Managing HHV-6 Reactivation after Hematopoietic Stem Cell Transplantation with a Short Course Foscarnet Therapy

Background Available data on preemptive treatment (PT) for Human herpesvirus 6 (HHV6) reactivation after allogeneic stem cell transplantation (SCT) remains limited, and treatment guidelines are lacking. Objectives We hypothesized that PT with a 1-week course of foscarnet (FCN) at a lower plasma HHV6 viral load (VL) is effective in treating early HHV6 reactivation, obviating the need for in-hospital management and minimizing complications. Methods We reviewed outcomes of adult patients (pts) who received PT with once daily FCN x 1 week for HHV6 reactivation after SCT between 05/2020-9/2023. Plasma HHV6 VL was monitored using qPCR twice monthly in first 100 days and twice weekly after reactivation. We compared viral reactivation, transplant outcomes and recovery of T-cell subsets between the pts who experienced HHV6 reactivation and the control group of pts who did not. Results A total of 68 pts (44 haplo, 22 HLA-matched, 2 HLA-mismatched) with a median age of 49 years (range, 22-73) were included, of whom 18 developed HHV6 reactivation (26.5%). Cumulative incidence of HHV6 reactivation at 100-days was 28.1% (95% CI, 18%-39%), and was higher in haplo-donor compared to matched-HLA donor recipients but did not reach statistical significance (35% vs. 13.9%, P=0.08). The most common diagnosis was acute leukemia (13 pts). MAC and RIC were used in 6 and 12 pts, respectively.Median time to HHV6 reactivation was 24 days (range, 6-89), median VL was 2930 copies/mL (range, 188-118000) at first reactivation, and median peak VL was 10000 copies/mL (range, 600-983000). All pts received a short course of FCN dosed at either 90 mg/kg/day (N=14) or 60 mg/kg/day (N=4). Plasma HHV6 DNA was undetectable in all pts after completion of PT (100% response). No encephalitis occurred. The 100-day cumulative incidence of BKV reactivation/infection was higher in the HHV6 group (50% vs. 23.3%, P=0.01), but there was no difference in CMV (34.8% vs. 33.4%, P=0.53) and other virus (24.9% vs. 10.5%, P=0.37) reactivation/infection between 2 groups.All pts achieved neutrophil and platelet engraftment after a median time of 16 (8-24) and 23 (14-168) days, respectively, with no secondary graft failure. Absolute number of lymphocyte subsets (CD3/CD4/CD8/CD19/CD56) at days 100 and 180 showed no difference between the 2 groups. At 1-year, there was no difference between pts with or without HHV6 reactivation with regards to PFS (77.1% vs. 66.2%, P=0.79), OS (91.7% vs. 70%, P=0.57), NRM (8.6% vs. 21%, P=0.67) and relapse (14.3% vs. 12.8%, P=0.91). No complications related to FCN infusion were noted. One pt with a peak HHV6 DNAemia of 983000 experienced recurrent reactivation and received a second course of FCN with resolution of viremia. Conclusion A short course of once-daily FCN has a highly tolerability profile, is effective in clearing HHV6 viremia, may reduce incidence of HHV6-related complications and prevent hospitalization.