Safety and efficacy of thalidomide in patients with transfusion-dependent β-thalassemia: a randomized clinical trial

被引：26

作者：

Chen, Jiang-Ming ^{[1
]}

Zhu, Wei-Jian ^{[2
]}

Liu, Jie ^{[3
,4
]}

Wang, Gui-Zhen ^{[3
]}

Chen, Xiao-Qin ^{[5
,6
]}

Tan, Yun ^{[7
]}

Xu, Wei-Wei ^{[1
]}

Qu, Li-Wei ^{[3
,8
,9
]}

Li, Jin-Yan ^{[1
]}

Yang, Huan-Ju ^{[1
]}

Huang, Lan ^{[1
]}

Cai, Ning ^{[1
]}

Wang, Wei-Da ^{[5
,6
]}

Huang, Ken ^{[10
]}

Xu, Jian-Quan ^{[11
]}

Li, Guo-Hui ^{[12
]}

He, Sheng ^{[13
]}

Luo, Tian-Ying ^{[1
]}

Huang, Yi ^{[14
]}

Liu, Song-Hua ^{[15
]}

Wu, Wen-Qiang ^{[16
]}

Lu, Qi-Yang ^{[1
]}

Zhou, Mei-Guang ^{[1
]}

Chen, Shu-Ying ^{[1
]}

Li, Rong-Lan ^{[1
]}

Hu, Mei-Ling ^{[1
]}

Huang, Ying ^{[1
]}

Wei, Jin-Hua ^{[17
]}

Li, Jun-Min ^{[7
]}

Chen, Sai-Juan ^{[7
]}

Zhou, Guang-Biao ^{[3
]}

机构：

[1] Wuzhou Gongren Hosp, Dept Hematol, Wuzhou 543001, Guangxi, Peoples R China

[2] Jinan Univ, Zhuhai Hosp, Zhuhai Peoples Hosp, Dept Hematol, Zhuhai 541000, Guangdong, Peoples R China

[3] Chinese Acad Med Sci & Peking Union Med Coll, State Key Lab Mol Oncol, Natl Canc Ctr, Natl Clin Res Ctr Canc,Canc Hosp, Beijing 100021, Peoples R China

[4] Hebei North Univ, Dept Reprod Med, Affiliated Hosp 1, Zhangjiakou 075000, Hebei, Peoples R China

[5] Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Canc Ctr, Guangzhou 510060, Guangdong, Peoples R China

[6] Sun Yat Sen Univ, Med Oncol Dept, Canc Ctr, Guangzhou 510060, Guangdong, Peoples R China

[7] Shanghai Jiao Tong Univ, Shanghai Inst Hematol, Natl Res Ctr Translat Med, State Key Lab Med Genom,Ruijin Hosp,Sch Med, Shanghai 200025, Peoples R China

[8] Chinese Acad Sci, Inst Zool, State Key Lab Membrane Biol, Beijing 100101, Peoples R China

[9] Univ Chinese Acad Sci, Beijing 100101, Peoples R China

[10] Youjiang Med Univ Nationalities, Dept Pediat, Affiliated Hosp, Baise City 533000, Guangxi, Peoples R China

[11] Yulin Guinan Hosp, Dept Hematol, Yulin 537005, Guangxi, Peoples R China

[12] Wuzhou Gongren Hosp, Dept Neurol, Wuzhou 543001, Guangxi, Peoples R China

[13] Guangxi Zhuang Autonomous Reg Women & Children Hl, Guangxi Key Lab Basic Res Birth Defects Prevent &, Nanning 530000, Guangxi, Peoples R China

[14] Guigang Peoples Hosp, Dept Hematol, Guigang 537100, Guangxi, Peoples R China

[15] Hosp Tradit Chinese Med Wuzhou City, Dept Hematol, Wuzhou 543002, Guangxi, Peoples R China

[16] Wuzhou Red Cross Hosp, Dept Hematol, Wuzhou 543002, Guangxi, Peoples R China

[17] Hechi Peoples Hosp, Dept Hematol, Hechi City 547000, Guangxi, Peoples R China

来源：

SIGNAL TRANSDUCTION AND TARGETED THERAPY | 2021年 / 6卷 / 01期

基金：

中国国家自然科学基金;

关键词：

FETAL-HEMOGLOBIN PRODUCTION; GLOBIN GENE-EXPRESSION; ERYTHROPOIESIS; POMALIDOMIDE; HYDROXYUREA; THERAPY;

D O I：

10.1038/s41392-021-00811-0

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Thalidomide induces gamma-globin expression in erythroid progenitor cells, but its efficacy on patients with transfusion-dependent beta-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 non beta 0/beta 0 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.

引用

页数：7

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