Antiviral Prophylaxis for Neutropenic Patients

Introduction to Antiviral Prophylaxis

The National Comprehensive Cancer Network recommends acyclovir, valacyclovir, or famciclovir as first-line agents for viral prophylaxis in neutropenic patients, with the choice and duration determined by the specific viral risk and patient population 1, 2

Antiviral prophylaxis against HSV is recommended during neutropenia in HSV-seropositive patients receiving chemotherapy for acute leukemia 1
Antiviral prophylaxis against HSV is recommended during neutropenia in HSV-seropositive patients receiving allogeneic or autologous hematopoietic cell transplantation (HCT) 1, 3
Antiviral prophylaxis against HSV is recommended during neutropenia in HSV-seropositive patients receiving treatment with alemtuzumab (until at least 2 months after completion and CD4 counts ≥200 cells/mcL) 1
Antiviral prophylaxis against HSV is recommended during neutropenia in HSV-seropositive patients receiving high-dose corticosteroids or T-cell–depleting agents (e.g., fludarabine) 1
For patients with acyclovir-resistant HSV infection, foscarnet is the recommended alternative 1
For patients already receiving CMV prophylaxis, no additional HSV prophylaxis is needed if on ganciclovir or foscarnet, but HSV prophylaxis is required if on letermovir (lacks anti-HSV activity) 1

VZV prophylaxis is recommended for allogeneic HCT recipients for at least 1 year post-transplant (if VZV-seropositive) 1, 4
VZV prophylaxis is recommended for autologous HCT recipients for 6-12 months post-transplant 4
VZV prophylaxis is recommended for patients receiving bortezomib or carfilzomib therapy 4
VZV prophylaxis is recommended for patients with hematologic malignancies with prolonged neutropenia 4
VZV prophylaxis is recommended for patients receiving T-cell–depleting agents (e.g., fludarabine, alemtuzumab) 4
The same agents used for HSV prophylaxis (acyclovir, valacyclovir, famciclovir) can be used for VZV prophylaxis, but at higher doses 4

For HSV prophylaxis, the duration of prophylaxis should be during the period of neutropenia for acute leukemia patients 1
For HSV prophylaxis, the duration of prophylaxis should be during neutropenia and possibly longer for HCT recipients depending on immunosuppression 1
For VZV prophylaxis, the duration of prophylaxis should be at least 1 year after allogeneic HCT 4
For VZV prophylaxis, the duration of prophylaxis should be 6-12 months for autologous HCT recipients 4

HSV prophylaxis is indicated in children who are seropositive for the virus 1
For pediatric patients, VZV prophylaxis should not be routinely given unless there is a history of recurrent zoster infections or first zoster infection during myelosuppressive therapy 4

For CMV-seropositive allogeneic HCT recipients, letermovir prophylaxis (480 mg/day or 240 mg/day if taking ciclosporin) for 14 weeks post-transplant is effective 4
Alternative options for CMV prophylaxis include ganciclovir, valganciclovir, or foscarnet 5

Failure to screen for HSV seropositivity before initiating prophylaxis can be a common pitfall 1
Omitting HSV prophylaxis in patients receiving letermovir for CMV prophylaxis can be a common pitfall 1
Discontinuing prophylaxis too early in high-risk patients, especially those with ongoing immunosuppression, can be a common pitfall 1, 4