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.
Herpes simplex virus
Oral herpetic lesions can range from routine herpes labialis to severe stomatitis causing large, painful ulcerations throughout the mouth. The severity of lesions dramatically increases with increasing degrees of immunosuppression. The incidence of recurrent oral HSV lesions in myelosuppressed cancer patients has been considerably reduced with the use of prophylactic acyclovir and valacyclovir regimens.[32,33,34] Additionally, the severity and duration of actual HSV lesions have been reduced by antiviral therapies.
Breakthrough infections are uncommon but can occur. While true resistance to antivirals occurs, clinical infection in the face of antiviral therapy is more likely caused by insufficient dosing or compromised gastrointestinal absorption of oral acyclovir. The introduction of valacyclovir appears to have reduced the incidence of breakthrough oral HSV infections. Topical therapy alone is generally not efficacious in the immunocompromised patient.
In patients who are not receiving antiviral prophylaxis, oral lesions typically emerge concurrent with chemotherapy or chemoradiation therapy during the period of most significant immunosuppression (white blood cell nadir). Typically, in HSCT patients, this represents the period a few days pretransplant through day 35 posttransplant. The risk of HSV reactivation remains higher than normal until immune reconstitution occurs. Similar patterns of risk are noted in patients who are receiving high-dose (immunosuppressive) chemotherapy.
Recurrent oral HSV infections occurring simultaneously with cancer therapy–induced oral mucositis can result in the development of extensive, confluent mucosal ulcerations clinically similar to primary herpetic stomatitis. As such, HSV stomatitis can be confused with cancer therapy–induced ulcerative mucositis. Viral cultures from lesions in HSV seropositive patients are essential for accurate diagnoses. Assays that produce more rapid results, including direct immunofluorescence, shell vial testing, and specific immunoassay for HSV antigen and/or biopsy, may also be useful.
Unlike in myelosuppressed cancer patients, incidence of HSV reactivation in patients undergoing head and neck radiation is very low. Therefore, HSV prophylaxis in patients scheduled to receive head and neck radiation is not recommended.