Survival After Lung Transplantation in Europe - Clad as Major Cause of Death

Abstract

<h3>Purpose</h3> Lung transplantation (LTX) outcomes are poor in comparison to other solid organ transplantations. Our aim was to review survival, leading chronic complications, and major causes of death in Europe. A particular focus is put on Chronic Lung Allograft Dysfunction (CLAD) and its trends. <h3>Methods</h3> There is no dedicated European registry on lung transplantation, outcomes, and complications. Therefore, accessible data from ISHLT registry with focus on the European continent, European Registries and German Quality report were screened for lung transplantation survival data. Furthermore, a dedicated literature research on chronic complications following LTX and particularly CLAD was performed with focus on Europe. In a further step, clinical trial registries were screened for advanced trials addressing the leading form of CLAD - obstructive phenotype - Bronchiolitis Obliterans Syndrome (CLAD-BOS). <h3>Results</h3> Survival rate for LTX reaches 83.2% and 71% at 1 and 3 years, based on 3502 cases included between 2013 and 2016 in the ISHLT registry - European Continent, under exclusion of retransplant. Eurotransplant data from 2012 to 2016 comprising 3053 LTX from Austria, Belgium, Germany, and the Netherlands state survival rates of 83.5%, 76.8% and 62.5% at year 1, 2 and 5. Yet, pan-European data are lacking. Some large monocentric European studies report CLAD rates ranging from 38% at 3 years to 44% at longer follow-up. These findings are in line with US data. CLAD-BOS represented consistently the most prevalent phenotype, up to 80% of all CLAD cases. Although no dedicated European registry data are available, monocentric studies pinpoint CLAD as the single largest cause of death post-LTX. Within CLAD, BOS phenotype accounts for two-thirds of deaths based on reported autopsy analysis. Currently, two substances targeting CLAD-BOS are in phase 3 clinical investigation in Europe. <h3>Conclusion</h3> In Europe, 3-year post-lung transplantation survival is around 70% and 5-year survival at 63%. CLAD is consistently the most prevalent and fatal complication in lung transplant recipients. CLAD-BOS is the most frequent phenotype. New treatments to address chronic graft failure and primary cause of death in LTX, namely CLAD-BOS, are needed. Currently two therapeutic approaches are under investigation in phase 3 clinical trials aiming at CLAD-BOS in Europe.