Splenic Irradiation for the Treatment of Severe Antibody-Mediated Rejection

Am J Transplant. 2016 Oct;16(10):3041-3045. doi: 10.1111/ajt.13882. Epub 2016 Jun 27.

Abstract

Patients requiring desensitization prior to renal transplantation are at risk for developing severe antibody-mediated rejection (AMR) refractory to treatment with plasmapheresis and intravenous immunoglobulin (PP/IVIg). We have previously reported success at graft salvage, long-term graft survival and protection against transplant glomerulopathy with the use of eculizumab and splenectomy in addition to PP/IVIg. Splenectomy may be an important component of this combination therapy and is itself associated with a marked reduction in donor-specific antibody (DSA) production. However, splenectomy represents a major operation, and some patients with severe AMR have comorbid conditions that substantially increase their risk of complications during and after surgery. In an effort to spare recipients the morbidity of a second operation, we used splenic irradiation in lieu of splenectomy in two incompatible live donor kidney transplant recipients with severe AMR in addition to PP/IVIg, rituximab and eculizumab. This novel approach to the treatment of severe AMR was associated with allograft salvage, excellent graft function and no short- or medium-term adverse effects of the radiation therapy. One-year surveillance biopsies did not show transplant glomerulopathy (tg) on light microscopy, but microcirculation inflammation and tg were present on electron microscopy.

Keywords: alloantibody; clinical research/practice; desensitization; histocompatibility; immunosuppression/immune modulation; intravenous immunoglobulin/IVIG; kidney transplantation/nephrology; plasmapheresis/plasma exchange; rejection: antibody-mediated (ABMR).

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Desensitization, Immunologic
  • Female
  • Gamma Rays
  • Glomerular Filtration Rate
  • Graft Rejection / etiology
  • Graft Rejection / radiotherapy*
  • Graft Survival / immunology
  • Graft Survival / radiation effects*
  • Histocompatibility Testing
  • Humans
  • Immunoglobulins, Intravenous / administration & dosage
  • Immunosuppressive Agents / therapeutic use
  • Isoantibodies / adverse effects*
  • Kidney Failure, Chronic / surgery*
  • Kidney Function Tests
  • Kidney Transplantation / adverse effects*
  • Middle Aged
  • Plasmapheresis
  • Postoperative Complications
  • Prognosis
  • Spleen / immunology
  • Spleen / pathology
  • Spleen / radiation effects*
  • Splenectomy / adverse effects*

Substances

  • Immunoglobulins, Intravenous
  • Immunosuppressive Agents
  • Isoantibodies