EARLY SIGNS AND RISK-FACTORS FOR THE INCREASED INCIDENCE OF EPSTEIN-BARR VIRUS-RELATED POSTTRANSPLANT LYMPHOPROLIFERATIVE DISEASES IN PEDIATRIC LIVER-TRANSPLANT RECIPIENTS TREATED WITH TACROLIMUS

Background. Posttransplant lymphoproliferative disease (PTLD) is a lif e-threatening condition the incidence of which in pediatric solid orga n transplantation may be related to the immunosuppressive load. It has been suggested that tacrolimus, a new and potent immunosuppressor, ca uses an increased incidence of this syndrome. Methods. The incidence, early signs, and risk factors for lymphoproliferative disease were rev iewed in a cohort of 89 pediatric liver transplant recipients treated with tacrolimus. Results. Eighteen patients (20%) developed a PTLD-16 concomitant to a primary Epstein-Barr virus (EBV) infection and 2 with previous immunity against EBV. Three additional patients had prelimin ary signs of PTLD concomitant to primary EBV infection, but did not de velop individualized lymphoid masses. Six patients died (6.7% of all t acrolimus-treated patients). Mean tacrolimus blood level during the 3 months preceding EBV infection reached 11.8+/-1.8 ng/ml in PTLD patien ts versus 9.4+/-3.4 ng/ml in non-PTLD patients (0.05<P<0.1). Previous OKT3 or antithymocyte globulin treatment was also significantly associ ated to PTLD. There was no association with age, rejection episodes, s teroid-resistant rejection, prior cytomegalovirus infection, HLA misma tch, living donor or cadaveric organ transplantation, United Network f or Organ Sharing status at the time of orthotopic liver transplant, an d primary or rescue tacrolimus treatment. A significant increase of to tal gamma-globulin level occurred in PTLD patients, and mono/oligoclon al production was significantly associated to PTLD. Conclusion. In EBV -infected pediatric liver transplant recipients, use of OKT3 or antith ymocyte globulin and high tacrolimus blood levels are risk factors for a significant increase in the incidence of PTLD, An increase in total gamma-globulin level and appearance of mono/oligoclonal immunoglobuli n production are the major preliminary signs of the syndrome.