title: Splenic Irradiation for the Treatment of Severe Antibody-Mediated Rejection.
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.
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: B J
authors.initials: BJ
authors.lastname: Orandi
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: B E
authors.initials: BE
authors.lastname: Lonze
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: A
authors.initials: A
authors.lastname: Jackson
authors.affiliation: Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: S
authors.initials: S
authors.lastname: Terezakis
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: E S
authors.initials: ES
authors.lastname: Kraus
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: N
authors.initials: N
authors.lastname: Alachkar
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: S M
authors.initials: SM
authors.lastname: Bagnasco
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: D L
authors.initials: DL
authors.lastname: Segev
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: J B
authors.initials: JB
authors.lastname: Orens
authors.affiliation: New York University (NYU) Langone Transplant Institute, New York, NY.
authors.forename: R A
authors.initials: RA
authors.lastname: Montgomery
mesh_terms: D000328:Adult; D003888:Desensitization, Immunologic; D005260:Female; D005720:Gamma Rays; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000209:etiology / Q000532:radiotherapy*; D006085:Graft Survival / Q000276:immunology / Q000528:radiation effects*; D006650:Histocompatibility Testing; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007518:Isoantibodies / Q000009:adverse effects*; D007676:Kidney Failure, Chronic / Q000601:surgery*; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D008875:Middle Aged; D010956:Plasmapheresis; D011183:Postoperative Complications; D011379:Prognosis; D013154:Spleen / Q000276:immunology / Q000473:pathology / Q000528:radiation effects*; D013156:Splenectomy / Q000009:adverse effects*
chemical_list: D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D007518:Isoantibodies
keywords: alloantibody; clinical research/practice; desensitization; histocompatibility; immunosuppression/immune modulation; intravenous immunoglobulin/IVIG; kidney transplantation/nephrology; plasmapheresis/plasma exchange; rejection: antibody-mediated (ABMR)