P23 Stabilization of aggressive disease in NRAS kaposiform lymphangiomatosis with sirolimus

Abstract

Abstract Kaposiform lymphangiomatosis (KLA) is a rare disorder of lymphatic vasculature characterized by infiltrative and multifocal lymphatic abnormalities. The disease course is often complicated by a severe coagulopathy and frequently involves the central conducting lymphatic vessels leading to large-volume chylous pleural/pericardial effusions and ascites. There is a significant morbidity and mortality with 5-year survival from time of diagnosis estimated to be 50%. The genetic basis of KLA has recently been described as somatic activating mutations of the RAS–MAPK pathway. A 14-month-old girl, previously well, presented with a massive pericardial effusion leading to cardiac tamponade and cardiac arrest, requiring emergency pericardial drainage and extracorporeal membrane oxygenation. The patient had a profound thrombocytopenia not responding to repeat transfusion. MRI of the thorax revealed extensive cystic lesions consistent with diffuse lymphatic disease. Clinical suspicion of KLA was confirmed by mediastinal biopsy revealing characteristic kaposiform spindle-shaped lymphatic endothelial cells. Targeted next-generation sequencing revealed a mutation in NRAS (p.Q61R) in 2% of sequenced reads. Treatment with mTOR inhibitor sirolimus plus vincristine rapidly stabilized her refractory thrombocytopenia and led to a rapid clinical improvement enabling extubation within 72 h. Repeat MRI 2 months later confirmed reduced lymphatic disease. Lymphatic disease remains stable after 18 months of sirolimus monotherapy with no significant adverse effects. KLA is an aggressive mosaic disease of the lymphatic vasculature with high morbidity and mortality. Early diagnosis is key to enabling targeted medical therapies in this cohort. Clinicians should be aware of this differential when presented with high-volume effusions and refractory thrombocytopenia.