Efficacy of Low-Dose Acyclovir Prophylaxis Against Varicella Zoster Virus in Pediatric Hematopoietic Stem Cell Transplantation Patients

Background: Prophylaxis with low-dose acyclovir is effective in lowering the incidence of Varicella zoster virus (VZV) reactivation and infections during the first year post-transplant in adult hematopoietic stem cell transplantation (HSCT) patients. Such data are lacking in the pediatric population. The objective of this study was to determine the effectiveness of low-dose acyclovir prophylaxis in preventing VZV reactivations and infections in the pediatric HSCT patients.

Methods Medical records of VZV seropositive patients, < 18 years of age who received a HSCT between January 2000 and April 2010 were retrospectively reviewed for: demographics, pre-transplant serology for herpes simplex virus, VZV and cytomegalovirus, acyclovir (ACV) dosing both intravenous (IV) and oral (PO), duration of acyclovir prophylaxis, incidence of reactivation, time to reactivation, age at reactivation, acyclovir prophylaxis status at the time of reactivation, severity of zoster infection, duration of follow-up, graft versus host disease (GVHD) prophylaxis, incidence of GVHD, treatment of acute or chronic GVHD, deaths, cause of death, and any adverse effects attributed to acyclovir. Data was analyzed using descriptive statistics.

Results:

DEMOGRAPHICS
N	88
Age in years (range)	6 ± 5.8* (0.67-18)
Male	63%
Donor Source
Bone Marrow	44
Peripheral Stem Cells	43
Umbilical Cord Blood	1
Stem Cell Dose (CD34 x106/kg body weight)	7.94 ± 6.45* (0.85-33)
Type of Transplantation
Autologous	32
Allogeneic	56
GVHD Prophylaxis
Cyclosporine and Methotrexate	32
Tacrolimus and Methotrexate	9
Other	11
OUTCOMES
PO ACV in mg/kg/dose (range)	9.8 ± 3.5* (2.4-28)
PO ACV in mg/dose (range)	200 ± 105* (100-400)
Duration of PO ACV in days (range)	345 ± 154*(7-1337)
Number of VZV Reactivations	1
Time from Transplantation to VZV Reactivation (range)	498 days
Deaths	3 (relapsed) 1 (cardiac arrest)
Deaths due to VZV	0

Conclusion: ACV at a median dose of 20 mg/kg/day twice daily was successful in preventing reactivations of VZV in 99 % of pediatric HSCT patients. The median duration of oral ACV prophylaxis in these patients was 345 days. Reactivation was detected by a qualitative polymerase chain reaction test positive for the viral DNA in a superficial tissue sample. Repeat test conducted three weeks later was negative. The patient was not on ACV at the time of reactivation, did not require treatment for VZV infection, but was started on valacylovir prophylaxis. According to the guidelines for preventing infectious complications among HSCT recipients, the recommended oral ACV dose for VZV prophylaxis is 60-80 mg/kg/day in two to three divided doses for children <40 kg body weight and 800 mg of oral ACV twice daily for children >40 kg body weight. At a dose lower than recommended, the incidence of VZV reactivation was low.