Objective To compare the occurrence of chickenpox in children with cancer who received varicella immunoglobulin (VZIG) or aciclovir as postexposure prophylaxis (PEP).

Design Prospective multicentre service evaluation of children with cancer who received either VZIG or aciclovir as PEP following significant exposure to varicella zoster virus (VZV) over a 24-month period from May 2018.

Setting Data were collected from 9 UK Paediatric Oncology Primary Treatment Centres.

Patients Children under 16 years old with a diagnosis of cancer and/or previous haematopoietic stem cell transplant who were VZV seronegative at exposure and/or diagnosis and received PEP following significant VZV exposure.

Main outcome measures The primary outcome was the incidence of breakthrough varicella within 6 weeks of VZV exposure and treatment with PEP.

Results A total of 105 eligible patients were registered with a median age of 4.9 years (range 1.1–10.5 years). Underlying diagnoses were acute leukaemia (64), solid tumours (22), Langerhans cell histiocytosis (9), central nervous system (CNS) tumours (8) and other (2). Aciclovir was received by 86 patients (81.9%), 18 received VZIG (17.1%) and 1 valaciclovir (0.9%). There were seven reported break-through VZV infections in 103 patients at follow-up (7/103, 6.8%). Clinical VZV developed in 5/84 of the aciclovir group (6.0%, 95% CI 2.0 to 13.3) and 2/18 of VZIG group (11.1%, 95% CI 1.4 to 34.7). All breakthrough infections were either mild (5/7) or moderate (2/7) in severity.

Conclusion Aciclovir is a safe and effective alternative to VZIG as VZV PEP in children with cancer and should be considered as standard of care.