Abstract 4140154: Highly Sensitized Heart Transplant Recipients Who Have Undergone Pre-Transplant Desensitization Therapies Demonstrate Acceptable Medium-Term Outcomes

Introduction/Research Question: Allosensitization, the presence of circulating anti-HLA antibodies, is a barrier in heart transplantation (HT), restricting the donor pool size, and leading to increased waitlist mortality and rejection risk post-HT. Desensitization therapies can be used to broaden the donor pool in highly sensitized patients, defined as pre-HT calculated panel reactive antibodies (cPRA)≥50%, for antibodies with mean fluorescence intensity (MFI)>10,000. There is paucity of data on longer-term outcomes in such high-immunological risk patients. Methods: Sensitized patients with pre-HT cPRA>50%, who were treated with desensitization and then received HT between 2011-2022 at Cedars-Sinai Medical Center were included. Desensitization therapies included bortezomib, rituximab, tocilizumab, obinutuzumab, intravenous immunoglobulin (IVIG), and plasmapheresis. cPRA, donor-specific antibody (DSA) levels, and post-HT clinical outcomes were assessed up to 5-year follow-up, loss to follow-up, or death. Results: 40 patients were analyzed. 77.5% of patients were female, and all had at least 1 risk factor for sensitization. cPRA decreased from 84.5±13.5% at baseline to 74.1±22.4% after completion of desensitization therapy, prior to transplant (p=0.005). Mean follow-up time post-HT was 4.3±2.9 years. 45.0% of patients had antibody-mediated rejection (AMR), 12.5% had CAV. Overall survival was 94.9%, 92.1%, and 87.5% at 1, 3, and 5 years respectively. All patients except 1 had normal left ventricular function at last follow-up. 72.5% of patients were transplanted in the presence of DSA, and 60.0% underwent post-HT induction with eculizumab in addition to antithymocyte globulin (ATG)/IVIG, while the remaining received ATG/IVIG alone. Among HT recipients with pre-formed DSA, 41.4% had high-level DSA (MFI > 10,000) at time of HT. At 6-12 months post-HT, only 17.2% had high-level DSA, and 41.4% had resolution of DSA. Conclusion: Highly sensitized HT candidates who underwent pre-HT desensitization had comparable survival and CAV rates as compared to the general HT population reported in the literature. However, sensitized patients experienced higher rates of AMR which were not associated with graft dysfunction or mortality.