化疗延迟对儿童伯基特淋巴瘤预后影响的多中心研究  

A multicenter study on effect of delayed chemotherapy on prognosis of Burkitt lymphoma in children

作　　者：宋丽[1] 金玲[2] 张永红 杨晓梅[1] 段彦龙[2] 郑敏翠[4] 翟晓文 刘英 刘炜 刘安生[7] 袁晓军 戴云鹏[9] 张乐萍[10] 汪俭 孙立荣[12] 刘嵘[13] 张宝玺[14] 江莲[15] 魏会霞[16] 陈开澜[17] 金润铭[18] 王西阁[19] 周海霞[20] 王红美 庄树栓 周春菊[23] 高子芬[24] 牟晓 张开慧[25] 李府[1] Song Li;Jin Ling;Zhang Yonghong;Yang Xiaomei;Duan Yanlong;Zheng Mincui;Zhai Xiaowen;Liu Ying;Liu Wei;Liu Ansheng;Yuan Xiaojun;Dai Yunpeng;Zhang Leping;Wang Jian;Sun Lirong;Liu Rong;Zhang Baoxi;Jiang Lian;Wei Huixia;Chen Kailan;Jin Runming;Wang Xige;Zhou Haixia;Wang Hongmei;Zhuang Shushuan;Zhou Chunju;Gao Zifen;Mu Xiao;Zhang Kaihui;Li Fu(Department of Hematology&Oncology,Children′s Hospital Affiliated to Shandong University(Jinan Children′s Hospital),Jinan 250022,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 Pediatric Lymphoma,Beijing GoBroad Boren Hospital,Beijing 100070,China;Department of Hematology,Hunan Children′s Hospital,Changsha 410007,China;Department of Hematology,Children′s Hospital of Fudan University,National Children′s Medical Center,Shanghai 201102,China;Department of Hematology&Oncology,Zhengzhou Children′s Hospital,Zhengzhou 450018,China;Department of Hematology&Oncology,Xi′an Children′s Hospital,Xi′an 710002,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,Peking University People′s Hospital,Beijing 100044,China;Department of Hematology&Oncology,Anhui Children′s Hospital,Hefei 230022,China;Department of Pediatric Hematology&Oncology,the Affiliated Hospital of Qingdao University,Qingdao 266003,China;Department of Hematology,Children′s Hospital,Capital Pediatric Research Institute,Beijing 100020,China;Department of Pediatrics,Second Hospital of Hebei Medical University,Shijiazhuang 050000,China;Department of Pediatrics,Forth Hospital of Hebei Medical Univers

机构地区：[1]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 [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]北京高博博仁医院儿童淋巴瘤科,北京100070 [4]湖南省儿童医院血液内科,长沙410007 [5]国家儿童医学中心复旦大学附属儿科医院血液科,上海201102 [6]郑州儿童医院血液肿瘤科,郑州450018 [7]西安市儿童医院血液肿瘤科,西安710002 [8]上海交通大学附属新华医院小儿血液肿瘤科,上海200092 [9]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 [10]北京大学人民医院儿科,北京100044 [11]安徽省儿童医院血液肿瘤科,合肥230022 [12]青岛大学附属医院儿童医学中心儿童血液肿瘤科,青岛266003 [13]首都儿科研究所附属儿童医院血液内科,北京100020 [14]河北医科大学第二医院儿科,石家庄050000 [15]河北医科大学第四医院儿科,石家庄050011 [16]郑州大学第一附属医院血液/肿瘤科,郑州450052 [17]华中科技大学同济医学院附属武汉市儿童医院血液肿瘤科,武汉430016 [18]华中科技大学同济医学院附属协和医院儿童血液与肿瘤科,武汉430022 [19]郑州大学第三附属医院血液/肿瘤科,郑州450052 [20]温州医科大学附属第二医院儿科,温州325024 [21]山东第一医科大学第一附属医院小儿血液科,济南250022 [22]福建医科大学附属泉州第一医院儿科,泉州362002 [23]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 [24]北京大学第三医院病理科,北京100191 [25]山东大学附属儿童医院(济南市儿童医院)儿科研究所,济南250022

出　　处：《中华儿科杂志》2024年第10期941-948,共8页Chinese Journal of Pediatrics

基　　金：北京市医院管理局儿科学科协同发展中心儿科专项(XTZD20180204);济南市卫生健康委员会科技计划(2023-1-57)

