Conversion from tacrolimus to sirolimus as a treatment modality in de novo allergies and immune-mediated disorders in pediatric liver transplant recipients.

Abstract

De novo PTAID may develop in pediatric solid organ transplant recipients, have a diverse spectrum, and are occasionally treatment resistant. Previous reports showed resolution of immune cytopenias in solid organ transplant recipients following replacement of the calcineurin inhibitor tacrolimus with the mTOR inhibitor sirolimus. Herein we describe a retrospective review (2000-2017) of subjects who developed PTAID in whom immunosuppression was changed to sirolimus. Eight recipients (6 males) of either liver (n=7) or multivisceral transplant (n=1) suffered from severe, treatment-resistant PTAID and were switched from tacrolimus to sirolimus. The median age at transplant was 1year (range 0.5-2.4years). Six (75%) recipients developed de novo allergy and 2 immune-mediated diseases. The median age at presentation of PTAID was 2.7 (1.4-9)years at a median of 1.3 (0.25-8)years after transplantation. The median time from PTAID presentation to conversion to sirolimus was 1.8 (0.45-10)years. Complete resolution of symptoms was seen in 4 (50%) patients after a median of 12 (range 4-24)months including 2 patients with immune-mediated disease, 1 eczema, and 1 with eosinophilic colitis. One patient with multiple food allergies had a partial response and 3 (38%) had no response. None of the 8 recipients developed sirolimus-attributed adverse events or acute rejection during a median follow-up of 5 (0.6-8)years after the conversion. Immunosuppression conversion from tacrolimus to sirolimus can be an effective therapy in patients suffering severe or treatment-resistant PTAID, suggesting a potential role for tacrolimus in the pathogenesis of PTAID.