Retrospective evaluation of sirolimus (mTOR blocker) for lymphatic malformations presenting in the neonatal period: a single-center experience.

BACKGROUND

Lymphatic malformations are rare vascular anomalies. Currently, there is no uniform approach to the treatment of these patients. Neonates with extensive disease often suffer from multiple complications, organ dysfunction, and various tissue lesions, which may be life-threatening and lead to aesthetic deformity. Treatment with sirolimus has the potential to improve symptoms and downsize the lesion, up to complete regression. This retrospective single-center study presents our experience with oral sirolimus in the treatment of newborns with lymphatic malformations, evaluating its efficacy and safety.

METHODS

A retrospective analysis was conducted on 23 patients in the neonatal period and early infancy with lymphatic malformations, treated at the St. Petersburg State Pediatric Medical University between 2021 and 2025. Seven patients underwent primary radical surgical treatment and were not included in the analysis. The final study cohort consisted of 16 patients who received primary conservative therapy with sirolimus. Fifteen out of 16 patients started receiving oral sirolimus before the age of 28 days of life. The median age at the commencement of treatment was 15 days after birth. After instrumental and laboratory examination, sirolimus was administered at a starting reduced dose of 0.5 mg/m2/day divided into two daily doses, followed by a gradual increase under clinical and laboratory monitoring. The therapeutic concentration of sirolimus in the blood (5-15 ng/mL) was monitored once a week.

RESULTS

Disease stabilization or regression was achieved in all 16 patients (100%), with a partial or complete radiological response (≥50% volume reduction) in 13 patients (81.25%) and complete regression (>90% volume reduction) in 10 patients (62.5%) at the 6-month assessment. No treatment-related serious adverse events requiring permanent discontinuation were observed. Recorded adverse events included transient respiratory infections (n = 2), diarrhea (n = 2), aphthous stomatitis (n = 1), and mild anemia (n = 1), all of which resolved with supportive care or temporary dose adjustment.

CONCLUSION

In this selected cohort, sirolimus demonstrated an acceptable safety and efficacy profile, supporting its feasibility as a conservative first-line strategy in neonates with extensive or unresectable lymphatic malformations. However, larger prospective studies are needed to confirm these findings.