Successful treatment of Kasabach-Merritt phenomenon arising from Kaposiform hemangioendothelioma by sirolimus.

To the Editor: Kasabach-Merritt phenomenon (KMP) is one of the life-threatening complications of Kaposiform hemangioendothelioma (KHE) and is associated with a high mortality rate. KMP is characterized by enlarging vascular tumor, thrombocytopenia, and consumptive coagulopathy.1 We describe a successful therapy using oral sirolimus for KHE complicated with KMP, which failed to respond to multiple interventions. A 4-month-old girl presented to our hospital with a facial mass. Physical examination revealed a firm, poorly demarcated, violaceous, and smooth tumor (4 1 3 cm) on the right head and cheek area, with no signs of inflammation. Complete blood count at presentation showed hemoglobin level of 11.6 g/dL and platelets count of 158 10/L. Subsequently, the platelet count decreased to 37 10/L, and she also had hypofibrinogenemia (the fibrinogen level was 84mg/dL; normal being, 200 to 400mg/dL). The relevant hematological investigations carried out during following weeks are shown in Figure 1. The clinical findings and laboratory investigations strongly suggested the diagnosis of KHE with KMP. Biopsy of the tumor was not attempted because of the potential risk for hemorrhage. Following diagnosis, we started propranolol (2mg/kg/d) in 2 divided doses for the initial 2 weeks. However, the platelet count dropped further to 24 10/L, and the mass enlarged in size. Thereafter, we switched to another therapeutic regimen with intravenous methylprednisolone (4mg/ kg/d) and vincristine (0.05mg/kg/wk). This therapy was continued for 14 weeks. One week following this regimen, the size of the lesion started to decrease and platelet count increased to 97 10/L. However, during the next 4 weeks, the platelet count dropped to 21 10/L, along with enlargement of the mass. At the 16th week of therapy, the platelet count was 8 10/ L. Magnetic resonance imaging of the neck showed tumor progression to right side of the trachea. She began to experience progressive respiratory symptoms with obvious growth of subcutaneous tumor and felt to be in imminent danger of respiratory arrest. With informed consent, we started sirolimus at a dose of 0.04mg/kg administered twice daily at 12-hour intervals. Within 3 weeks of sirolimus therapy, the platelet count rose from 8 10 to 247 10/L, the mass shrunk in size, the lesion became no longer palpable, and the skin less markedly discolored. After 8 months of sirolimus therapy, the patient was doing well with platelet count of 346 10/L and lesion size of 15 8 5mm. The average trough level of sirolimus during the therapy was 14.1 ng/mL. Thereafter, the dose was reduced to 0.02mg/kg twice a day. At latest follow-up, on September 2013, the trough level of sirolimus was 8.75 ng/mL. How well our patient will do in the long run, and whether sirolimus can be discontinued without rebound tumor growth is still unknown. Sirolimus has been shown to be efficacious in some children.2,3 Toxicity, when the trough levels are kept between 5 to 15 ng/mL, is usually manageable.4 The most common toxicities associated with sirolimus are mucositis, peripheral edema, hypertriglyceridemia, hypercholesterolemia, and elevated liver enzymes.5 We checked the serum levels of sirolimus every 2 weeks during the first month and every month subsequently. Dose adjustments were made to maintain the desired drug level. The trough levels should be kept