Immunoadsorption for Acute Symptomatic Antibody-Mediated Rejection after Heart Transplantation

Abstract

Purpose Antibody-mediated rejection (AMR) after heart transplantation (HTX) is associated with adverse outcomes . A standardized therapeutic regimen has not yet been defined. Immunoadsorption (IA) has shown promising results in AMR after kidney transplantation . We present our results with IA for acute symptomatic AMR after HTX. Methods This retrospective single-center study included all consecutive patients with proven and treated symptomatic AMR between 2006 and 2016. Survival from AMR, incidence of cardiac allograft vasculopathy (CAV) as well as donor specific anti-HLA-antibody (DSA) cumulative mean fluorescence intensity (MFI) assessed by LUMINEX single antigen bead assay are described. Results 22 patients were designated to undergo extracorporeal antibody removal for symptomatic AMR and received IA (n=18, 81,8 %) or plasmapheresis (PP; n=1, 4,5 %). One patient was switched to IA after one initial PP. In two patients IA/PP was not initiated due to unfavorable prognosis. Concomitant therapy was methylprednisolone (100 %), IVIg (9 %) and rituximab (4,5 %). AMR occurred after a median of 5.65 months (IQR 0.43-21.4) from HTX. Overall survival after a median follow up of 4.85 years from AMR diagnosis was 63.6 %. Mortality 30 days, 1 year and 5 years after AMR onset was 27.3 %, 31.8 % and 31.8 %. 4 patients (18.2 %) developed severe CAV (ISHLT grade ≥ 2) after a median time of 30.5 months after AMR onset. 21 patients had positive DSA at the time of AMR diagnosis (HLA I only: 13.6 %, HLA II only: 50 %, HLA I+II: 31.8%). Conclusion Despite high early mortality, long-term outcome of patients surviving the acute phase is encouraging, however we observed an increased burden of CAV. Due to the oftentimes fulminant clinical course, rapid diagnosis and therapy, facilitated by close interdisciplinary cooperation of intensivists , cardiac surgeons and nephrologists is crucial. Next steps include a detailed characterization of DSAs over the treatment period as well as endomyocardial biopsy specimens of patients with AMR.