摘要
目的分析和总结儿童横纹肌肉瘤(RMS)常用化疗药物基因组DNA检测结果,分析化疗药物不良反应与药物基因组DNA多态性的关系,为指导治疗提供依据。方法回顾性分析2017年1月至2018年6月首都医科大学附属北京儿童医院血液肿瘤中心收治的RMS患儿。入组标准为确诊RMS,在首都医科大学附属北京儿童医院血液肿瘤中心规律诊治、随访的患儿;应用外周血DNA荧光杂交序列测定几种常用化疗药物基因组DNA。化疗药物不良反应按国立癌症研究所常规毒性判定标准(NCI-CTCAE 4.0版)。总结初诊时原发瘤灶和转移瘤灶部位、大小、国际横纹肌肉瘤临床分期(TNM-UICC)、国际横纹肌肉瘤研究组(IRS)临床分期、危险度分组、病理类型,化疗后主要脏器功能变化及治疗,分析不良反应与药物基因组DNA多态性的关系。采用SPSS 22.0软件进行χ^2检验。结果共32例患儿入组,男20例,女12例;中位年龄50个月(15~120个月)。胸、腹、盆腔9例,头颈部(非脑膜旁)8例,膀胱前列腺7例,四肢、躯干3例,脑膜旁区2例,泌尿生殖道(非膀胱前列腺)1例,其他部位2例。胚胎型17例,腺泡型15例。TNM临床分期1期5例,2期5例,3期10例,4期12例;IRS术后病理分期Ⅲ期21例,Ⅳ期11例。中危22例,高危10例。32例患儿行UGT1A1*6基因检测,GG型18例(56.3%)、GA型13例(40.6%)、AA型1例(3.1%)。27例患儿行ABCB1基因监测,CT型14例(51.9%)、TT型13例(48.1%);29例患儿行GSTP1基因检测,GA型7例(24.1%)、GG型2例(5.6%)、AA型19例(59.7%)、AG型1例(2.8%);30例患儿行CYP3A5基因检测,GA型2例(5.6%)、GG型13例(43.3%)、AG型15例(50.0%)。患儿均按BCH-RMS-2007方案以VAC(长春新碱、阿霉素、环磷酰胺)为基础规律化疗,2017年起以VAC和VI(长春新碱、伊立替康)为基础化疗。化疗前手术9例,化疗后手术10例,二次手术5例。化疗第12周行局部放疗,伴中枢神经系统侵犯者第1周进行放疗。血液毒性以中性粒细胞减少为主,3级2例,4级30例。丙氨酸转氨酶升高2级6例,3级3例。自2016年起应用伊立替康32例,中性粒细胞减少3级2例、4级30例,腹泻1级4例、2级3例、3级5例、4级3例。腹泻严重程度与UGT1A1*6基因型多态性差异有统计学意义(P<0.05)。结论儿童RMS常用化疗药物安全性高。若化疗药物基因组DNA基因型检测提示为慢代谢型,化疗剂量应减量,并动态监测化疗药物不良反应。
Objective To analyze and summarize the results of genomic DNA test findings of chemotherapeutic drugs commonly used in pediatric rhabdomyosarcoma(RMS)in children,and to analyze the relationship between adverse reactions to chemotherapy toxicity and genomic DNA polymorphisms,so as to provide evidence for guiding treatment.Methods Retrospective analysis was conducted in RMS children admitted at Hematology Oncology Center,Beijing Children′s Hospital,Capital Medical University from January 2017 to June 2018.The criteria for enrollment were definite diagnosis of RMS,regular treatment and follow-up at Hematology Oncology Center,Beijing Children′s Hospital,Capital Medical University,and detection of peripheral blood DNA fluorescence hybridization sequence for several commonly chemotherapy drugs.The toxicity of chemotherapeutic drugs was detected based on the National Cancer Institute routine toxicity criteria(NCI-CTCAE version 4.0).Summary and analysis indicators included primary and metastatic site,size,international RMS clinical stage(TNM-UICC),Intergroup Rhabdomyosarcoma Study(IRS)Clinical Grouping Classification,risk grouping,pathological type,changes in major organ functions,as well as processes of surgery,chemotherapy and radiotherapy,and the association between toxicity and DNA polymorphism of drug genes was analyzed.SPSS 22.0 software was used forχ^2 test.Results A total of 32 children were enrolled,and 20 cases were male and 12 cases were female,their median age was 50 months(15-120 months).The primary tumor of 9 cases were sited in the chest,abdomen and basin,8 cases in the head and neck(non-meningeal),7 cases in bladder prostate,3 cases in limbs,2 cases in the meningeal area,1 case in urogenital tract(non-bladder prostate),2 cases in other parts.Seventeen cases were embryonic type and 15 cases were alveolar type.Five cases were TNM-Ⅰstage,5 