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Purpose Highly sensitized recipients remain a challenge in lung transplantation. There are no standardized protocols among lung transplant centers to guide management of these patients. Some centers choose not to transplant highly sensitized patients due to the risk of graft dysfunction and death. We describe our center's experience and outcomes managing lung transplant recipients with positive flow-cytometric prospective cross matches (FXM). Methods We retrospectively analyzed patients who underwent lung transplantation with positive FXM from August 2015 to November 2019. Outcomes included overall length of stay, 1-year survival, graft function at one year, and incidence of antibody mediated rejection (AMR) and CLAD (BOS). Results There were 11 patients with FXM (6 females, 5 males; 6 with restrictive lung disease, 3 with obstructive lung disease, 1 with cystic fibrosis, and 1 with pulmonary vascular disease). 7 (63%) had concomitant positive virtual cross matches. 10 (91%) were managed with high-dose IVIg alone immediately post-op. 3 patients additionally received intra and/or post-op plasma exchange, rituximab and/or bortezimab. Median length of hospital stay was 50 days. Median length of follow up is 30 months (range 11-63 months). KM estimate of one-year survival was 90%. Clinical episodes of AMR requiring treatment occurred in 1 (9%) patient at 3 years post-transplant. DSA cleared in 8 patients (73%). Infections occurred in 5 patients (45%). None were life threatening. CLAD grade ≥ 1 occurred in only 2 patients (18%), one at 1.5 years and the other 3 years post-transplant. FEV1 at one year was >89% of personal best in all patients. Conclusion Successful lung transplantation of highly sensitized recipients is feasible. Using our center's approach results in longer hospital stay but excellent one-year outcomes. Further study is needed to identify patients at risk for graft dysfunction and death due to AMR who benefit from early aggressive treatment, and to avoid unnecessary treatment in lower risk patients.

SESSION TITLE: Transplantation Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Chronic lung allograft dysfunction (CLAD) remains the leading cause of long-term mortality after lung transplantation (LTX) with no proven therapeutic strategies except re-transplantation Anecdotal reports suggest a role for the lymphocyte depleting agent, Alemtuzumab (AL), an anti-CD52 monoclonal antibody We reviewed our experience with AL for the treatment of refractory CLAD METHODS: Eight consecutive LTX recipients were identified AL was given as a single subcutaneous dose of 30 mg Cell-cycle inhibitor therapy was held and valganciclovir and azole prophylaxis were given for at least 6 months after AL treatment The slope of FEV1 3 months before and after AL were compared Complications of AL therapy including infections and survival were assessed RESULTS: The cohort consisted of 5 males and 3 females with a median age at time of AL administration of 66 y (range: 50-72) Time post-transplant was 2 43 y (range: 1 4-5 4) Pre-transplant diagnoses were COPD (n=3), and 1 each of CF, bronchiectasis (immotile cilia syndrome), IPF, PVOD and IPAH All subjects were bilateral recipients and 1 was post-left pneumonectomy early after transplant All had a predominantly obstructive CLAD phenotype, stages 4 (N=2), 3 (N=4), 2 (N=1) and 1 (N=1) with rapid loss of lung function The median slope of decline in FEV1 in the 3 months prior to AL was -336ml/m (range: -39 to -552) compared with +24 ml/m (range: -171 to +48) during the 3 months post AL administration (P = 0 016) No acute reactions to AL treatment were observed Clinically symptomatic infections occurred in 4 patients following AL Community acquired respiratory viral infections were observed in 2 (parainfluenza and coronavirus on 2 separate occasions in 1 patient and rhinovirus in another) Pseudomonas tracheobronchitis developed in 1 These infections were considered mild-moderate One subject developed new parenchymal opacities with isolation of Rasamsonia argillacea and Mycobacterium fortuitum Two patients died due to progressive CLAD 3 and 6 months after AL The other six are alive at a median follow-up time of 12 months (range: 7 – 20) Kaplan-Meier survival estimate at one year was 75% At last follow-up, CLAD stages among survivors was 4 (N=1), 3 (N=4) and 2 (N=1) CONCLUSIONS: AL therapy was associated with a significant attenuation in lung function decline in lung transplant recipients with rapidly progressive CLAD Treatment was generally well tolerated with few serious infection complications CLINICAL IMPLICATIONS: AL should be considered for rapidly progressive CLAD Randomized controlled trials are required to establish efficacy and safety DISCLOSURES: No relevant relationships by Reda Girgis, source=Web Response No relevant relationships by Ryan Hadley, source=Web Response no disclosure submitted for Anupam Kumar;No relevant relationships by Cameron Lawson, source=Web Response no disclosure on file for Marzia Leacche;No relevant relationships by Jennifer McDermott, source=Web Response no disclosure on file for Edward Murphy;No relevant relationships by Gayathri Sathiyamoorthy, source=Web Response