Antibody depletion strategy for the treatment of suspected antibody-mediated rejection in lung transplant recipients: Does it work?

Clin Transplant. 2017 Mar;31(3). doi: 10.1111/ctr.12886. Epub 2017 Feb 1.

Abstract

Background: Donor-specific antibodies (DSAs) after lung transplantation correlate with poor outcomes. The ideal treatment strategy for antibody-mediated rejection AMR is not defined. Our institution implemented an aggressive multimodality protocol for the treatment of suspected AMR.

Methods: Lung transplant recipients with suspected AMR were treated with a standardized protocol of plasma exchange, steroids, bortezomib, rituximab, and intravenous immune globulin. Primary outcome was DSA clearance at 6 months in those alive. Secondary endpoints included preserved allograft function at 6 months, survival at 6 and 12 months and complications due to the protocol.

Results: Sixteen lung transplant recipients with documented DSA and allograft dysfunction were included in the analysis. Of the 16 patients, 11 survived to 6 months. Three of those 11 patients (27%) cleared all DSAs within 6 months of the protocol. Four of the 11 patients (36%) had preserved allograft function at 6 months. Overall 12-month patient survival was 56%. Complications included thrombocytopenia (50%) and abdominal pain or gastrointestinal discomfort (18.7%).

Conclusions: This multimodality protocol resulted in clearance of DSAs and preserved lung function in a minority of lung transplant recipients with suspected AMR surviving to 6 months after therapy. There were significant side effects of the protocol.

Keywords: antibody; therapy; transplants.

MeSH terms

  • Adult
  • Bortezomib / therapeutic use
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Graft Rejection / etiology
  • Graft Rejection / pathology
  • Graft Rejection / prevention & control*
  • Graft Survival / drug effects
  • Graft Survival / immunology*
  • HLA Antigens / immunology
  • Humans
  • Immunoglobulins, Intravenous / administration & dosage
  • Immunosuppressive Agents / therapeutic use*
  • Isoantibodies / immunology*
  • Lung Transplantation / adverse effects*
  • Male
  • Plasmapheresis
  • Postoperative Complications
  • Prognosis
  • Risk Factors
  • Rituximab / therapeutic use
  • Tissue Donors
  • Transplant Recipients*
  • Transplantation, Homologous

Substances

  • HLA Antigens
  • Immunoglobulins, Intravenous
  • Immunosuppressive Agents
  • Isoantibodies
  • Rituximab
  • Bortezomib