GUIDANCE OF GANCICLOVIR THERAPY WITH PP65 ANTIGENEMIA IN CYTOMEGALOVIRUS-FREE RECIPIENTS OF LIVERS FROM SEROPOSITIVE DONORS1

Cytomegalovirus (CMV*), the first reported transplant-associated opportunistic virus (1), has remained the most frequent single cause or co-cause of infections throughout the ensuing three decades (2). Because prophylactic drug and hyperimmune globulin therapy has not been effective in these CMV-infected patients (2–4), Rubin (5) suggested withholding treatment until the phase of rapid viral replication (preemptive therapy). Early diagnosis of CMV infection, upon which this strategy depends, can be accomplished in the presymptomatic phase (6, 7) with a rapid quantitative direct demonstration of CMV antigen pp65 in cytospin preparations of peripheral blood leukocytes (PBL) (8, 9). This method has aided in the management of 20 CMV seronegative recipients of livers from seropositive donors, a circumstance that carries an 85–90% risk of virus transmission of CMV disease, presumably from migratory monocytes from the graft (10) that are known to harbor the latent virus in healthy seropositive individuals (11). The 20 recipients under tacrolimus/prednisone immunosuppression were followed for 308 ± 100.5 days (range, 63–520 days) after transplantation; a death at 63 days unrelated to CMV accounted for the only follow-up of 20 were considered positive. CMV IgG was also the routine test used for donor screening. Intravenous ganciclovir therapy (Cytovene; Syntex Pharmaceutical Ltd., Palo Alto, CA) was started only with the first detection of pp65 antigenemia, and continued until pp65 clearance. The ganciclovir dose was governed by creatinine clearance: >50 ml/min → 5 mg/kg of ganciclovir twice daily, 10–50 ml/min → 5 mg/kg every 24–48 hr, and