Primary tacrolimus (FK506) therapy and the long-term risk of post-transplant lymphoproliferative disease in pediatric liver transplant recipients

While the overall incidence of post-transplant lymphoproliferative disease (PTLD) in pediatric liver transplant recipients has been reported to be 4-1 1%, the long-term risk of PTLD associated with primary tacrolimus therapy i s unknown. Therefore, in order to determine the incidence and long-term ris k of PTLD, the present study examined 131 pediatric recipients who underwen t liver transplantation (LTx) between October 1989 and December 1991 and re ceived primary tacrolimus therapy. This cohort of children was evaluated ov er an extended time-period (until December 31 1996) with a mean follow-up o f 6.3 yr. Actuarial Kaplan-Meier analysis was utilized to determine the ris k of PTLD over time. The overall incidence of PTLD was 13% (17/131) with an average age of 4.3 +/- 0.75 yr at diagnosis. Pretransplant Epstein-Barr vi rus (EBV) serologies were negative in 82%, positive in 12%, and not availab le in 6% of the patients. The median time to diagnosis of PTLD post-Tx was 11.9 months (mean 16.4 +/- 3.9, range 1.7-63.0 months). Mean tacrolimus dos e and plasma trough level (as evaluated by enzyme-linked immunosorbent assa y [ELISA]) at the time of diagnosis was 0.32 +/- 0.06 mg/kg/day and 1.3 +/- 0.3 ng/mL, respectively. The cumulative long-term risk of PTLD was found t o increase over time: 3% at 6 months, 8% at 1 yr, 12% at 2 yr, 14% at 3 yr, and 15% at 4 and 5 yr. Mortality from PTLD was 12% (two of 17 patients). P rimary tacrolimus use in pediatric LTx has a long-term risk of PTLD approac hing 15%, with the majority of episodes (78%) occurring in the first 2 yr, suggesting that intense EBV surveillance should occur early post-transplant ation.