title: Survival in sensitized lung transplant recipients with perioperative desensitization.
abstract: Donor-specific HLA antibodies (DSA) have an adverse effect on short-term and long-term lung transplant outcomes. We implemented a perioperative strategy to treat DSA-positive recipients, leading to equivalent rejection and graft survival outcomes. Pretransplant DSA were identified to HLA-A, B, C, DR and DQ antigens. DSA-positive patients were transplanted if panel reactive antibody (PRA) ≥30% or medically urgent and desensitized with perioperative plasma exchange, intravenous immune globulin, antithymocyte globulin (ATG), and mycophenolic acid (MPA). PRA-positive/DSA-negative recipients received MPA. Unsensitized patients received routine cyclosporine, azathioprine and prednisone without ATG. From 2008-2011, 340 lung-only first transplants were performed: 53 DSA-positive, 93 PRA-positive/DSA-negative and 194 unsensitized. Thirty-day survival was 96 %/99%/96% in the three groups, respectively. One-year graft survival was 89%/88%/86% (p = 0.47). DSA-positive and PRA-positive/DSA-negative patients were less likely to experience any ≥ grade 2 acute rejection (9% and 9% vs. 18% unsensitized p = 0.04). Maximum predicted forced expiratory volume (1 s) (81%/74%/76%, p = NS) and predicted forced vital capacity (81%/77%/78%, respectively, p = NS) were equivalent between groups. With the application of this perioperative treatment protocol, lung transplantation can be safely performed in DSA/PRA-positive patients, with similar outcomes to unsensitized recipients.
authors.affiliation: Laboratory Medicine Program and Department of Medicine, University Health Network, University of Toronto, Toronto, ON, Canada.
authors.forename: K J
authors.initials: KJ
authors.lastname: Tinckam
authors.forename: S
authors.initials: S
authors.lastname: Keshavjee
authors.forename: C
authors.initials: C
authors.lastname: Chaparro
authors.forename: D
authors.initials: D
authors.lastname: Barth
authors.forename: S
authors.initials: S
authors.lastname: Azad
authors.forename: M
authors.initials: M
authors.lastname: Binnie
authors.forename: C W
authors.initials: CW
authors.lastname: Chow
authors.forename: M
authors.initials: M
authors.lastname: de Perrot
authors.forename: A F
authors.initials: AF
authors.lastname: Pierre
authors.forename: T K
authors.initials: TK
authors.lastname: Waddell
authors.forename: K
authors.initials: K
authors.lastname: Yasufuku
authors.forename: M
authors.initials: M
authors.lastname: Cypel
authors.forename: L G
authors.initials: LG
authors.lastname: Singer
mesh_terms: D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D002170:Canada; D015331:Cohort Studies; D003888:Desensitization, Immunologic / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000502:physiology; D006085:Graft Survival / Q000502:physiology*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D008168:Lung / Q000502:physiology* / Q000601:surgery; D016040:Lung Transplantation / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000627:therapeutic use; D019990:Perioperative Care / Q000379:methods*; D010951:Plasma Exchange; D012189:Retrospective Studies; D066027:Transplant Recipients; D016896:Treatment Outcome; D014797:Vital Capacity / Q000502:physiology
chemical_list: D000961:Antilymphocyte Serum; D016756:Immunoglobulins, Intravenous; D009173:Mycophenolic Acid
keywords: alloantibody; clinical research/practice; desensitization; histocompatibility; lung disease; lung transplantation/pulmonology; patient survival; rejection