Favorable Clinical Outcomes with Valacyclovir for Cytomegalovirus Prophylaxis Following Allogeneic Hematopoietic Cell Transplantation

Abstract

Introduction Current guidelines recommend monitoring and preemptive therapy for cytomegalovirus (CMV) reactivation in patients receiving allogeneic hematopoietic cell transplantation (HCT). Treatment options are limited by side effects such as myelosuppression and renal toxicity. Effective CMV prophylaxis may avoid these complications. At our institution, patients receiving a reduced intensity conditioning regimen of anti-thymocyte globulin (ATG) and total body irradiation (TBI) receive valacyclovir 1 gram every 8 hours as antiviral prophylaxis. Objectives The primary objective was to compare the incidence of CMV reactivation or disease after allogeneic HCT in patients receiving valacyclovir (VAL) versus acyclovir (ACV) for viral prophylaxis. Methods This was a retrospective, electronic medical review of allogeneic HCT recipients receiving VAL 1 gram every 8 hours vs. ACV 400 mg every 12 hours for viral prophylaxis between January 1, 2009 and July 31, 2018. Adult patients were included under the following conditions: first allogeneic HCT from a related or unrelated donor, patient or donor seropositive for CMV, and receipt of a reduced intensity conditioning regimen containing ATG. Patients were excluded if they received antiviral therapy for a non-CMV infection prior to CMV reactivation or received an umbilical cord or haploidentical transplant. Patients were matched based on propensity scoring. Results Forty-five patients were included in the VAL group and 35 in the ACV group. There was a significantly lower incidence of CMV reactivation or disease leading to preemptive therapy by day +180 in the VAL group vs. ACV group (18% vs. 57%, p=0.0004). No patients in the VAL group and four patients (11%) in the ACV group developed CMV disease (p=0.0331). While there was no difference in median time to CMV reactivation, 100% of patients who reactivated in the ACV group vs. 38% of those who reactivated in the VAL group did so within the first 60 days post-transplant. Potentially due to this later CMV reactivation, there was a trend towards less neutropenia while on CMV therapy in the VAL group vs. the ACV group (12% vs. 55%, p=0.0882). Median peak CMV titers were also not significantly different between groups, but five of the 20 patients who reactivated in the ACV group (25%) vs. no patients in the VAL group had titers greater than 10,000 copies/mL. Three patients in the ACV group (9%) vs. no patients in the VAL group required foscarnet due to myelosuppression or CMV resistance (p=0.2742). Overall survival was lower in the ACV group vs. VAL group (median time to death: 300 days vs. 679 days, p=0.0067). Conclusion Valacyclovir prophylaxis is associated with a lower incidence of CMV reactivation and disease vs. acyclovir prophylaxis. Patients who reactivate CMV on VAL prophylaxis may have fewer complications related to their reactivation.