*Purpose: Pre-transplant allosensitization remains a significant barrier to organ allocation and a paucity of evidence exists to demonstrate the efficacy and safety of perioperative desensitization in orthotopic heart transplantation (OHT).

*Methods: This single-center, retrospective analysis included OHT recipients from 2010-2018. Virtual crossmatch (VXM)-negative patients received standard immunosuppression with high-dose steroids or induction with alemtuzumab. Perioperative desensitization for VXM-positive patients included plasmapheresis, intravenous immunoglobulin, and antithymocyte globulin. The primary endpoint was freedom from acute rejection at 12 months. Secondary endpoints included infectious complications, freedom from severe (i.e., grade ≥ 2) acute cellular rejection (ACR) or antibody-mediated rejection (AMR), graft survival, concomitant maintenance immunosuppression, and changes in renal function at 12 months.

*Results: Of 84 patients included, 44 received standard immunosuppression, 33 received alemtuzumab, and 7 received perioperative desensitization. Baseline characteristics were similar between groups, aside from more African Americans receiving desensitization. No significant differences in ACR or AMR were observed at 12 months between desensitized patients and those receiving standard immunosuppression or alemtuzumab (Figures 1 and 2). The median time to rejection was 32 days (11.5-69) in the standard group, 104.5 days (45.8-276) in the alemtuzumab group, and 46.5 days (10-83) in the desensitized group (p=0.04 for the comparison of standard to alemtuzumab). The incidence of opportunistic infections was similar in the three groups (Figure 3). Recipients receiving desensitization were more likely to receive higher doses of mycophenolate mofetil and prednisone at months 1 and 3, as well as higher median tacrolimus trough concentrations at month 6 compared to patients receiving alemtuzumab (8.9 ng/mL vs. 13.9 ng/mL, p=0.05). The latter was not associated with worsened glomerular filtration rate (GFR) in the desensitized group (Figure 4).

*Conclusions: The present study suggests that a desensitization strategy may permit heart transplantation in allosensitized recipients without excess acute rejection. Despite higher levels of maintenance immunosuppression in those receiving desensitization, there was not an increased risk of opportunistic infection or a worsening of renal indices.

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