cases were TNM-Ⅱstage,10 cases TNM-Ⅲstage,12 cases were TNM-Ⅳstage,21 cases were IRS-Ⅲ,11 cases were IRS-Ⅳ.Twenty-two cases were moderate-risk(MR),10 cases were high-risk(HR).Twenty-two cases were detected UGT1A1*6 gene,18 cases in GG type,13 cases in GA type,and 1 case in AA type.ABCB1 gene monitoring was performed in 27 children,14 cases of CT type and 13 cases of TT type;29 cases were detected GSTP1 gene,7 cases of GA type and 2 cases of GG type,19 cases of AA type,1 case of AG type;30 cases were detected CYP3A5 gene,2 cases of GA type,13 cases of GG type,AG 15 cases.All patients were treated according to the BCH-RMS-2007 protocol using VAC(Vincristine,Doxorubicin,and Cyclophosphamide)as the basis for chemotherapy.From 2017,VAC and VI regimen(Vincristine,Irinotecan)were defined as the standard of backbone chemotherapeutic regimen for MR.Nine cases underwent surgery before chemotherapy and 10 cases had surgery after chemotherapy,among them,5 cases underwent twice operation.Local radiotherapy was performed on the 12th week of chemotherapy,and the central nervous system involvement cases started in the first week.Hematological toxicity was mainly caused by neutropenia,with 2 cases of grade 3 and 30 cases of grade 4.Liver function damage of grade 2 was 6 cases,grade 3 was 3 cases.Four patients with grade 1 diarrhea,3 patients with grade 2,5 patients with grade 3,3 patients with grade 4.There was significant diffe-rence between the severity of diarrhea and UGT1A1*6 genotype polymorphism(P<0.05).Conclusions Chemothe-rapy for RMS patients is highly safety.If the genomic DNA test of chemotherapy drugs show a slow metabolism type,the dose of chemotherapy should be reduced,and the toxicity of chemotherapy drugs should be monitored dynamically.
作者
柴希
刘亦伟
金眉
苏雁
赵文
赵倩
王生才
何乐健
秦红
王焕民
张潍平
孙宁
王晓玲
马晓莉
Chai Xi;Liu Yiwei;Jin Mei;Su Yan;Zhao Wen;Zhao Qian;Wang Shengcai;He Lejian;Qin Hong;Wang Huanmin;Zhang Weiping;Sun Ning;Wang Xiaoling;Ma Xiaoli(Beijing Key Laboratory of Pediatric Hematology Oncology,National Key Discipline of Pediatrics(Capital Medical University),Key Laboratory of Major Diseases in Children,Ministry of Education,Hematology Oncology Center,Beijing Children′s Hospital,Capital Medical University,National Center for Children′s Health,Beijing 100045,China;Clinical Research Center,Beijing Children′s Hospital,Capital Medical University,National Center for Children′s Health,Beijing 100045,China;Department of Otorhinolaryngology Head and Neck Surgery,Beijing Children′s Hospital,Capital Medical University,National Center for Children′s Health,Beijing 100045,China;Department of Oncology Surgery,Beijing Children′s Hospital,Capital Medical University,National Center for Children′s Health,Beijing 100045,China;Department of Urological Surgery,Beijing Children′s Hospital,Capital Medical University,National Center for Children′s Health,Beijing 100045,China)
出处
《中华实用儿科临床杂志》
CSCD
北大核心
2019年第21期1635-1639,共5页
Chinese Journal of Applied Clinical Pediatrics
