中国儿童淋巴瘤协作组成熟B细胞淋巴瘤2017方案治疗儿童高级别B细胞淋巴瘤中期疗效分析  

Interim efficacy of a multicenter cohort study for China Net Childhood Lymphoma mature B-cell lymphoma 2017 regimen in the treatment of pediatric High-grade-B cell lymphoma

作　　者：赵旸[1] 黄爽[2] 贾月萍[1] 张乐萍[1] 段彦龙[2] 金玲[2] 翟晓文 王宏胜 胡波 刘英 刘安生[5] 刘炜 郑敏翠[7] 李府[8] 孙立荣[9] 袁晓军[10] 戴云鹏[11] 张宝玺[12] 江莲[13] 王西阁[14] 王红梅 周春菊[16] 高子芬[17] 张永红 Zhao Yang;Huang Shuang;Jia Yueping;Zhang Leping;Duan Yanlong;Jin Ling;Zhai Xiaowen;Wang Hongsheng;Hu Bo;Liu Ying;Liu Ansheng;Liu Wei;Zheng Mincui;Li Fu;Sun Lirong;Yuan Xiaojun;Dai Yunpeng;Zhang Baoxi;Jiang Lian;Wang Xige;Wang Hongmei;Zhou Chunju;Gao Zifen;Zhang Yonghong(Department of Pediatrics,Peking University People′s Hospital,Beijing 100044,China;Medical Oncology Department,Pediatric Oncology Center,Beijing Children′s Hospital,Capital Medical University,National Center for Children′s Health,Beijing Key Laboratory of Pediatric Hematology Oncology,Key Laboratory of Major Diseases in Children,Ministry of Education,Beijing 100045,China;Department of Hematology,Children′s Hospital of Fudan University,National Children′s Medical Center,Shanghai 201102,China;Department of Pediatric Lymphoma,Beijing GoBroad Boren Hospital,Beijing 100070,China;Department of Hematology&Oncology,Xi′an Children′s Hospital,Xi′an 710002,China;Department of Hematology&Oncology,Zhengzhou Children′s Hospital,Zhengzhou 450018,China;Department of Hematology,Hunan Children′s Hospital,Changsha 410007,China;Hematology&Oncology Department,Children′s Hospital Affiliated to Shandong University,Jinan 250022,China;Department of Pediatric Hematology&Oncology,the Affiliated Hospital of Qingdao University,Qingdao 266003,China;Department of Pediatric Hematology/Oncology,Xinhua Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200092,China;Department of Pediatric Hematology&Endocrinology,Shandong Provincial Hospital Affiliated to Shandong First Medical University,Jinan 250021,China;Department of Pediatrics,Second Hospital of Hebei Medical University,Shijiazhuang 050004,China;Department of Pediatrics,Forth Hospital of Hebei Medical University,Shijiazhuang 050004,China;Department of Hematology and Oncology,Third Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;Department of Pediatric Hematology&Endocrinology,First Hospital of Shandong First Medical University,Jinan 250021,China;Pathology Department,Beij

机构地区：[1]北京大学人民医院儿科,北京100044 [2]国家儿童医学中心,首都医科大学附属北京儿童医院儿童肿瘤中心肿瘤内科,儿童血液病与肿瘤分子分型北京市重点实验室,儿科重大疾病研究教育部重点实验室,北京100045 [3]国家儿童医学中心,复旦大学附属儿科医院血液科,上海201102 [4]北京高博博仁医院儿童淋巴瘤科,北京100070 [5]西安市儿童医院血液肿瘤科,西安710002 [6]郑州儿童医院血液肿瘤科,郑州450018 [7]湖南省儿童医院血液内科,长沙410007 [8]山东大学附属儿童医院(济南市儿童医院)血液肿瘤科,济南250022 [9]青岛大学附属医院儿童医学中心儿童血液肿瘤科,青岛266003 [10]上海交通大学医学院附属新华医院小儿血液肿瘤科,上海200092 [11]山东第一医科大学附属山东省立医院小儿血液内分泌科,济南250021 [12]河北医科大学第二医院儿科,石家庄050004 [13]河北医科大学第四医院儿科,石家庄050004 [14]郑州大学第三附属医院血液/肿瘤科,郑州450052 [15]山东第一医科大学第一附属医院血液/肿瘤科,济南250012 [16]国家儿童医学中心,首都医科大学附属北京儿童医院病理科,北京100045 [17]北京大学第三医院病理科,北京100191

出　　处：《中华医学杂志》2024年第29期2751-2758,共8页National Medical Journal of China

基　　金：北京市卫生健康委员会北京市临床重点专科项目(2199000726)

