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.

No conflict of interest has been declared by the author(s).

Publication History

Article published online:
19 February 2021