Ganciclovir Pharmacokinetic Monitoring in a Pediatric Stem Cell Transplant Recipient with Human Cytomegalovirus Viremia: A Case Report

Cytomegalovirus (CMV) reactivation following stem cell transplant (SCT) is reported to occur in 25-44.5% of pediatric patients when either donor or recipient is CMV positive. CMV after SCT is associated with hepatitis, colitis, pneumonitis, and increased risk of non-relapse mortality. Ganciclovir is standard therapy for treatment of CMV, but pharmacokinetic (PK) data are lacking in pediatric SCT. Recommended dosing is derived from adult data, and PK monitoring is rarely performed. High inter-individual variability has been shown in pediatric PK models, putting pediatric SCT patients at risk for inadequate ganciclovir exposure and increased risk of symptomatic CMV disease and antiviral resistance. The objective of this case report is to summarize a novel dosing strategy using area under the curve (AUC) PK monitoring to safely and effectively dose ganciclovir in a pediatric SCT patient with CMV viremia that has failed to clear using standard dosing. A 6-month-old CMV-negative male underwent allogeneic SCT from a CMV-positive, matched sibling donor for hemophagocytic lymphohistiocytosis. He developed asymptomatic CMV viremia on Day +36 post-SCT. He failed to clear CMV with standard valganciclovir and ganciclovir pediatric dosing; resistance testing was negative. Ganciclovir was empirically increased to 6 mg/kg/dose every 12 hours without success; foscarnet was added. Following serial two-point AUC calculations, a final dose of 15.3 mg/kg/dose every 12 hours—three times the recommended pediatric dose—was needed to achieve an AUC 80-120mg*L/h. After foscarnet discontinuation, ganciclovir was continued at home. At the final increased dose, CMV viremia cleared 150 days after starting antiviral therapy and 97 days after first AUC-based dose increase. No episodes of severe cytopenia or evidence of end-organ disease were observed. Letermovir was subsequently prescribed for secondary prophylaxis. Inadequate ganciclovir exposure may lead to treatment failure or antiviral resistance. To our knowledge, this is the first reported case of AUC -guided ganciclovir dosing in a pediatric SCT patient with CMV viremia. AUC-guided dosing is a potentially safe and effective option for pediatric patients unable to clear CMV with traditional dosing strategies.