Shorter telomere length following lung transplantation is associated with clinically significant leukopenia and decreased chronic lung allograft dysfunction-free survival

Abstract

Patients with short telomeres and interstitial lung disease may have decreased chronic lung allograft dysfunction (CLAD)-free survival following lung transplantation. The relationship between post-transplant telomere length and outcomes following lung transplantation has not been characterised among all recipients, regardless of native lung disease.This was a single-centre prospective cohort study. Consenting transplant recipients had their telomere length measured using quantitative real-time PCR assays on peripheral blood collected at the time of surveillance bronchoscopy. We assessed the association between early post-transplant telomere length (as measured in the first 100 days) and CLAD-free survival, time to clinically significant leukopenia, cytomegalovirus (CMV) viraemia, chronic kidney disease, and acute cellular rejection. We also assessed the association between rate of telomere shortening and CLAD-free survival.Telomere lengths were available for 98 out of 215 (45.6%) recipients who underwent lung transplant during the study period (median measurement per patient=2 (interquartile range, 1–3)). Shorter telomere length was associated with decreased CLAD-free survival (hazard ratio (HR)=1.24; 95% CI=1.03–1.48; p=0.02), leukopenia requiring granulocyte colony-stimulating factor (HR=1.17, 95% CI=1.01–1.35, p=0.03), and CMV viraemia among CMV-mismatch recipients (HR=4.04, 95% CI=1.05–15.5, p=0.04). Telomere length was not associated with acute cellular rejection or chronic kidney disease. Recipients with more rapid loss in telomere length (defined as the highest tertile of telomere shortening) did not have worse subsequent CLAD-free survival than those without rapid loss (HR=1.38, 95% CI=0.27–7.01, p=0.70).Shorter early post-transplant telomere length is associated with decreased CLAD-free survival and clinically significant leukopenia in lung transplant recipients, regardless of native lung disease.