Antibody Mediated Rejection in Pediatric Heart Transplant Recipients

Abstract

<h3>Purpose</h3> Pediatric heart transplant recipients who experience antibody mediated rejection (AMR) are at increased risk for poor graft outcomes. We report the incidence, treatment, and outcomes of AMR at our center. <h3>Methods</h3> Transplant recipients treated for AMR between 2010 and 2021 were identified. We reviewed AMR episodes, therapies, and graft outcomes. <h3>Results</h3> Of 183 transplants performed, 25 patients experienced 37 episodes of AMR, representing an incidence of 14%. 89% of patients were transplanted for congenital heart disease, 40% were sensitized pre-transplant, and 28% had a crossmatch positive transplant. In 33 of 37 episodes (89%), there was both strong DSA (>4,000 mfi) and findings of pathologic AMR (pAMR) on endomyocardial biopsy. Two patients had DSA <4,000 mfi with pAMR findings, one had strong DSA but died prior to biopsy, and one had strong DSA with negative pAMR but with graft dysfunction without other explanation. The first rejection episode occurred at a median of 50 days (IQR 17-635 days) from transplant. 19% of episodes were with hemodynamic compromise and 36% of patients had recurrence of AMR. Biopsy findings showed pAMR 0 in 3%, pAMR 1 (H+) in 47%, pAMR 1 (I+) in 17%, and pAMR 2 in 33%. 75% had mixed ACR/pAMR. Therapy included anti-thymocyte globulin in 13% (predominately for rejection with hemodynamic compromise), methylprednisolone in 92%, IVIG in 97%, bortezomib in 78%, rituximab in 73%, plasmapheresis in 35%, and eculizumab in 22%. A combination of 2 or greater antibody directed therapies was used in 89% of episodes and 3 or greater therapies in 70%. IVIG/bortezomib/rituximab was the most common therapy combination, used in 32% of episodes. pAMR findings resolved in 64% at 3 months and 79% at 1 year. During a median follow up of 4 years (IQR 1-6 years) from first AMR, there were 8 graft losses (2 retransplants and 6 deaths). The median time from AMR to graft loss was 7 months (IQR 2 months - 4.5 years). 20% of patients developed cardiac allograft vasculopathy at a median duration of 4.8 years (IQR 4-7) from AMR and 8 years (IQR 5-9) from transplant. Retransplant free survival from first AMR was 83% at 1 year, 76% at 3 years, and 63% at 5 years. <h3>Conclusion</h3> AMR occurred early post-transplant and recurrence was common. Treatment strategies varied, however combination therapy was nearly always employed. Despite relatively early graft loss after first AMR, AMR can be treated to prolong graft survival.