Adapted treatment of Epstein-Barr virus infection to prevent posttransplant lymphoproliferative disorder after heart transplantation

Am J Transplant. 2014 Apr;14(4):857-66. doi: 10.1111/ajt.12640. Epub 2014 Feb 19.

Abstract

Up to 35% of posttransplant lymphoproliferative disorder (PTLD) cases occur within 1 year of transplantation, and over 50% are associated with Epstein-Barr virus (EBV). EBV primary infection and reactivation are PTLD predictive factors, but there is no consensus for their treatment. We conducted a prospective single-center study on 299 consecutive heart-transplant patients treated with the same immunosuppressive regimen and monitored by repetitive EBV viral-load measurements and endomyocardial biopsies to detect graft rejection. Immunosuppression was tapered on EBV reactivation with EBV viral loads >10(5) copies/mL or primary infection. In the absence of response at 1 month or a viral load >10(6) copies/mL, patients received one rituximab infusion (375 mg/m(2) ). All patients responded to treatment without increased graft rejection. One primary infection case developed a possible PTLD, which completely responded to diminution of immunosuppression, and one patient, whose EBV load was unevaluable, died of respiratory complications secondary to PTLD. Compared with a historical cohort of 820 patients, PTLD incidence was decreased (p = 0.033) by a per-protocol analysis. This is the largest study on EBV primary infection/reactivation treatment, the first using rituximab following solid organ transplantation to prevent PTLD and the first to demonstrate an acceptable tolerability profile in this setting.

Keywords: Epstein-Barr virus; heart transplantation; immunosuppression; posttransplantation lymphoproliferative disease; rituximab.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • DNA, Viral / genetics
  • Epstein-Barr Virus Infections / drug therapy*
  • Epstein-Barr Virus Infections / virology
  • Female
  • Follow-Up Studies
  • Graft Rejection / pathology
  • Graft Rejection / prevention & control*
  • Graft Rejection / virology
  • Heart Transplantation / adverse effects*
  • Herpesvirus 4, Human / genetics
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Lymphoproliferative Disorders / pathology
  • Lymphoproliferative Disorders / prevention & control*
  • Lymphoproliferative Disorders / virology
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Postoperative Complications / pathology
  • Postoperative Complications / prevention & control*
  • Postoperative Complications / virology
  • Prognosis
  • Prospective Studies
  • Risk Factors
  • Viral Load
  • Virus Activation / drug effects
  • Young Adult

Substances

  • DNA, Viral
  • Immunosuppressive Agents