伴骨髓转移的神经母细胞瘤患儿初诊时骨髓染色体核型的临床意义

目的总结伴骨髓转移的神经母细胞瘤(NB)患儿初诊时骨髓染色体核型分析结果,探讨其临床意义。方法采用G显带的方法,对2015年1月至2017年12月北京儿童医院血液肿瘤中心收治的伴骨髓转移的NB患儿进行染色体核型分析,总结临床特点、分析预后,随访至2018年12月31日。结果1.共120例患儿,男74例,女46例,≥18个月者98例(81.7%)。染色体正常组60例,其中56例(93.3%)国际神经母细胞瘤分期系统(INSS)-Ⅳ期,余4例为INSS-Ⅳs期;低危(LR)2例,中危(MR)9例,高危(HR)49例(81.7%);7例患儿MYCN基因扩增。染色体异常组60例患儿均为INSS-Ⅳ期,MR 1例,余59例(98.3%)均为HR,14例MYCN基因扩增。2.染色体异常患儿60例中单纯数目异常和结构异常者分别为4例、14例,42例患儿同时合并染色体数目及结构异常。数目异常方面,21号、10号、11号染色体缺失最为常见;结构异常方面涉及11q、1p、3p区段的异常发生率高。3.染色体正常组患儿随访时间为4~44个月,17例出现肿瘤进展或复发;染色体异常组患儿随访时间2~42个月,其中31例出现肿瘤进展或复发。所有患儿3年累积总生存率和累积无事件生存率分别为60.0%、48.4%;染色体正常组患儿3年累积生存率为74.2%,3年累积无事件生存率为65.7%;染色体异常组患儿3年累积生存率为47.5%,3年累积无事件生存率为24.9%;出现进展或复发患儿染色体数目异常以10号染色体缺失常见,结构异常以11q、1p、2p区域较多。结论NB患儿肿瘤细胞染色体异常率高,但重复率低,个体间差异明显。10号染色体缺失、11q、1p、2p区域结构异常可能为提示NB预后不良因素;通过骨髓标本进行肿瘤染色体核型分析可行,可为更精准的危险度分层和治疗提供依据。

Chromosome karyotype of bone marrow and its clinical significance in the first diagnosis of neuroblastoma with bone marrow metastasis

Objective To summarize and analyze the results of chromosome karyotype in children with neuroblastoma(NB)with bone marrow metastasis at first diagnosis,and to discuss the clinical significance.Methods G-banding was applied to the analysis of chromosome karyotype of patients who were regularly treated in the Hematological and Oncology Center in Beijing Children′s Hospital from January 2015 to December 2017,and all the patients were followed up until December 31,2018.Their clinical features and prognosis were analyzed.Results(1)There were 120 cases with bone marrow metastasis,including 74 boys and 46 girls,and 98 cases(81.7%)were≥18 months.Among 60 cases with normal chromosome,56 cases(93.3%)were in International Neuroblastoma Staging System(INSS)-Ⅳphase,and 4 cases in INSS-Ⅳs phase;there were 2 low-risk(LR)cases,9 intermediate-risk(MR)cases,and 49 high-risk(HR)cases(81.7%);7 cases had MYCN gene amplifications.All 60 patients with chromosome abnormalities were in INSS-Ⅳphase;there was 1 case in MR and 59 cases(98.3%)in HR;14 cases had MYCN gene amplifications.(2)Among 60 children(50%)with chromosome abnormalities,4 children had number abnormalities,14 children had structural abnormalities,and 42 children had both number and structural chromosome abnormalities.Chromosome 21,10,11 deletions were the most common in number abnormalities;structural abnormalities involving 11q,1p,3p segments had a high incidence.(3)Seventeen cases of children with normal chromosome had tumor progression or recurrence during the 4 to 44-month follow-up period,and 31 cases of children with chromosome abnormalities had tumor progression or recurrence during the 2 to 42-month follow-up period.The 3-year overall survival rate and event-free survival rate of all children were 60.0%and 48.4%,respectively;children in the normal chromosome group had a 3-year overall survival rate of 74.2%and an event-free survival rate of 65.7%;the 3-year overall survival rate and event-free survival rate of children with chromosome abnormalities were 47.5%and 24.9%,respectively.Most children suffering from tumor progression or recurrence had chromosome 10 deletion,and abnormal structure of 11q,1p,2p segments.Conclusion The chromosomal abnormality rate of Nb children's tumor cells is high,but the repetition rate is low,and the individual difference is obvious.The deletion of chromosome 10,abnormal regional structure of 11q,1p and 2p segments may be poor prognostic factors for NB.Chromosome karyotype analysis of bone marrow samples is feasible,which can provide a basis for more accurate risk stratification and treatment.