Treatment of ANTI-HLA Donor-Specific Antibodies and Antibody-Mediated Rejection in Heart Transplantation: A Single-Center 3-Year Experience

Objectives: The presence of anti-HLA donor specific antibodies (DSA) after heart transplantation is associated with antibody-mediated rejection (AMR) and poor graft survival. Aim of this study was to present the results of our treatment protocol of DSA in heart transplantation.

Methods: Since late 2016, at our institution, heart-transplanted patients with DSA but without graft dysfunction (Group 1) were treated with IgA- and IgM-enriched intravenous immunoglobulins (IgGAM) only (first infusion: 2 g/kg, then 0.5 g/kg once every 4 weeks for a maximum of 6 months). Patients with DSA and graft dysfunction (Group 2, clinical AMR) were treated with additional 5 sessions of plasmapheresis (PE) before IgGAM and a single dose of anti-CD20 antibody (Rituximab, 375 mg/m²) after the first IgGAM infusion. Highly allosensitized (PRA>50%) patients showing preformed DSA (pfDSA), i.e., a positive virtual crossmatch (Group 3), were treated with an intraoperative single dose of the IL-6 receptor antibody tocilizumab (10 mg/kg), in addition to 5 sessions of PE, IgGAM infusions and a single rituximab dose, as aforementioned.

Result: Among the 93 patients transplanted between 10/2016 and 09/2020, four (4%) patients formed Group 1, 11 (12%) patients formed Group 2, and 14 (15%) patients formed Group 3.

Group 1 patients developed de novo DSA 31, 145, 28, and 9 days after transplantation, were treated with IgGAM, which cleared DSA in all patients, were alive and did not show any episode of biopsy-confirmed rejection (ISHLT Grade R > 1) at the end of follow-up.

Group 2 patients developed de novo DSA at a median of 204 days after transplantation and showed graft dysfunction requiring ECMO support in five cases. Five (45%) patients died in-hospital. Among the 6 surviving patients, DSA were cleared in three patients.

Group 3 patients showed pfDSA with >50% pretransplant PRA. Posttransplant, patients did not show any antibody-mediated severe primary graft dysfunction, but one patient died in hospital of pneumonia. pfDSA were cleared in eight (57%) patients. At follow-up, all discharged patients survived, and three patients showed at least one episode of ISHLT Grade R > 1 rejection or of minimal AMR (pAMR 1+).

Conclusion: In heart transplantation, clinical AMR showed a dismal prognosis, despite treatment. Early diagnosis and preemptive treatment of DSA should be pursued. Transplantation across positive crossmatch barriers can be feasible and safe.

Publication History

Article published online:
19 February 2021