(474) - Late Antibody-Mediated Rejection Due To De-Novo Donor-Specific Anti-HLA Antibodies in Heart Transplant Recipients: A Cohort of 20 Consecutive Patients

Abstract

PurposeWhereas early antibody-mediated rejections (AMR) in sensitized patients are well described, data are scarce concerning late AMR due to de novo donor-specific anti-HLA antibodies (DSA) in heart transplant recipients.MethodsWe performed a retrospective observational cohort study in a high volume heart transplantation center. We included all patients treated for late symptomatic AMR due to de novo DSA from November 2006 to February 2013. We realized retrospective blinded reinterpretation of EMB (including EMB before and after treated AMR).ResultsLate AMR due to de novo DSA was diagnosed in 20 patients. Prevalence was estimated to 2 %. All patients but one had evidence of allograft dysfunction (cardiogenic shocks: n = 6). De novo DSA were identified in all patients (MFI range: 312 to 49395). Typical histological patterns of AMR were found in 18 patients (90 %). Despite aggressive immunosuppressive therapies (IV methylprednisolone: 100 % of patients, IVIg: 90 %, plasmapheresis: 85 %, Rituximab: 45 %), the prognosis remained poor: survival was 80 % at 1 month, 60 % at 3 months and 50 % at 1 year (see figure). Median survival was 0.96 years. Among patients alive at 3 months (n = 12), one third had evidence of histological AMR relapse during follow-up. Two patients developed fulminant cardiac allograft vasculopathy (CAV) in the month following AMR. Interestingly, signs of microvascular inflammation were observed on previous BEM for 13 patients (65%).Conclusion PurposeWhereas early antibody-mediated rejections (AMR) in sensitized patients are well described, data are scarce concerning late AMR due to de novo donor-specific anti-HLA antibodies (DSA) in heart transplant recipients. Whereas early antibody-mediated rejections (AMR) in sensitized patients are well described, data are scarce concerning late AMR due to de novo donor-specific anti-HLA antibodies (DSA) in heart transplant recipients. MethodsWe performed a retrospective observational cohort study in a high volume heart transplantation center. We included all patients treated for late symptomatic AMR due to de novo DSA from November 2006 to February 2013. We realized retrospective blinded reinterpretation of EMB (including EMB before and after treated AMR). We performed a retrospective observational cohort study in a high volume heart transplantation center. We included all patients treated for late symptomatic AMR due to de novo DSA from November 2006 to February 2013. We realized retrospective blinded reinterpretation of EMB (including EMB before and after treated AMR). ResultsLate AMR due to de novo DSA was diagnosed in 20 patients. Prevalence was estimated to 2 %. All patients but one had evidence of allograft dysfunction (cardiogenic shocks: n = 6). De novo DSA were identified in all patients (MFI range: 312 to 49395). Typical histological patterns of AMR were found in 18 patients (90 %). Despite aggressive immunosuppressive therapies (IV methylprednisolone: 100 % of patients, IVIg: 90 %, plasmapheresis: 85 %, Rituximab: 45 %), the prognosis remained poor: survival was 80 % at 1 month, 60 % at 3 months and 50 % at 1 year (see figure). Median survival was 0.96 years. Among patients alive at 3 months (n = 12), one third had evidence of histological AMR relapse during follow-up. Two patients developed fulminant cardiac allograft vasculopathy (CAV) in the month following AMR. Interestingly, signs of microvascular inflammation were observed on previous BEM for 13 patients (65%). Late AMR due to de novo DSA was diagnosed in 20 patients. Prevalence was estimated to 2 %. All patients but one had evidence of allograft dysfunction (cardiogenic shocks: n = 6). De novo DSA were identified in all patients (MFI range: 312 to 49395). Typical histological patterns of AMR were found in 18 patients (90 %). Despite aggressive immunosuppressive therapies (IV methylprednisolone: 100 % of patients, IVIg: 90 %, plasmapheresis: 85 %, Rituximab: 45 %), the prognosis remained poor: survival was 80 % at 1 month, 60 % at 3 months and 50 % at 1 year (see figure). Median survival was 0.96 years. Among patients alive at 3 months (n = 12), one third had evidence of histological AMR relapse during follow-up. Two patients developed fulminant cardiac allograft vasculopathy (CAV) in the month following AMR. Interestingly, signs of microvascular inflammation were observed on previous BEM for 13 patients (65%). Conclusion