Abstract 3 Efficacy of Foscarnet in Preventing HHV6 Encephalitis in Adult Single Cord Blood Transplantation

Abstract Introduction The risk of HHV-6 encephalitis is high in cord blood transplantation (CBT) and the prognosis after encephalitis is poor, but there is no clarity regarding effective prevention methods for HHV-6 encephalitis. Objectives We retrospectively evaluated the effect of foscarnet (FCN) in preventing HHV-6 encephalitis in CBT. Methods We included 184 patients who underwent single CBT at Kyoto University Hospital from 2005 to 2022. For those who developed HHV-6 encephalitis, we calculated cumulative steroid doses from transplantation to the date of encephalitis onset, and for those who did not develop encephalitis, we calculated them to 25 days (the median encephalitis onset). Results Median (range) age was 49 years (18-70 years); 82% used tacrolimus and MMF for GVHD prophylaxis; FCN was used prophylactically or preemptively in 141 patients (77%) to prevent HHV6 encephalitis. FCN was used in 35% of patients from day 7 post-transplant, 20% from the time of HHV-6 reactivation, and 8% after the start of steroid administration. HHV-6 encephalitis occurred in 18 (10%) of 184 patients. The median cumulative steroid dose for those receiving steroids was 4.0 mg/kg. Steroid dose (mg/kg) had a significant effect on the development of encephalitis (HR 1.09, P=0.003); pre-engraftment immune reaction had no significant effect. The ROC curve showed that the cutoff for cumulative steroid dose that best predicted the development of encephalitis was 6.5 mg/kg. FCN prophylaxis showed no significant effect in preventing HHV6 encephalitis in the high-steroid group. However, FCN prophylaxis reduced the incidence of HHV6 encephalitis in the low-steroid group with marginal significance (HR 0.22, P=0.070). Patients who developed encephalitis without HHV6 prophylaxis had a significantly lower survival rate than those who did not develop encephalitis (1yr-OS, 25% vs. 69%). However, those who developed encephalitis during HHV6 prophylaxis did not differ significantly from those who did not develop encephalitis (1yr-OS, 59% vs. 69%) (Figure). Discussion FCN prophylaxis significantly reduced the incidence of encephalitis in the low-dose steroid group, whereas prophylaxis was not effective in the high-dose steroid group. However, prophylactic administration may improve the prognosis after the onset of encephalitis.