The Normalised Acute Rejection Score in the First Year Post Transplant and Its Association with CLAD

Abstract

<h3>Purpose</h3> The Acute Rejection Score (A-score) is a measure of the burden of acute cellular rejection (ACR) over time in lung transplant (Ltx) recipients which is often incorporated into multivariate analyses assessing LTx outcomes. We aim to assess the correlation between A-score at 6 and 12 months post Ltx and chronic lung allograft dysfunction (CLAD). <h3>Methods</h3> We performed a retrospective cohort analysis on adult 1^st double LTx recipients from January 2003 to March 2018, with minimum 6 months of follow-up and 1 or more evaluable transbronchial biopsies (TBBX) in the 1^st year post Ltx. A-score was calculated at 6 months (approximated as 210 days) and 1 year (400 days) post-LTx as the sum of all ACR histologic A-grades, divided by the number of TBBX up to that time point. AX grade biopsies were excluded from the calculation. CLAD was determined according to 2019 ISHLT guidelines. Kaplan-Meier curves were compared using the Log-Rank test. <h3>Results</h3> Of 828 1^st double lung transplants, 31 were excluded with less than 6 months of follow-up and 23 had no evaluable biopsies in the first year post Ltx (final n=774). Mean follow-up was 2102 days to graft failure (death or retransplant) or last available pulmonary function test. 345 patients (45%) developed CLAD. Mean A-score was 0.37 and 0.32 at 210 and 400 days, respectively; median non-zero A-score was 0.5 and 0.4. Kaplan-Meier curves comparing A-score 0 with scores above and below the median were not significantly different (p=0.08 and 0.78 for 210 and 400 days) (Figure A,B). Log-rank comparison of only non-zero groups was not significant (p=0.78 and 0.93 at 210 and 400 days). <h3>Conclusion</h3> A-score at 210 and 400 days post Ltx, when setting a cutoff at the median, is not significantly associated with CLAD. Further study with Cox proportional hazard modelling of the A-score as a continuous and time-dependent variable will be conducted to assess the impact on the risk of CLAD.