Abstract Rationale We have previously shown that short telomere pulmonary fibrosis lung transplant recipients (STLPF-LTRs) have impaired immunity to cytomegalovirus (CMV) and are at increased risk of developing CMV viremia post- lung transplant. Patients with STL are also prone to cytopenias and tend to have poor tolerance to the standard CMV prophylaxis medication Valganciclovir post-transplant. We investigated the use of Letermovir as alternative CMV prophylaxis and the incidence of CMV viremia in a retrospective cohort of 18 PF-LTRs. Methods Post-transplant data were extracted on a retrospective cohort of 18 PF-LTRs: 14 STLPF-LTRs and 4 LTPF-LTRs (median age 55 and 65 respectively). Lymphocyte and granulocyte TL were measured using flow cytometry and fluorescence in-situ hybridization (flowFISH). Genetic assessment was done using Whole Genome Sequencing or a targeted sequence panel. Results A small cohort of 18 PF-LTRs: 14 STLPF-LTRs and 4 LTPF-LTRs who underwent double lung transplant between 2018 and 2024 were identified retrospectively at our institution. In the STLPF-LTR cohort, FlowFISH revealed lymphocyte TL at or below the 1st percentile in 50% (7/14) and below 10th percentile 50% (7/14). Granulocytes were measured in 13/14 with 62% (8/13) at or below the 1st percentile and 5/13 (38%) below the 10th percentile. 12/14 (86%) underwent genetic characterization for the telomere maintenance genes with 10/14 (71%) having a rare gene variant: 5 in RTEL1, 2 in TERT and 3 in PARN. The 4 LTPF-LTRs did not undergo genetic characterization. In the STLPF-LTR cohort, 4/14 (28%) were CMV mismatches (donor positive, recipient negative), and 10/14 (71%) were recipient positive. 75% (3/4) of the LTPF-LTRs were CMV mismatches and 1/4 (25%) was recipient positive. Our entire cohort of 18 PF- LTRs received Letermovir immediately post-transplant as alternative CMV prophylaxis with length of prophylaxis ranging between 6-12 months. There was one patient (1/18; 7%) that developed primary CMV infection 15 days post-transplant while on Letermovir. This patient had TL 1st percentile in both lymphocytes and granulocytes and a telomere gene variant in RTEL1. 5/14 (36%) STLPF-LTRs developed CMV viremia after discontinuation of Letermovir prophylaxis with median time to primary CMV infection being 369 days. Of the LTPF-LTRs 75% (3/4), which were all CMV mismatches, developed CMV viremia with median time to primary infection being 397 days. Conclusions The use of Letermovir for post-lung transplant primary CMV prophylaxis is well-tolerated overall and is an effective alternative to Valganciclovir in STLPF-LTRs in preventing CMV viremia and complications. This abstract is funded by: NHLBI R01 HL166265, the Raman Family Lung Transplantation Fund
Hannan et al. (Fri,) studied this question.