409 We previously reported a 10% incidence of lymphoproliferative disease (LPD) in pediatric patients receiving first liver grafts and primarily immunosuppressed with tacrolimus (tac). To decrease the incidence of LPD we developed a protocol utilizing pre-emptive ganciclovir (ganc) in high risk recipients (i.e. donor (D) +, recipient (R) -, combined with serial monitoring of peripherel blood for Epstein Barr Virus (EBV) by PCR. METHODS: Consecutive pediatric recipients of a first liver graft were immunosuppressed with oral tac (both induction and maintenance), and low dose prednisone. Targeted tac levels were 10-12 ng/ml mo 0-1, 8-10 ng/ml mo 1-2, and 5-10 ng/ml thereafter. EBV serologies were obtained at the time of OLT in recipients and donors. Recipients were divided into groups: Group 1, High Risk (D+ R-), and Group 2, Low Risk (D+ R+; D-R-; D-R+). In Gp 1 (HR), all pts received a minimum of 100 day of IV ganc (6-10 mg/kg/day) while in Gp 2 (LR) pts received IV ganc during their initial hospitalization and then converted to oral acyclovir 40 mg/kg/day at discharge. Semi-quantitative EBV PCR determinations were made at 1-2 mo intervals. PCR results were categorized as follows: low positive (5-10 viral DNA copies), ⊕ (10-1000 copies), and ⊕⊕ (> 1000 copies). In both groups, pts with an ⊕ EBV PCR, or PCR⊕⊕ had tac levels ⊕ to 2-5 ng/ml. Tac was stopped and IV ganc reinstituted for LPD. A positive PCR with symptoms, but negative histology was defined as EBV disease; LPD was defined as histologic evidence of poly or monoclonal B cell proliferation. RESULTS: Forty children with survival > 2 mos have been enrolled. There were 18 children in Gp 1 (HR), mean age of 14±15 mo and mean follow-up time of 243±149 days, and 22 children in Gp 2 (LR), mean age of 64±65 mo and follow-up time of 275±130 days. The incidence of rejection was 27.7% in Gp 1 (HR) with 1 child requiring OKT3 and 40.9% in Gp 2 (LR) with 2 children requiring OKT3. In Gp 1 (HR), there was no LPD and 1 case of EBV disease (mononucleosis-like) which resolved. In Gp 2 (LR), there were 2 cases of LPD both resolved with stopping tac. Both children were 8 mos old at time of transplant. Neither received OKT3, both had 1 and 2 episodes of steroid sensitive rejection respectively. One child had EBV disease (mild hepatitis) which resolved. The% of pts with a persistent negative PCR were 17% in Gp 1, and 36% in Gp 2; the% of pts converting to positive PCR was 39% in Gp 1, and 32% in Gp 2; the% of pts always PCR positive was 45% in Gp 1, and 32% Gp 2; the% of pts with a peak PCR⊕ was 39% in Gp 1 and; 41% in Gp 2; and the% of pts with peak PCR⊕⊕ was 44% and Gp 1, 23% in Gp 2. CONCLUSIONS: Since instituting this protocol, the overall incidence of LPD has fallen from 10% to 4% for children receiving 1 ° tac therapy. No high risk pediatric liver recipient treated pre-emptively with IV ganc developed LPD. Both children with LPD were < 1 yr at OLT and considered low risk on the basis of positive pre-transplant recipient serology. These antibody titres may have been maternal in origin and not have offered long-term protection. Consideration should be given to prophylaxing all pediatric liver recipients < 1 yr with IV ganc for the first 3 mos after transplant.