With the recognition of the increased risk of HSV and VZV reactivation in seropositive patients who are expected to become profoundly immunosuppressed during cancer therapy, prophylaxis with antiviral medications has drastically reduced the incidence of disease, primarily in patients receiving high-dose chemotherapy and undergoing hematopoietic stem cell transplant (HSCT). The MSG systematic review identified a series of randomized controlled trials testing various antiviral prophylactic protocols. It concluded that there was a significant benefit to using acyclovir to prevent HSV oral infection (at 800 mg/d).[Level of evidence: I] In addition, the systematic review pointed out that HSV reactivation was reported in a similar prevalence whether acyclovir or valacyclovir was prescribed  and that the prevention of HSV reactivation was achieved in various dosing protocols of valacyclovir (500 or 1,000 mg/d).
The Centers for Disease Control and Prevention (CDC), the Infectious Diseases Society of America (IDSA), and the American Society for Blood and Marrow Transplantation (ASBMT) have published guidelines for the prevention of opportunistic infections in HSCT recipients, which have become a benchmark in this field.[28,29] This significant body of literature presents a global perspective on the prevention of viral infections. CDC, IDSA, and ASBMT concluded that acyclovir prophylaxis is recommended for all HSV seropositive allograft recipients. Valacyclovir instead of acyclovir has been ranked moderately as an effective prevention for HSV in HSCT; foscarnet was mentioned as a drug to avoid for routine HSV prophylaxis because of substantial renal toxicity.
These guidelines extend beyond the MSG systematic review, which failed to provide sufficient evidence (e.g., regarding CMV, VZV, and EBV infections) because the evidence available is not specific for infections with oral involvement. The guidelines of these three U.S. societies are in line with the recommendations of the German Society of Hematology  and the European Group for Blood and Marrow Transplantation.
Early diagnosis and prompt therapy remain hallmarks of management. Unfortunately, the available literature  and the CDC and ASBMT guidelines [28,29] do not refer to treatment recommendations once a viral infection is diagnosed. As with other infections, risk of systemic dissemination and morbidity/mortality increases with degree and duration of immunocompromisation. The infections can be fatal, depending on degree of immunosuppression.