免疫靶向联合减毒化疗治疗儿童经典霍奇金淋巴瘤的临床研究  

Clinical study of immune-targeting combined with attenuated chemotherapy in the treatment of children with classic Hodgkin lymphoma

作　　者：高慧霞 李英[2] 李楠[1] 黄爽[1] 张梦[1] 周春菊[3] 张宁宁[4] 张伊明 杨菁[1] 金玲[1] 王晓玲[2] 王天有[5] 段彦龙[1] Gao Huixia;Li Ying;Li Nan;Huang Shuang;Zhang Meng;Zhou Chunju;Zhang Ningning;Zhang Yiming;Yang Jing;Jin Ling;Wang Xiaoling;Wang Tianyou;Duan Yanlong(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,National Key Clinical Discipline of Pediatric Oncology,Key Laboratory of Major Diseases in Children,Ministry of Education,Beijing 100045,China;Department of Fharmacy,Beijing Children′s Hospital,Capital Medical University,Beijing 100045,China;Department of Pathology,Beijing Children′s Hospital,Capital Medical University,Beijing 100045,China;Department of Imaging,Beijing Children′s Hospital,Capital Medical University,Beijing 100045,China;Hematology Center,Beijing Children's Hospital,Capital Medical University,National Center for Children's Health,National Key Clinical Discipline of Pediatric Hematology,National Key Discipline of Pediatrics(Capital Medical University),Key Laboratory of Major Diseases in Children,Ministry of Education,Beijing 100045,China)

机构地区：[1]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、儿童肿瘤国家临床重点专科、儿科重大疾病研究教育部重点实验室,北京100045 [2]首都医科大学附属北京儿童医院药学部,北京100045 [3]首都医科大学附属北京儿童医院病理科,北京100045 [4]首都医科大学附属北京儿童医院影像科,北京100045 [5]国家儿童医学中心、首都医科大学附属北京儿童医院血液病中心、儿童血液病国家临床重点专科、儿科学国家重点学科、儿科重大疾病研究教育部重点实验室,北京100045

出　　处：《中华儿科杂志》2024年第11期1097-1102,共6页Chinese Journal of Pediatrics

摘　　要：目的探讨维布妥昔单抗(BV)联合利妥昔单抗及减毒化疗治疗儿童经典霍奇金淋巴瘤(cHL)的安全性和临床效果。方法前瞻性、非随机、风险分配的临床研究。收集2022年10月至2024年5月在首都医科大学附属北京儿童医院初诊并完成治疗的28例中、高危cHL患儿的临床资料[包括年龄、性别、B症状、有无巨大瘤灶、肿瘤CD30及Epstein-Barr病毒编码RNA(EBER)表达、临床分期、危险度分层等],基于危险度分层及早期治疗反应,予免疫靶向联合减毒化疗。随访至2024年5月1日,记录用药期间有无输注反应及用药后的不良反应。结果28例患儿中男22例,女6例;年龄为12(5,16)岁;16例(57%)患儿伴有巨大瘤灶,10例(36%)患儿有B症状;病理分型以结节硬化型(14例,50%)最常见;Ann Arbor分期:Ⅱ期7例,Ⅲ期14例,Ⅳ期7例;危险度分组:中危组5例,高危组23例;EBER阳性20例(71%),阴性6例(21%),所有入组患儿肿瘤细胞均表达CD30抗原。化学免疫治疗疗程包括4个疗程5例(18%),6个疗程21例(75%),8个疗程2例(7%);25例(89%)患儿2个疗程化疗后早期评估获得代谢学完全缓解(CMR);治疗结束后,中危组CMR率为100%;高危组CMR率为87%(20/23);最终4例(14%)接受残留野放疗。治疗不良反应包括Ⅰ~Ⅱ级骨髓抑制、早期输液反应和轻度周围神经病变,仅1例次患儿发生3级以上的不良事件,均未影响序贯治疗。化疗结束及随访3个月时患儿IgA、IgG、IgM均较化疗前基线水平下降,总B细胞计数治疗早期(2个疗程后)即开始低于化疗前水平,治疗期间监测总B细胞计数为50(0,101)×10^(6)/L,治疗结束时为12(0,25)×10^(6)/L;随访时间6(3,13)个月,28例患儿均无事件生存,截至末次随访所有患儿持续完全反应。随访至6和9个月时,患儿IgA、IgG、IgM及总B细胞计数分别恢复至化疗前基线水平。结论BV联合利妥昔单抗减毒化疗治疗儿童cHL早期结果总体良好,安全性可靠,可显著降低放射治�ObjectiveTo evaluate the efficacy and safety of brentuximab vedotin(BV)combined with rituximab and attenuated chemotherapy in the treatment of children with classic Hodgkin lymphoma(cHL).MethodsA prospective,non-randomized,risk-assigned study.Clinical data(including age,gender,B symptoms,bulky disease,CD30 and Epstein-Barr virus-encoded RNA(EBER)expression,clinical stage,risk stratification,etc.)of 28 intermediate to high-risk cHL children diagnosed and treated at Beijing Children′s Hospital Affiliated to Capital Medical University from October 2022 to May 2024 were collected.Immuno-targeted combined with attenuated chemotherapy was administered based on risk stratification and early treatment response.The patients were followed up until May 1st,2024.The infusion reactions and adverse reactions after treatment were recorded.ResultsIn all 28 patients,there were 22 males and 6 females,the age was 12(5,16)years,16 cases(57%)presented with bulky disease and 10 cases(36%)with B symptoms.The most common pathological type was nodular sclerosis(14 cases,50%).There were 7 cases of stageⅡ,14 cases of stageⅢand 7 cases of stageⅣaccording to the Ann Arbor staging system.There were 5 cases in the intermediate-risk group and 23 cases in the high-risk group.EBER was positive in 20 cases(71%)and negative in 6 cases(21%),and CD30 antigen was expressed in tumor cells of all enrolled children.Treatment duration:5 cases(18%)received 4 courses of treatment,21 cases(75%)received 6 courses of treatment,and 2 cases(7%)received 8 courses of treatment,25 cases(89%)achieved complete metabolism response(CMR)through early assessment after 2 courses of chemotherapy.The CMR rates were 100%in intermediate-risk group and 87%(20/23)in high-risk group,respectively.Four patients(14%)finally received residual field radiotherapy.Toxicities included gradeⅠ-Ⅱmyelosuppression,early infusion reaction and mild peripheral neuropathy,only one case of grade 3 adverse events was recorded and did not affect sequential treatment.At the end of treatm

关 键 词：淋巴瘤 儿童 治疗 临床研究性 

分 类 号：R733.1[医药卫生—肿瘤]