摘　　要：目的分析中国儿童淋巴瘤协作组成熟B细胞淋巴瘤2017(CNCL-B-NHL-2017)方案治疗儿童高级别B细胞淋巴瘤(HGBL)的中期疗效。方法回顾性收集中国儿童淋巴瘤协作组(CNCL)16家医院2017年5月至2021年4月收治的年龄≤18岁的HGBL患儿的临床及病理资料,根据2016版世界卫生组织(WHO)造血和淋巴组织肿瘤分类,分为高级别B细胞淋巴瘤伴双打击/三打击(HGBL-DH/TH)组及高级别B细胞淋巴瘤-非特指型(HGBL-NOS)组。2组患儿均根据CNCL-B-NHL-2017方案,并按照危险度分层化疗,随访截止日期为2023年12月31日。所有患儿均行染色体荧光原位杂交(FISH)检查,以明确基因MYC、BCL-2及BCL-6重排情况。分析患儿发病时临床、病理特点,比较不同临床分期、危险度分组患儿的治疗效果,采用Kaplan-Meier法绘制生存曲线,log-rank检验比较组间累积生存率的差异,多因素Cox回归模型分析预后的影响因素。结果共纳入62例患儿,发病年龄[M(Q_(1),Q_(3))]为7(4,11)岁,男48例、女14例。临床分期Ⅱ、Ⅲ、Ⅳ期分别有11例(17.7%)、33例(53.2%)、18例(29.1%)。FISH检测结果显示4例(6.5%)为HGBL-DH;3例(4.8%)为HGBL-TH;余55例(88.7%)均为HGBL-NOS,其中18例伴MYC基因重排。HGBL-DH/TH组有7例,HGBL-NOS组有55例。B1方案13例(20.9%),B2方案3例(4.8%),C1方案37例(59.6%)和C2方案9例(14.7%)。48例(77.4%)同时联合利妥昔单抗靶向治疗。5例(8.0%)治疗中进展。随访时间[M(Q_(1),Q_(3))]为43.5(36.1,53.7)个月,所有患儿的完全缓解率为91.9%(57/62)。3年总生存率和无事件生存率分别为93.5%和91.9%。HGBL-NOS组患儿的3年总生存率高于HGBL-DH/TH组(96.3%比71.4%,P=0.011)。HGBL-NOS组3年无事件生存率高于HGBL-DH/TH组(94.5%比71.4%,P=0.037)。在HGBL-NOS亚组中,伴有MYC基因重排的患儿总生存率较低(100%比88.9%,P=0.039)。多因素Cox回归分析显示,中枢神经系统侵犯(HR=6.05,95%CI:1.96~38.13,P=0.046)是总生存率的危险因素。结论应用CNCL-B-NHL-201Objective To analyze the mid-term efficacy of the China Net Childhood Lymphoma mature B-cell lymphoma 2017(CNCL-B-NHL-2017)regimen in treating children with high-grade B-cell lymphoma(HGBL).Methods Clinical and pathological data of HGBL children aged≤18 years admitted to 16 hospitals of the Chinese Children′s Lymphoma Collaborative Group(CNCL)from May 2017 to April 2021 were collected retrospectively.They were divided in to high-grade B-cell lymphoma with double hit/triple hit(HGBL-DH/TH)group and high-grade B-cell lymphoma non-specified(HGBL-NOS)group,according to the 2016 version of the World Health Organization(WHO)Hematopoietic and Lymphoid Tissues Cancer Classification.Both groups of patients were treated with stratified chemotherapy by risk according to the CNCL-B-NHL-2017 scheme.The deadline for follow-up was December 31,2023.All the patients were examined by chromosome fluorescence in situ hybridization(FISH),and the rearrangement of genes MYC,BCL-2 and BCL-6 was confirmed.The clinical and pathological characteristics of patients at disease onset were analyzed,and the therapeutic effects of patients in different clinical stages and risk groups were compared.Survival analysis was drawn by Kaplan Meier method,the log-rank test was used to compare the differences in the cumulative survival rate between different groups,and multivariate Cox regression model was used to identify the prognostic factors.Results A total of 62 patients were included,with an onset age[M(Q_(1),Q_(3))]of 7(4,11)years,including 48 males and 14 females.There were 11(17.7%)patients in stageⅡ,33(53.2%)patients in stageⅢand 18(29.1%)patients in stageⅣ.FISH testing showed that 4 cases(6.5%)were HGBL-DH and 3(4.8%)were HGBL-TH.The remaining 55 cases(88.7%)were HGBL-NOS,with 18 cases accompanied by MYC rearrangement.There were 7 cases in the HGBL-DH/TH group and 55 cases in the HGBL-NOS group.Thirteen cases(20.9%)were treated with the B1 regimen,3 cases(4.8%)with B2 regimen,37 cases(59.6%)with C1 regimen,and 9 cases(14.7%)with the

关 键 词：淋巴瘤 B细胞 儿童 治疗 预后 

分 类 号：R733.1[医药卫生—肿瘤]