Impaired cellular immunity is the main risk factor for VZV disease.
AlloHCT
~30% of alloHCT recipients with prior VZV infection experience reactivation without antiviral ppx. In chickenpox history, acyclovir PO for 1-2mo until 1y post-alloHCT significantly reduced VZV incidence (5% vs. 26% placebo). Post-ppx VZV rates were similar and mainly seen in patients needing systemic immunosuppression. Multiple studies confirm the benefit of 1y antiviral ppx (acyclovir, valacyclovir) post-alloHCT, reducing VZV rates (9% vs. 25% no ppx; P < .001) with no rebound VZV disease. However, lower-dose regimens were linked to higher VZV reactivation. NCCN Guidelines recommend VZV ppx ≥1 year after alloHCT in VZV+; longer if ongoing intensive systemic immunosuppressive therapy. HSV prophylaxis agents, at higher doses, are effective against VZV. In pediatric patients, routine VZV prophylaxis is not advised unless there’s a history of recurrent zoster or first-time zoster during myelosuppressive therapy, regardless of serostatus or vaccination history.
AutoHCT
HSV reactivation typically occurs in early neutropenic phase, while VZV risk extends up to a year. VZV prophylaxis for ≥6–12 months should be considered in post-transplant, hematologic malignancies with prolonged neutropenia, T-cell–depleting agents (fludarabine, alemtuzumab). Bortezomib and possibly carfilzomib increases VZV reactivation risk during treatment. Acyclovir, valacyclovir, famciclovir are effective. For CLL patients on alemtuzumab, prophylaxis is recommended until 2 months post-treatment and until CD4+≥200 cells/mcL.
Anticancer agent: alkylating (Bendamustine), antimetabolite (fludarabine), proteasome inhibitors (Bortezomib, Carfilzomib, Ixazomib),
BTKi (Ibrutinib, Acalabrutinib, Zanubrutinib, Pirtobrutinib), BCR::ABLi (Imatinib, Dasatinib, Nilotinib, Bosutinib, PONATinib, Asciminib),
PI3Ki (Inavolisib, Copanlisib, Duvelisib, Idelalisib, Umbralisib), mTOR (Everolimus, Sirolimus, Temsirolimus), JAKi (Momelotinib, Ruxolitinib, Fedratinib, Pacritinib), BiTE (Blinatumomab, Teclistamab-cgyv, Elranatamab-bcmm, Epcoritamab-bysp, Glofitamab-gxbm, Mosunetuzumab-axgb, Talquetamab-tgvs), antiCD20 (Rituximab, Obinutuzumab, Ofatumumab), antiCD30 (Brentuximab vedotin), antiCD38 (Daratumumab, Isatuximab), antiCD52 (Alemtuzumab), antiCD319/SLAMF7 (Elotuzumab), CCR4 (Mogamulizumab), IL6i (Tocilizumab, Siltuximab), ADC (Polatuzumab vedotin-piiq), CAR T-cell CD19 (Axi-cel, Brex-cel, Tisa, Liso-cel), CAR T-cell BCMA (Ide-cel, Cilta-cel)
Disease/condition: hematologic malignancies with prolonged neutropenia, CLL on Alemtuzumab
Recommend VZV ppx: proteasome inhibitor (Bortezomib, Carfilzomib, Ixazomib), BiTE (Teclistamab-cgyv, Elranatamab-bcmm, Epcoritamab-bysp, Glofitamab-gxbm, Mosunetuzumab-axgb, Talquetamab-tgvs), antiCD38 (Daratumumab, Isatuximab), antiCD52 (Alemtuzumab), antiCD319/SLAMF7 (Elotuzumab), CCR4 (Mogamulizumab), CAR T-cell CD19 (Axi-cel, Brex-cel, Tisa, Liso-cel),
CAR T-cell BCMA (Ide-cel, Cilta-cel)
Consider VZV ppx: BTKi (Ibrutinib, Acalabrutinib, Zanubrutinib, Pirtobrutinib), JAKi (Momelotinib, Ruxolitinib, Fedratinib, Pacritinib),
BiTE (Blinatumomab), antiCD20 (Rituximab, Obinutuzumab, Ofatumumab), antiCD30 (Brentuximab vedotin), ADC (Polatuzumab vedotin-piiq), anticipated neutropenia ≥7 days (≤500, or ≤1000 with ≤500 in 48h)
VZV vaccination in VZV- with proteasome inhibitors (Bortezomib, Carfilzomib, Ixazomib).
| Medication | Spectrum | ADE and Clinical Pearls |
| Acyclovir PO/IV | HSV/VZV | Prophylaxis PO (alloHCT, high risk, VZV+): 400–800 mg BID Post-VZV exposure prophylaxis: 800 mg 5 times daily Treatment PO/IV: Single dermatomal VZV: 800 mg PO 5 times daily or 10 mg/kg IV q8h for 7–10 daysDisseminated VZV including viral encephalitis: 10 mg/kg IV q8h ADE: nephropathy (hydration to avoid crystal nephropathy with high dose). Dosing based on ideal body weight. High-dose have been used as CMV ppx (but weak activity; ganciclovir, valganciclovir, foscarnet if high CMV risk). |
| Valacyclovir PO | HSV/VZV | Prophylaxis PO (VZV+, preferred over acyclovir PO): 500 mg BID Treatment PO (preferred over acyclovir PO): 1 g TID It have been used as CMV ppx (but weak activity; ganciclovir, valganciclovir, foscarnet if high CMV risk). |
| Famciclovir PO | HSV/VZV | Prophylaxis PO: 250 mg BID Treatment PO: 500 mg TID No data for oncologic-related prophylaxis |
| Foscarnet IV | HSV/VZV CMV HHV-6 | Treatment IV (acyclovir-resistant HSV drug of choice): 40 mg/kg q8h for 7–10 days ADE: nephrotoxic; monitor electrolytes Limited clinical data for HHV-6/HHV-8. Treatment should be reserved for clinically documented disease; ID consult is highly recommended. |
| Ganciclovir IV | HSV/VZV CMV | May cause bone marrow suppression Limited clinical data for HHV-6/HHV-8 |
| Valganciclovir PO | HSV/VZV CMV | May cause bone marrow suppression Limited clinical data for HHV-6/HHV-8 |
| Cidofovir IV | HSV/VZV CMV Adenovirus | Hydration and probenecid are required to reduce nephrotoxicity Ocular toxicity, bone marrow toxicity Evidence is limited for treatment of adenovirus; when used, ID consult is strongly recommended |
| Doses are for adults and in normal renal function. All require renal dosing | ||
Duration of VZV Prophylaxis
| Disease/Therapy | Duration |
| Proteasome inhibitors | During therapy and neutropenia period |
| Alemtuzumab AlloHCT GvHD requiring significant immunosuppression escalation | Consider for ≥1y after alloHCT |
| AutoHCT, lymphoma, MM, CLL, purine analog (fludarabine) | Consider ≥6-12 months after autoHCT |
Duration of VZV treatment: 7-10 days