Abstract
BACKGROUND AND AIM: Though liver transplantation (LT) is effective for pediatric patients with end-stage liver disease, it is associated with complications such as graft-versus-host disease (GVHD). In part due to its rarity and lack of standardized therapy, post-LT GVHD is associated with a high mortality rate. While ruxolitinib (a JAK inhibitor) is approved for use in steroid-refractory GVHD, its safety/efficacy post-LT is undefined. Thus, this case study reports the use of ruxolitinib in a pediatric patient with post-LT GVHD. METHODS: A 5-month-old male underwent a deceased donor left lateral segment LT with an induction regimen of corticosteroid and tacrolimus. Four weeks post-LT, the patient developed skin GVHD. Ruxolitinib was administered in combination with tacrolimus and posaconazole, both capable of drug-drug interactions with ruxolitinib via modulation of CYP3A4 activity. A pharmacokinetic (PK) study was conducted to evaluate the use of ruxolitinib to induce GVHD remission. RESULTS: The ruxolitinib PK study revealed sufficient oral clearance and effective maximum serum concentration. Dosages of ruxolitinib, tacrolimus, and posaconazole were adjusted throughout the course of treatment based on GVHD severity (ruxolitinib) or their whole blood/plasma concentrations (tacrolimus and posaconazole). By 18 weeks after ruxolitinib initiation, skin GVHD lesions resolved and clinical remission was induced. The liver graft function was normal when assessed 40 months after the initial presentation of GVHD. CONCLUSIONS: This case illustrates the safe and effective PK-validated use of ruxolitinib with tacrolimus and posaconazole to successfully induce remission of post-LT GVHD in a pediatric patient.