摘　　要：目的分析儿童伯基特淋巴瘤(BL)化疗延迟的影响因素及其对预后的影响。方法回顾性队列研究。收集中国儿童淋巴瘤协作组(CNCL)2017年5月至2022年12月收治的591例年龄≤18岁BL患儿临床资料,治疗均采用CNCL-BL-2017方案。依据临床特征,治疗方案分为A组、B组、C组。根据化疗总时间是否延迟分为化疗延迟组和非化疗延迟组。治疗方案C组患儿根据化疗总延迟时间分为非延迟组、1~7 d化疗延迟组和>7 d化疗延迟组。分析化疗延迟与性别、年龄、化疗前合并肿瘤溶解综合征、骨髓受累、治疗分组、血清乳酸脱氢酶(LDH)>正常4倍、化疗后合并Ⅲ~Ⅳ级骨髓抑制、中期评估有残留、重症感染(包括重症肺炎、败血症、脑膜炎、水痘等)等因素的关系。应用Logistic回归分析影响化疗延迟的因素,采用Kaplan-Meier及Log-Rank检验绘制生存曲线并组间比较。结果591例患儿中男504例、女87例,随访时间34.8(18.6,50.1)个月,3年总生存率(OS)为(92.5±1.1)%,3年无事件生存率(EFS)为(90.5±1.2)%。化疗延迟组73例(12.4%),非化疗延迟组518例(87.6%)。化疗延迟的原因包含重症感染72例(98.6%)、骨髓抑制65例(89.0%)、脏器功能损伤35例(47.9%)、肿瘤溶解综合征22例(30.1%)等。治疗方案B组7例化疗延迟中COPADM(长春新碱+环磷酰胺+泼尼松+柔红霉素+甲氨蝶呤+鞘内注射)阶段4例,CYM(甲氨蝶呤+阿糖胞苷+鞘内注射)阶段3例,治疗方案C组66例化疗延迟常见于COPADM(28例)和CYVE1(小剂量阿糖胞苷+大剂量阿糖胞苷+依托泊苷+甲氨蝶呤,12例)两阶段。多因素Logistic回归分析显示年龄>10岁(OR=0.54,95%CI 0.30~0.93)、化疗前合并肿瘤溶解综合征(OR=0.48,95%CI 0.27~0.84)、化疗后合并Ⅲ~Ⅳ级骨髓抑制(OR=0.55,95%CI 0.33~0.91)为化疗延迟的独立危险因素。化疗延迟组患儿3年OS、EFS均低于非化疗延迟组[(79.4±4.9)%比(94.2±1.1)%,(80.2±4.8)%比(92.0±1.2)%,均P<0.05]。治疗方案C组�ObjectiveTo analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma(BL)and their influence on prognosis.MethodsRetrospective cohort study.Clinical data of 591 children aged≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma(CNCL)was collected.The patients were treated according to the protocol CNCL-BL-2017.According to the clinical characteristics,therapeutic regimen was divided into group A,group B and group C.Based on whether the total chemotherapy time was delayed,patients were divided into two groups:the delayed chemotherapy group and the non-delayed chemotherapy group.Based on the total delayed time of chemotherapy,patients in group C were divided into non-delayed chemotherapy group,1-7 days delayed group and more than 7 days delayed group.Relationships between delayed chemotherapy and gender,age,tumor lysis syndrome before chemotherapy,bone marrow involvement,disease group(B/C group),serum lactate dehydrogenase(LDH)>4 times than normal,gradeⅢ-Ⅳmyelosuppression after chemotherapy,minimal residual disease in the interim assessment,and severe infection(including severe pneumonia,sepsis,meningitis,chickenpox,etc.)were analyzed.Logistic analysis was used to identify the relevant factors.Kaplan-Meier method was used to analyze the patients'survival information.Log-Rank was used for comparison between groups.ResultsAmong 591 patients,504 were males and 87 were females,the follow-up time was 34.8(18.6,50.1)months.The 3-year overall survival(OS)rate was(92.5±1.1)%,and the 3-year event-free survival(EFS)rate was(90.5±1.2)%.Seventy-three(12.4%)patients were in delayed chemotherapy group and 518(87.6%)patients were in non-delayed chemotherapy group.The reasons for chemotherapy delay included 72 cases(98.6%)of severe infection,65 cases(89.0%)of bone marrow suppression,35 cases(47.9%)of organ dysfunction,22 cases(30.1%)of tumor lysis syndrome,etc.There were 7 cases of chemotherapy delay in group B,which were seen in COPADM(vincristine+cyclophosphamide+pred

关 键 词：伯基特淋巴瘤 预后 多中心研究 

分 类 号：R733.1[医药卫生—肿瘤]