Dissecting Serial Immune Response Stages of Chronic Rejection after Murine Orthotopic Lung Transplantation

Abstract

Purpose: Chronic allograft dysfunction (CLAD) limits survival after lung transplantation (LT), affecting 50% by 5-years and 75% by 10 years. Long-term survival (≥10 years) is seen in 35-40% after LT. While 10-15% of patients survive ≥10 years without CLAD, the reasons remain unclear. Our aim was to determine clinical factors that differ between long-term survivors with and without CLAD Methods: This was a single-center retrospective cohort study of all first LT performed between 1983 and 2010. Re-transplants and those without follow-up data were excluded. CLAD was adjudicated by ISHLT criteria in patients with ≥ 4 pulmonary function tests (PFTs). Associations of clinical variables with CLAD-free status were assessed using univariate logistic regression Results: 1110 patients underwent primary LT in the study period. 1-year survival was 79.5 (882/1110). 32.2% (357/1110) survived ≥10 years, and of those with sufficient PFTs, 10.6% (118/348) were long-term CLADfree survivors. 73.7% (87/357) of this cohort are still alive at a median follow-up of 12.49 (IQR 11.3-14.85) years. Among very long-term survivors (≥20 years; n=49) with sufficient PFTs, 83% were CLAD-free at a median of 23.3 (IQR 21.1-25.87) years. Shorter ischemic time, lower donor age, indication for transplant, higher baseline total lung capacity and baseline renal function, and absence of gastroparesis, major infections and treatment for acute rejection were all associated with ≥10-year CLAD-free survival. Compared to long-term survivors without CLAD, those with CLAD had higher mortality (<0.001) and skin cancers on follow-up Conclusion: We identified clinical variables associated with ≥10-year CLAD-free survival in our cohort. We will perform multiple regression and compare this cohort with those surviving 1 to 5 years post-LT using Cox proportional hazards model. We aim to optimize recipient-allograft matching leading to better long-term CLAD-free survival.