Adapted Management of EBV Reactivation After Solid Organ Transplantation: An Effective Prevention of Post Transplantation Lymphoproliferative Disorders (PTLD). Results of the Largest Prospective Study on 251 Patients

PTLD represent a rare but aggressive graft complication. Patients who have received a solid organ transplantation have a 20 to 120 fold higher incidence of non-Hodgkin's lymphoma. EBV reactivation represents a major predictive factor for PTLD, especially during the first year after transplantation, but there is no consensual attitude in this situation

We conducted a monocentric prospective study in the Hospital of Pitie Salpêtriere, Paris, France, on all new heart transplanted patients. EBV viral load (EVL) on whole blood samples was systematically followed and confirmed reactivations were treated depending on viral load.

All heart transplanted patients who had at least one EVL between January 2004 and December 2008 were included. Immunosuppression consisted on anti-lymphocyte sera, ciclosporin, mycophenolate-mofetyl (MM) and prednisone. Twelve to 15 blood samples per year were analysed. If the EVL was more than 10⁵ copies/ml, a CT scan or a PET-san was performed in order to detect any PTLD and patients were treated by diminution of the immunosupression (DIS), mainly by MM arrest. One injection of Rituximab (R) (375 mg/m²) was used in case of failure and/or if EVL was over 10⁶ copies/ml.

A total of 251 patients were included, 59 femals/192 men, of a median age of 50 years [16-72]. All but 6 were EBV positive before the graft. Reactivations were detected in 29 cases (11,55%) and treated by DIS only in 20 cases, DIS followed by R in 5 and directly by DIS and R in 4. All EBV negative patients developed a primoinfection in the first year, 2 with an EVL over 10⁵, one presented non documented hepatic lesions which disappeared after DIS. All EBV reactivations were controlled, with a relapse in only one case (reactivations treated the first time by DIS, 10 months later by DIS and R and 6 months later by DIS). With a median follow-up of 1118 days [53-2100] only one PTLD has been diagnosed (in a patient lost to follow up and taken in charge in an other unit) and 24 patients died (9,5%). Analyse of DIS +/− R on graft rejection and potential link between CMV reactivation and EBV reactivation will be presented at the ASH. From 1987 to December 2003, 24 (1,8/year) PTLD have been treated in the same unit (18 EBV positive, 5 negative, 1 unknown), of which 13 were early PTLD (all EBV positive) diagnosed within one year post transplantation.

EBV reactivation after organ transplantation can be managed by diminution of immunosupression and/or rituximab, depending on viral load, without serious complication. This adapted management seems to decrease dramatically the incidence of EBV positive PTLD.

Choquet:ROCHE: Consultancy. Leblond:ROCHE: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MUNDIPHARMA: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CELGENE: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees.