Surveillance Donor-derived Cell-free DNA Allows for the Safe Reduction in Protocol Transbronchial Biopsies After Lung Transplantation.

Background: Protocol transbronchial biopsies (TBBx) are standard of practice (SOP) in most lung transplantation (LT) centers for surveillance of acute cellular rejection. In the context of higher LT center volumes, our program experienced increasing difficulty scheduling SOP protocol TBBx at months 1, 3, 6, 9, and 12 post-LT. As part of a Quality Assurance Performance Improvement initiative, we designed this prospective study to assess the efficacy and safety of adopting donor-derived cell-free DNA (dd-cfDNA) surveillance in lieu of protocol TBBx during the initial year after LT at our center. Methods: Enrolled LT patients with "low-risk" dd-cfDNA (<1.0%) had their 9-mo (9M) protocol TBBx omitted, whereas the 9M protocol TBBx was performed when dd-cfDNA indicated a "high-risk" result (≥1.0%) or for clinical indications. All patients received a protocol TBBx at 12M to assure detection of subclinical acute cellular rejection. We also assessed clinical data from the first year, including change in forced expiratory volume-1 s, donor-specific antibodies, and performed a health economic analysis. Results: Among 78 enrolled LT patients, 24 were "high risk" (8 with omitted 9M protocol TBBx because of clinical contraindications), and 54 "low risk" (41 with omitted 9M protocol TBBx) by dd-cfDNA. Of the patients with omitted 9M protocol TBBx, 10.2% (5/49) showed rejection at 12 mo compared with 20.7% (6/29), at either the 9M or 12M protocol TBBx. Median change in forced expiratory volume-1 s (baseline-12M) was similar between "high-risk" and "low-risk" cohorts (P = 0.592) and for "omitted" versus "performed" 9M protocol TBBx cohorts (P = 0.271). Conclusions: Our Quality Assurance Performance Improvement study offered assurances for safety, efficacy, and reduction in healthcare costs when implementing SOP dd-cfDNA surveillance, with a >75% reduction in 9M protocol TBBx procedures among patients who were "low risk" by dd-cfDNA.