immunosuppression can lead to an apparent stabilization. Azithromycin and statins have some efficacy when used early. The current review aims to highlight the rationale for current immunosuppressive choices and draw attention to recent trends and developments.
Immunosupressive therapy in the lung transplant recipient
2015
Lung transplantation has become a life-saving procedure for individuals with variety of end-stage respiratory diseases. Optimal immunosuppression remains the key to long-term graft survivival. The protocols for immunosuppressive therapy following lung transplantation can be divided into three general categories: induction, maintenance, and treatment of rejection. The goal of induction therapy is to provide intense immunosuppression in the early post-transplantation period, when the risk of allograft rejection is the highest. Induction agents primarily target T lymphocytes, which are considered the effector cells in cell-mediated rejection. Current maintenance therapy typically includes a calcineurin inhibitor, nucleotide blocking agent and corticosteroid. Pulse steroids are generally the first treatment of acute cellular rejection. Therapeutic modalities for treatment of refractory cellular rejection include switch from cyclosporine to tacrolimus, use of lymphocyte depleting agents,...