A total of 230 patients were included in the retrospective analysis. These patients were divided into LTV (n = 133) and control (n = 97) groups on the basis of whether they had received LTV prophylaxis. LTV was administered at a dosage of 480 mg per day (or 240 mg per day for patients on cyclosporine), with prophylaxis starting at a median time of 7 days (range, 028 days) posttransplantation. The CMV-IgM, CMV-DNA and EBV-DNA statuses of the recipient/donor pairs were negative, whereas the CMV-IgG status of the recipient/donor pairs was positive before transplantation. Table 1 presents the clinical characteristics of the study population.

All patients were monitored weekly for CMV and EBV reactivation during the first 3 months after HSCT and then biweekly from 4 to 6 months. The cumulative incidence of EBV reactivation was 23% in the LTV group and 12% in the control group at 100 days post-HSCT and 26% and 12%, respectively, at 24 weeks. At 1 year after HSCT, EBV reactivation occurred in 36 patients (27%) and 13 patients (13%) in the LTV group and control group, respectively. The incidence of EBV reactivation was significantly different between the groups (χ² = 6.25, p = 0.012). All patients with EBV reactivation had EBV-DNAemia, while one patient in each group progressed to PTLD. The Kaplan‒Meier event rate of clinical EBV reactivation was 27.7% in the LTV group compared with 14.2% in the control group at one year posttransplantation (log-rank p = 0.023) (Fig. 1A).

The median time to EBV-DNAemia post-HSCT was 56 days (range, 20 to 204 days) in the LTV group and 52 days (range, 26 to 241 days) in the control group. The EBV-DNA loads varied between the groups. The proportion of patients with low EBV-DNA loads (> 5 × 102 to < 1 × 104 copies/mL) was significantly greater in the LTV group than in the control group (31 patients (23%) vs. 10 patients (10%); χ² = 6.47, p = 0.01). There was no significant difference in high EBV-DNA load reactivation (≥ 1 × 104 copies/mL) between the groups (χ² = 0.07, p = 0.78) (Fig. 1C).

At 1 year post-HSCT, the cumulative relapse rates, nonrelapse mortality rates, and overall survival rates were not significantly different between the LTV and control groups (12% vs. 10%, p = 0.68; 12% vs. 14%, p = 0.59; and 83% vs. 75%, p = 0.19, respectively) (Fig. 1B). Fewer patients in the LTV group than the control group had CMV reactivation, 46 patients (35%) vs. 54 patients (56%), respectively (χ² = 10.15, p < 0.002) (Fig. 1D). Twenty-one patients (17%) in the LTV group and 10 patients (10%) in the control group had concomitant CMV and EBV reactivation, with no significant difference between the groups (p = 0.24).

(A) Cumulative rate of clinical EBV reactivation (Letermovir group, solid line; control group, dotted line). (B) Cumulative rate of death from any cause (Letermovir group, solid line; control group, dotted line). (C) EBV-DNA load in cycles. (D) Clinical CMV reactivation