Xenotransplantation Immunosuppression Protocol

The goal was to replicate the laboratory protocols we had used successfully with a nonhuman primate model, while balancing the patient’s preoperative leukopenia (white-cell count, 2200 to 3200 per microliter) and baseline thrombocytopenia (platelet count, 90,000 to 111,000 per microliter) before induction (Fig. S1 and Table S2).^{12 (link),13} Rituximab and antithymocyte globulin were used for B-cell and T-cell depletion, respectively, and complement C1 esterase inhibitor (Berinert, CSL Behring) was used for complement inhibition. Humanized monoclonal antibody (KPL-404, Kiniksa Pharmaceuticals), used to block CD40 costimulation, was administered through repeated single dosing. A pulse dose of methylprednisolone (1000 mg on the day of xenotransplantation) was also administered.^{12 (link)} Maintenance immunosuppression included mycophenolate mofetil, KPL-404, and a rapid taper of methylprednisolone (from 125 mg daily to 30 mg daily).