Safety and efficacy of thalidomide in patients with transfusiondependentβ-thalassemia:a randomized clinical trial  

作　　者：Jiang-Ming Chen Wei-Jian Zhu Jie Liu Gui-Zhen Wang Xiao-Qin Chen Yun Tan Wei-Wei Xu Li-Wei Qu Jin-Yan Li Huan-Ju Yang Lan Huang Ning Cai Wei-Da Wang Ken Huang Jian-Quan Xu Guo-Hui Li Sheng He Tian-Ying Luo Yi Huang Song-Hua Liu Wen-Qiang Wu Qi-Yang Lu Mei-Guang Zhou Shu-Ying Chen Rong-Lan Li Mei-Ling Hu Ying Huang Jin-Hua Wei Jun-Min Li Sai-Juan Chen Guang-Biao Zhou 

机构地区：[1]Department of Hematology,Wuzhou Gongren Hospital,Wuzhou 543001 Guangxi,China [2]Department of Hematology,Zhuhai People’s Hospital(Zhuhai Hospital Affiliated with Jinan University),Zhuhai 541000 Guangdong,China [3]State Key Laboratory of Molecular Oncology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China [4]Department of Reproductive Medicine,The First Affiliated Hospital of Hebei North University,Zhangjiakou 075000 Hebei,China [5]State Key Laboratory of Oncology in South China,Collaborative Innovation Center for Cancer Medicine,Medical Oncology Department,Sun Yat-Sen University Cancer Center,Guangzhou 510060 Guangdong,China [6]State Key Laboratory of Medical Genomics,Shanghai Institute of Hematology,National Research Center for Translational Medicine,Ruijin Hospital Affiliated with Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China [7]State Key Laboratory of Membrane Biology,Institute of Zoology,Chinese Academy of Sciences&University of Chinese Academy of Sciences,Beijing 100101,China [8]Department of Pediatrics,Affiliated Hospital of Youjiang Medical University for Nationalities,Baise City 533000 Guangxi,China [9]Department of Hematology,Yulin Guinan Hospital,Yulin 537005 Guangxi,China [10]Department of neurology,Wuzhou Gongren Hospital,Wuzhou 543001 Guangxi,China [11]Guangxi Key Laboratory of Basic Research on Birth Defects Prevention and Treatment,Guangxi Zhuang Autonomous Region Women and Children Health Care Hospital,Nanning 530000 Guangxi,China [12]Department of Hematology,Guigang People’s Hospital,Guigang 537100 Guangxi,China [13]Department of Hematology,Hospital of Traditional Chinese Medicine of Wuzhou City,Wuzhou 543002 Guangxi,China [14]Department of Hematology,Wuzhou Red Cross Hospital,Wuzhou 543002 Guangxi,China [15]Department of Hematology,Hechi People’s Hospital,Hechi City 547000 Guangxi,China

出　　处：《Signal Transduction and Targeted Therapy》2021年第12期3723-3729,共7页信号转导与靶向治疗（英文）

基　　金：This work was supported by the National Key Research and Development Program of China(No.2020YFA0803300);the CAMS Innovation Fund for Medical Sciences(CIFMS,Nos.2021-RC310-003,2020-RC310-002);CAMS Initiative for Innovative Medicine(2021-1-I2M-012);the Key Project of the National Natural Science Foundation of China(81830093);Guangxi Natural Science Foundation(2020GXNSFAA159097);the Funding for Guangxi Thalassemia Prevention Capacity Improvement Project,the Overseas Expertise Introduction Project for Discipline Innovation(111 Project,B17029);the Double First-Class Project(WF510162602)of Shanghai Jiao Tong University;Shanghai Collaborative Innovation Program on Regenerative Medicine and Stem Cell Research(2019CXJQ01);Shanghai Guangci Translational Medical Research Development Foundation.

摘　　要：Thalidomide inducesγ-globin expression in erythroid progenitor cells,but its efficacy on patients with transfusion-dependentβ-thalassemia(TDT)remains unclear.In this phase 2,multi-center,randomized,double-blind clinical trial,we aimed to determine the safety and efficacy of thalidomide in TDT patients.A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks,followed by an extension phase of at least 36 weeks.The primary endpoint was the change of hemoglobin(Hb)level in the patients.The secondary endpoints included the red blood cell(RBC)units transfused and adverse effects.In the placebo-controlled period,Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0(range,2.5 to 37.5)g/L,whereas Hb in patients treated with placebo did not significantly change.Within the 12 weeks,the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4±5.0 U and 10.3±6.4 U,respectively(P<0.001).Adverse events of drowsiness,dizziness,fatigue,pyrexia,sore throat,and rash were more common with thalidomide than placebo.In the extension phase,treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9±19.0 g/L,without blood transfusion.Significant increase in Hb concentration and reduction in RBC transfusions were associated with nonβ0/β0 and HBS1L-MYB(rs9399137 C/T,C/C;rs4895441 A/G,G/G)genotypes.These results demonstrated that thalidomide is effective in patients with TDT.

关 键 词：TRANSFUSION PATIENTS THALIDOMIDE 

分 类 号：R556.61[医药卫生—血液循环系统疾病]