Foscarnet against human herpesvirus (HHV)-6 reactivation after allo-SCT: breakthrough HHV-6 encephalitis following antiviral prophylaxis

High incidences of human herpesvirus (HHV)-6 encephalitis have recently been reported from several Japanese SCT centers. To evaluate the effect of low-dose foscarnet (PFA) in preventing HHV-6 infection among recipients of unrelated BM or cord blood (CB), we examined consecutive cohorts without prophylaxis against HHV-6 (Cohort 1, n =51) and with PFA prophylaxis (Cohort 2, PFA 50 mg/kg/day for 10 days after engraftment, n = 67). Plasma real-time PCR assay was performed weekly. High-level reactivation defined as HHV-6 DNA >= 10(4) copies/mL by day 70 was the primary endpoint. No significant reduction of high-level reactivation was seen in Cohort 2 (19.4%) compared with Cohort 1 (33.8%, P = 0.095). A trend was identified toward fewer high-level HHV-6 reactivations in Cohort 2 among recipients of unrelated BM (P = 0.067), but no difference in incidence was observed among CB recipients (P = 0.75). Breakthrough HHV-6 encephalitis occurred following PFA prophylaxis in three patients, and incidence of HHV-6 encephalitis did not differ between Cohort 1 (9.9%) and Cohort 2 (4.5%, P = 0.24). In conclusion, 50 mg/kg/day of PFA does not effectively suppress HHV-6 reactivation and cannot prevent all cases of HHV-6 encephalitis. To effectively prevent HHV-6 encephalitis, alternative approaches based on the pathogenesis of HHV-6 encephalitis will probably be required. Bone Marrow Transplantation (2013) 48, 257-264; doi:10.1038/bmt.2012.121; published online 2 July 2012