Adapted Treatment of Epstein–Barr Virus Infection to Prevent Posttransplant Lymphoproliferative Disorder After Heart Transplantation

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 >105 copies/mL or primary infection. In the absence of response at 1 month or a viral load >106 copies/mL, patients received one rituximab infusion (375 mg/m2). 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.