三氧化二砷联合改良N7诱导方案治疗儿童高危神经母细胞瘤的多中心短期临床报告  

Short-term results of a multicenter study based on a modified N7 induction regimen combined with arsenic trioxide in the treatment of children with high-risk neuroblastoma

作　　者：杨舒 陈开澜[2] 何云燕[3] 彭晓敏[1] 熊昊[2] 贾文广[3] 吴沙 吉训琦[4] 陈玉雯[4] 田川 叶中绿 杨震[6] 祝建君 刘爱国[7] 田小华[8] 潘凤娟[8] 黄科[1] 周敦华[1] 方建培[1] 黎阳[1] Yang Shu;Chen Kailan;He Yunyan;Peng Xiaomin;Xiong Hao;Jia Wenguang;Wu Sha;Ji Xunqi;Chen Yuwen;Tian Chuan;Ye Zhonglü;Yang Zhen;Zhu Jianjun;Liu Aiguo;Tian Xiaohua;Pan Fengjuan;Huang Ke;Zhou Dunhua;Fang Jianpei;Li Yang(Department of Hematology and Oncology,Children's Medical Center,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China;Department of Oncology,Wuhan Children's Hospital,Tongji Medical College of Huazhong University of Science and Technology,Wuhan 430016,China;Department of Pediatrics,First Affiliated Hospital of Guangxi Medical University,Nanning 530021,China;Department of Hematology and Oncology,Hainan General Hospital,Haikou 570311,China;Department of Hematology and Oncology,Children′s Medical Center,Affiliated Hospital of Guangdong Medical University,Zhanjiang 524001,China;Department of Oncology,Kunming Children′s Hospital,Kunming 650000,China;Department of Pediatric Hematology and Oncology,Tongji Hospital,Tongji Medical College of Huazhong University of Science and Technology,Wuhan 430030,China;Department of Pediatrics,Guangdong Provincial Agricultural Reclamation Center Hospital,Zhanjiang 524000,China)

机构地区：[1]中山大学孙逸仙纪念医院儿童医学中心血液肿瘤科,广州510120 [2]华中科技大学同济医学院附属武汉儿童医院肿瘤科,武汉430016 [3]广西医科大学第一附属医院儿科,南宁530021 [4]海南省人民医院血液肿瘤科,海口570311 [5]广东医科大学附属医院儿童医学中心血液肿瘤科,湛江524001 [6]昆明市儿童医院肿瘤科,昆明650000 [7]华中科技大学同济医学院附属同济医院儿童血液肿瘤科,武汉430030 [8]广东省农垦中心医院儿科,湛江524000 [9]中山市人民医院儿科,中山528400

出　　处：《中华儿科杂志》2024年第10期949-955,共7页Chinese Journal of Pediatrics

基　　金：广州市特色技术项目(2023P-TS39);中山大学孙逸仙纪念医院医工融合培育专项(YXYGRH202202)。

摘　　要：目的探讨三氧化二砷(ATO)联合改良N7诱导方案治疗初治高危神经母细胞瘤(NB)的短期临床疗效及安全性。方法前瞻性、单臂、多中心Ⅱ期临床研究。以2019年1月至2023年8月中山大学孙逸仙纪念医院、华中科技大学同济医学院附属武汉儿童医院、广西医科大学第一附属医院、海南省人民医院、广东医科大学附属医院、昆明市儿童医院、华中科技大学同济医学院附属同济医院、广东省农垦中心医院8家单位收治的67例高危NB患儿为研究对象,均予ATO联合改良N7诱导方案化疗,对诱导化疗结束时的疗效及不良反应进行评估及分析,根据疗效评估结果分为治疗有反应组及治疗无反应组,采用Fisher确切概率法比较两组患儿临床特征的差异。结果67例高危NB患儿中男40例(60%)、女27例(40%);发病年龄3.5(2.6,4.8)岁;原发灶大多在腹膜后(含肾上腺)(56/67,84%);初诊时伴有远处淋巴结转移25例(37%)、骨转移48例(72%)、骨髓转移56例(84%)、中枢神经系统转移3例(4%);检测出MYCN基因扩增28例(42%)。在诱导化疗结束时完全缓解33例(49%),部分缓解29例(43%),疾病稳定1例(1%),疾病进展4例(6%);诱导化疗结束时客观缓解率为93%(62/67),疾病控制率为94%(63/67)。治疗无反应组初诊时中枢神经系统转移占比高于治疗有反应组[2/5比2%(1/62),P=0.013],而MYCN基因扩增情况在两组间差异无统计学意义[3/5比40%(25/62),P=0.786]。诱导化疗期间发生Ⅲ级及以上的不良反应有骨髓抑制60例(90%)、胃肠道症状33例(49%)、感染20例(30%),肝毒性4例(6%)和心血管毒性1例(2%),未出现与化疗相关的死亡。结论ATO联合改良N7诱导方案具有良好的疗效及安全性,值得在临床中进一步推广。ObjectiveTo analyze the short-term clinical efficacy and safety of arsenic trioxide(ATO)combined with a modified N7 induction regimen in the treatment of children with high-risk neuroblastoma(NB).MethodsThis study was a prospective,single-arm,multicenter phaseⅡclinical study.Sixty-seven high-risk NB children from eight units of Sun Yat-sen Memorial Hospital of Sun Yat-sen University,Wuhan Children′s Hospital of Tongji Medical College of Huazhong University of Science and Technology,First Affiliated Hospital of Guangxi Medical University,Hainan General Hospital,Affiliated Hospital of Guangdong Medical University,Kunming Children′s Hospital,Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology,and Guangdong Provincial Agricultural Reclamation Center Hospital were enrolled from January 2019 to August 2023 and were treated with ATO combined with a modified N7 induction regimen.The efficacy and adverse effects at the end of induction chemotherapy were assessed and analyzed,and the differences in the clinical characteristics were further compared between the treatment-responsive and treatment-unresponsive groups by using the Fisher′s exact test.ResultsAmong 67 high-risk NB children,there were 40 males(60%)and 27 females(40%),with the age of disease onset of 3.5(2.6,4.8)years.Primary NB sites were mostly in retroperitoneum(including adrenal gland)(56/67,84%)and the common metastases sites at initial diagnosis were distant lymph node in 25 cases(37%),bone in 48 cases(72%),bone marrow in 56 cases(84%)and intracalvarium in 3 cases(4%).MYCN gene amplification were detected in 28 cases(42%).At the end of induction,33 cases(49%)achieved complete remission,29 cases(43%)achieved partial remission,1 case(1%)with stable disease,and 4 cases(6%)were assessed as progressive disease(PD).The objective remission rate was 93%(62/67)and the disease control rate was 94%(63/67).The percentage of central system metastases at the initial diagnosis was higher in the treatment-unresponsive group tha

关 键 词：神经母细胞瘤 砷剂 儿童 多中心研究 

分 类 号：R739.4[医药卫生—肿瘤]