Clinical Outcomes of Perioperative Desensitization in Orthotopic Heart Transplant Recipients

Purpose Transplantation of sensitized recipients is associated with suboptimal post-transplant outcomes. This study assessed the effects of a perioperative desensitization strategy in virtual crossmatch (VXM)-positive orthotopic heart transplant (OHT) recipients compared to a historical cohort of VXM-negative OHT recipients. Methods This single-center, retrospective study included OHT recipients from 2010-2018. VXM-positive patients received perioperative plasmapheresis, intravenous immunoglobulin (IVIg), and antithymocyte globulin (rATG). VXM-negative historical controls received either high-dose steroids or alemtuzumab induction. Maintenance immunosuppression consisted of tacrolimus, mycophenolate, and a steroid taper. The primary endpoint was graft survival at 12 months. Secondary endpoints included freedom from acute rejection and freedom from severe (i.e., grade ≥ 2) acute cellular rejection or antibody-mediated rejection at 12 months. Results Of 91 patients included, 7 received desensitization. Baseline demographics, disease etiology, and comorbid conditions were similar between groups. VXM-positive recipients received a median of 5.1 (4.8-5.3) mg/kg of rATG, 0.9 (0-1.2) g/kg of IVIg, and 6 (3-7) plasmapheresis sessions. Maintenance immunosuppression was similar at all time points. There was one graft loss, which occurred in the VXM-negative cohort at 70 days post-OHT. The median time to rejection was 44.5 (16.5-93.5) days in the VXM-negative group versus 46.5 (10-83) days in the VXM-positive group (p=0.76). There were no differences in any other rejection outcomes. Six VXM-positive recipients cleared donor-specific antibodies (DSA) by day 21 and all cleared DSA by day 60 (Figure 1). Conclusion These data suggest that transplantation of VXM-positive OHT recipients receiving perioperative desensitization is feasible without excess graft loss or acute rejection at 12 months. The rapid clearance and lack of DSA recurrence is promising for long-term outcomes.