The importance of intermediate-dose Valacyclovir in primary CMV prophylaxis after Allogeneic-stem cell transplantation, and the advantages of step-wise pre-emptive treatment in CMV reactivation

Abstract

Objective: Cytomegalovirus (CMV) reactivation and disease are still one of the most important causes of morbidity and mortality after allogeneic stem cell transplantation (ASCT). Letermovir prophylaxis has been clearly shown to be effective and well-tolerated. Drug interactions and cost are limitations. Alternative regimens such as Valacyclovir 3g-6g a day are of interest. In our study, we investigated the clinical results of intermediate dose (3 gr/d) valacyclovir after ASCT in primary CMV prophylaxis. Material and Methods: The data of 70 patients who underwent ASCT between 2019-2020 were retrospectively analyzed. Valacyclovir was given at a dose of 3 g/day to all patients for primary CMV prophylaxis after ASCT. If CMV reactivation developed during Valacyclovir prophylaxis, therapeutic oral Valganciclovir or parenteral Ganciclovir was gradually switched according to CMV DNA copy numbers. Results: The mean age of the patients included in the study was 45.5 years. The D+/R+ seropositivity was 97.2%. CMV reactivation developed in 37/70 (52.8%) patients within the first 100 days after transplantation. While CMV negativity could be achieved with oral VValganciclovir in 17 of the reactive patients (45.9%), hospitalization was required for parenteral ganciclovir use in 20 (28.1%) of them. The median PFS of patients with and without CMV reactivation was 10 months and 18 months, with a one-year PFS were 49.9% and 80.9%, respectively. One-year overall survival rates of patients with and without CMV reactivation were 52.9% and 92.9% respectively. Conclusion: It has become more important to prevent infections that may develop after ASCT with prophylaxis rather than treating. Post-transplant intermediate-dose Valacyclovir as primary prophylaxis has been shown to reduce CMV reactivation/disease rates at desired levels and reduce hospitalizations.