Pediatr Neurol. 2021 Dec;125:26-31. doi: 10.1016/j.pediatrneurol.2021.09.014. Epub 2021 Sep 25.
Prenatal Sirolimus Treatment for Rhabdomyomas in Tuberous Sclerosis.
Pediatric neurology
Daniel Ebrahimi-Fakhari, Gabrielle Stires, Eunice Hahn, Darcy Krueger, David Neal Franz
Affiliations
Affiliations
- Division of Neurology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of General Pediatrics, University Children's Hospital Muenster, Muenster, Germany. Electronic address: [email protected].
- Division of Neurology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
- The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
- Division of Neurology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. Electronic address: [email protected].
PMID: 34624607
DOI: 10.1016/j.pediatrneurol.2021.09.014
Abstract
BACKGROUND: In tuberous sclerosis, most cardiac rhabdomyomas regress spontaneously. In some cases, the tumors can cause life-threatening hemodynamic compromise requiring subsequent surgical resection. The mechanistic target of rapamycin inhibitors everolimus and sirolimus have shown to be effective treatments for multiple conditions. There are four reports of off-label treatment with transplacental sirolimus for fetal rhabdomyomas due to tuberous sclerosis complex. The optimal dosing regimen is unknown.
METHODS: We reviewed the medical records of all patients treated prenatally with sirolimus for rhabdomyomas. All fetuses had a clinical and molecular diagnosis of tuberous sclerosis complex (2012 Consensus Diagnostic Criteria, including a positive genetic test). Clinical history, mechanistic target of rapamycin inhibitor dosing and levels, outcome, and adverse events were reviewed after initiation of sirolimus treatment.
RESULTS: Three fetuses were treated with maternal sirolimus. Dosing regimens and subsequent trough levels differed from 1 mg/day to 6 mg/day and <1.0 ng/mL to 12.2 ng/mL. Cardiac rhabdomyomas gradually shrank in all patients. Growth restriction was noted in one patient. No severe adverse events occurred during the treatment period.
CONCLUSIONS: Maternal sirolimus appears to be a safe treatment option in prenatally detected rhabdomyomas with possible need for intervention. Follow-up visits with fetal ultrasound, echocardiography, and laboratory work should be performed weekly during the treatment period. The optimal dosing and trough level timepoints remain unclear. Based on our results, we recommend a sirolimus starting dose of at least 2 mg/m
Copyright © 2021 Elsevier Inc. All rights reserved.
Keywords: Cardiac tumor; Fetal; Maternal; Rapamycin; Sirolimus; Transplacental; Tuberous sclerosis; mTOR inhibitor
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