(1188) Assessment of Dd-cfDNA Between Stable Single and Double Lung Recipients

PurposePlasma donor-derived cell free DNA (dd-cfDNA) has emerged as a potential biomarker for measuring allograft injury after lung transplant. Differences in donor lung mass between single (S) and double (D) lung transplant recipients (LTRs) may impact the amount of circulating dd-cfDNA detected during injury events. The question remains if dd-cfDNA levels should be consistently adjusted when monitored between stable S and D LTRs. We aimed to compare levels of dd-cfDNA in stable LTRs based on S vs D lung status and time post-transplant.MethodsDd-cfDNA was measured in 3 LTR cohorts: 88 from University Health Science Center San Antonio [(UTHSC-SA) 58 D, 29 S] (AlloSure, CareDx), 20 from Memorial Hermann Hospital [(MHH) 19 D, 1 S] (AlloSure), and 100 from Vall d'Hebron Hospital (83 D, 17 S) (real time-PCR to detect informative INDEL polymorphism for each donor/recipient and digital PCR to quantify dd-cfDNA in recipient plasma). LTRs were excluded if they had any donor specific antibodies post-transplant. Dd-cfDNA samples were defined as stable if negative for acute cellular rejection and pulmonary infection within 1-month pre/post-dd-cfDNA draw. Median dd-cfDNA levels were grouped in 3-month buckets.ResultsA total of 122 dd-cfDNA samples from UTHSC-SA, 60 from MHH, and 286 from Spain were analyzed. Median dd-cfDNA based on S vs D lung status is shown for UTHSC-SA and MHH in Figure 1A, and Spain in Figure 1B. While there were numerical differences in median dd-cfDNA after 12 months post-transplant, these values were influenced by the low number of S LTRs evaluated.ConclusionBased on these data, median dd-cfDNA as measured by 2 different assays did not show appreciable differences between stable S and D lung recipients over time. It remains unclear if all dd-cfDNA levels drawn in S LTRs should be automatically corrected for “threshold” clinical decision making. Future analysis including more S LTRs should be conducted. Evaluation of dd-cfDNA in stable LTRs should rely on assessment of patient-specific trends to guide clinical management. Plasma donor-derived cell free DNA (dd-cfDNA) has emerged as a potential biomarker for measuring allograft injury after lung transplant. Differences in donor lung mass between single (S) and double (D) lung transplant recipients (LTRs) may impact the amount of circulating dd-cfDNA detected during injury events. The question remains if dd-cfDNA levels should be consistently adjusted when monitored between stable S and D LTRs. We aimed to compare levels of dd-cfDNA in stable LTRs based on S vs D lung status and time post-transplant. Dd-cfDNA was measured in 3 LTR cohorts: 88 from University Health Science Center San Antonio [(UTHSC-SA) 58 D, 29 S] (AlloSure, CareDx), 20 from Memorial Hermann Hospital [(MHH) 19 D, 1 S] (AlloSure), and 100 from Vall d'Hebron Hospital (83 D, 17 S) (real time-PCR to detect informative INDEL polymorphism for each donor/recipient and digital PCR to quantify dd-cfDNA in recipient plasma). LTRs were excluded if they had any donor specific antibodies post-transplant. Dd-cfDNA samples were defined as stable if negative for acute cellular rejection and pulmonary infection within 1-month pre/post-dd-cfDNA draw. Median dd-cfDNA levels were grouped in 3-month buckets. A total of 122 dd-cfDNA samples from UTHSC-SA, 60 from MHH, and 286 from Spain were analyzed. Median dd-cfDNA based on S vs D lung status is shown for UTHSC-SA and MHH in Figure 1A, and Spain in Figure 1B. While there were numerical differences in median dd-cfDNA after 12 months post-transplant, these values were influenced by the low number of S LTRs evaluated. Based on these data, median dd-cfDNA as measured by 2 different assays did not show appreciable differences between stable S and D lung recipients over time. It remains unclear if all dd-cfDNA levels drawn in S LTRs should be automatically corrected for “threshold” clinical decision making. Future analysis including more S LTRs should be conducted. Evaluation of dd-cfDNA in stable LTRs should rely on assessment of patient-specific trends to guide clinical management.