Sirolimus plus prednisolone vs sirolimus monotherapy for kaposiform hemangioendothelioma: a randomized clinical trial

被引:66
作者
Ji, Yi [1 ]
Chen, Siyuan [2 ]
Zhou, Jiangyuan [1 ]
Yang, Kaiying [1 ]
Zhang, Xuepeng [1 ]
Xiang, Bo [1 ]
Qiu, Tong [1 ]
Gong, Xue [1 ]
Zhang, Zixin [1 ]
Lan, Yuru [1 ]
Hu, Fan [3 ]
Kong, Feiteng [4 ]
Qiu, Qingxia [5 ]
Zhang, Yongbo [6 ]
机构
[1] Sichuan Univ, Div Oncol, Dept Pediat Surg, West China Hosp, Chengdu, Peoples R China
[2] Sichuan Univ, Pediat Intens Care Unit, Dept Crit Care Med, West China Hosp, Chengdu, Peoples R China
[3] Sichuan Univ, West China Univ Hosp 2, Dept Vasc Intervent Radiol, Chengdu, Peoples R China
[4] Sichuan Women & Childrens Hosp, Dept Pediat Surg, Chengdu, Peoples R China
[5] Chengdu Shangjin Nanfu Hosp, Dept Pediat Surg, Chengdu, Peoples R China
[6] Chengdu Women & Childrens Cent Hosp, Dept Pediat Surg, Chengdu, Peoples R China
基金
中国国家自然科学基金;
关键词
KASABACH-MERRITT PHENOMENON; THERAPY; INFANTS; VINCRISTINE; FIBROSIS;
D O I
10.1182/blood.2021014027
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The Kasabach-Merritt phenomenon (KMP) in kaposiform hemangioendothelioma (KHE) is characterized by life-threatening thrombocytopenia and consumptive coagulopathy. This study compared the efficacy and safety of sirolimus plus prednisolone vs sirolimus monotherapy as treatment strategies for KHE with KMP in the largest cohort to date. Participants were randomized to receive either sirolimus in combination with a short course of prednisolone or sirolimus monotherapy for at least 12 months. The primary outcome was defined as achievement of a durable platelet response (platelet count >100 x 109/L) at week 4. Participants completed efficacy assessments 2 years after the initial treatment. At week 4, a durable platelet response was achieved by 35 of 37 patients given sirolimus and prednisolone compared with 24 of 36 patients given sirolimus monotherapy (difference 27.9%; 95% confidence interval, 10.0-44.7). Compared with the sirolimus monotherapy group, the combination treatment group showed improvements in terms of measures of durable platelet responses at all points during the initial 3-week treatment period, median platelet counts during weeks 1 to 4, increased numbers of patients achieving fibrinogen stabilization at week 4, and objective lesion responses at month 12. Patients receiving combination therapy had fewer blood transfusions and a lower total incidence of disease sequelae than patients receiving sirolimus alone. The frequencies of total adverse events and grade 3-4 adverse events during treatment were similar in both groups. The responses seen in patients with KHE with KMP were profound and encouraging, suggesting that sirolimus plus prednisolone should be considered a valid treatment of KHE with KMP. This trial was registered at www.clinicaltrials.gov as #NCT03188068.
引用
收藏
页码:1619 / 1630
页数:12
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