Efficacy and Safety of Desensitization Therapy in Pediatric Heart Transplant Candidates

Abstract

<h3>Purpose</h3> Allosensitization to human leukocyte antigen (HLA) in pediatric heart transplant candidates is associated with higher waitlist, post-transplantation mortality and antibody mediated rejection. As limited safety/efficacy data exist on pre-transplant desensitization regimen, we reviewed our institution's experience. <h3>Methods</h3> We reviewed the medical records of 12 highly sensitized (average cPRA = 68%) pediatric heart transplant candidates who underwent desensitization therapy at the University of Virginia Hospital between 2014 and 2020. The following data were collected: individual immunosuppression regimen, pre and post desensitization levels of antibody burden, documented side effects, and incidence of antibody mediated rejection. <h3>Results</h3> The majority of patients received an oral immunosuppressive regimen of Prednisone (0.3 mg/kg/day to max dose of 12.5 mg) and an antimetabolite (Cellcept 60 mg/kg/dose q12 up to 1,000 mg q12 or Imuran 1-2 mg/kg/day) followed by a single infusion of Rituximab (375 mg/m2) and monthly intravenous immunoglobulin (IVIG 2 g/kg) infusions; plasmapheresis was used in one patient and Bortezomib was used in two. cPRA decreased by an average of nearly 20% after an average of 17.5 weeks (Table 1). HLA I antibodies were more susceptible to desensitization than HLA II antibodies (60% vs 36% average antibody reduction, respectively). Immunosuppression medications were well tolerated with only one patient requiring Rituximab discontinuation due to hypotension, tachycardia and respiratory distress. There were no cases of antibody mediated rejection in those patients who underwent transplantation. <h3>Conclusion</h3> In our cohort, B-cell/ antibody targeted therapies were safe and effective in improving allosensitization and allowing for successful transplantation, though HLA II antibodies were more resistant to therapy. Larger scale studies are needed.