Determinants of survival after lung transplantation in telomerase-related gene mutation carriers: A retrospective cohort

Abstract

Carriers of germline telomerase‐related gene (TRG) mutations can show poor prognosis, with an increase in common hematological complications after lung transplantation (LT) for pulmonary fibrosis. The aim of this study was to describe the outcomes after LT in recipients carrying a germline TRG mutation and to identify the predictors of survival. In a multicenter cohort of LT patients, we retrospectively reviewed those carrying pathogenic TRG variations (n = 38; TERT, n = 23, TERC, n = 9, RTEL1, n = 6) between 2009 and 2018. The median age at LT was 54 years (interquartile range [IQR] 46–59); 68% were male and 71% had idiopathic pulmonary fibrosis. During the diagnosis of pulmonary fibrosis, 28 (74%) had a hematological disease, including eight with myelodysplasia. After a median follow‐up of 26 months (IQR 15–46), 38 patients received LT. The overall post‐LT median survival was 3.75 years (IQR 1.8‐NA). The risk of death after LT was increased for patients with myelodysplasia (HR 4.1 [95% CI 1.5–11.5]) or short telomere (HR 2.2 [1.0–5.0]) before LT. After LT, all patients had anemia, 66% had thrombocytopenia, and 39% had neutropenia. Chronic lung allograft dysfunction frequency was 29% at 4 years. The present findings support the use of LT in TRG mutation carriers without myelodysplasia. Hematological evaluation should be systematically performed before LT.

Interstitial lung diseases associated with mutations of poly(A)‐specific ribonuclease: A multicentre retrospective study

“…36,37 However, the mean overall survival is >5 years after lung transplantation in the absence of myelodysplasia before lung transplantation. 38,39 We observed only one death in the six patients who underwent lung transplantation, with a median follow-up of 21 months, and none showed myelodysplasia or liver cirrhosis.…”

Short peripheral blood leukocyte telomere length in rheumatoid arthritis-interstitial lung disease

“…Individuals with other ILDs and shortened TL and/or telomerase mutations have been shown to have more rapid progression, 6 shorter transplant-free survival, 9 and worse transplant-related outcomes. 10 It will be important to determine if RA-ILD individuals with short PBL-TL have similarly poor outcomes, as measurement of PBL-TL could be an important tool in guiding treatment decisions.…”

Compound heterozygous mutation of RTEL1 in interstitial lung disease complicated with pneumothorax and emphysema: A case report and literature review

“…In addition, reduced telomere length has also been associated with a shorter time to onset of chronic lung allograft dysfunction (CLAD) 34 . However, a recent study 35 found no difference in the overall post‐LT median survival between the groups with (3.75 years) and without (3.0 years) TRG mutation. Univariate analysis showed the diagnosis of myelodysplasia and a reduced telomere length before LT in TRG mutation carriers were the only factors significantly associated with overall survival, suggesting that LT is hazardous but might be offered to TRG mutation carriers after careful immune‐haematological evaluation.…”