高超二倍体核型儿童急性淋巴细胞白血病的临床特征及预后——福建省多中心回顾性研究

Clinical features and prognosis of high hyperdiploid childhood acute lymphoblastic leukemia:a multicenter retrospective analysis in Fujian Province,China

目的探讨儿童高超二倍体(high hyperdiploid,HHD)急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)的临床特征及预后。方法回顾性分析2011年4月—2020年12月福建省5家医院收治的1414例ALL初诊患儿的临床资料。根据染色体核型,分为伴HHD组(172例)和不伴HHD组(1242例),比较两组的临床特征及疗效,并进一步探讨HHD ALL的预后影响因素。结果在1414例ALL初诊患儿中,172例(12.16%)检出HHD。伴HHD组初诊有不良预后危险因素(起病年龄≥10岁或<1岁、初诊白细胞计数≥50×109/L、T细胞表型)、常见融合基因(TEL-AML1、BCR-ABL1、E2A-PBX1、MLL基因重排)阳性的患儿比例均低于不伴HHD组(均P<0.05),而诱导化疗后微小残留病(minimal residual disease,MRD)<0.01%的患儿比例高于不伴HHD组(P<0.05)。伴HHD组预期10年无事件生存(event-free survival,EFS)率及总生存率均高于不伴HHD组(P<0.05)。单因素分析显示,染色体数目58~66、10号染色体三体、17号染色体三体、诱导化疗第15天或第19天骨髓MRD<1%、诱导化疗第33天或第46天骨髓MRD<0.01%是高EFS率的影响因素(均P<0.05);10号染色体三体与高总生存率有关(P<0.05)。Cox比例风险回归模型分析显示,17号染色体三体与高EFS率密切相关(P<0.05)。结论儿童HHD ALL初诊时不良预后危险因素较少,总体预后佳;染色体数目及特定染色体三体与预后相关。

Objective To study the clinical features and prognosis of high hyperdiploid(HHD)childhood acute lymphoblastic leukemia(ALL).Methods A retrospective analysis was performed on the medical data of 1414 children who were newly diagnosed with ALL and were admitted to five hospitals in Fujian Province of China from April 2011 to December 2020.According to karyotype,they were divided into two groups:HHD(n=172)and non-HHD(n=1242).The clinical features and treatment outcome were compared between the two groups,and the factors influencing the prognosis were further explored.Results Among the 1414 children with ALL,172(12.16%)had HHD.Compared with the non-HHD group,the HHD group had significantly lower proportions of children with risk factors for poor prognosis at diagnosis(age of onset≥10 years or<1 year,white blood cell count≥50×109/L,and T-cell phenotype)or positive fusion genes(TEL-AML1,BCR-ABL1,E2A-PBX1,and MLL gene rearrangement)(P<0.05).The HHD group had a significantly higher proportion of children with minimal residual disease(MRD)<0.01%at the end of induction chemotherapy(P<0.05).The 10-year event-free survival(EFS)rate and overall survival(OS)rate in the HHD group were significantly higher than those in the non-HHD group(P<0.05).The univariate analysis showed that the number of chromosomes of 58-66,trisomy of chromosome 10,trisomy of chromosome 17,bone marrow MRD<1%on day 15 or 19 of induction chemotherapy,and bone marrow MRD<0.01%on day 33 or 46 of induction chemotherapy were associated with a higher EFS rate(P<0.05),and trisomy of chromosome 10 was associated with a higher OS rate(P<0.05).The multivariate Cox analysis showed that trisomy of chromosome 17 was closely associated with a high EFS rate(P<0.05).Conclusions The ALL children with HHD have few risk factors for poor prognosis at diagnosis and often have good prognosis.The number of chromosomes and trisomy of specific chromosomes are associated with prognosis in these children.