TEL/AML1融合基因儿童急性白血病的临床特点与预后

The clinical characteristics and prognosis of childhood acute leukemia with TEL/AML1 fusion gene positive

目的通过对71例TEL/AML1阳性的儿童急性白血病患儿行回顾性分析,明确该融合基因阳性白血病的临床特点,并评估其预后关系。方法2015年11月至2023年7月上海市儿童医院单中心71例TEL/AML1融合基因阳性的急性白血病患儿,男36例,女35例,年龄2~15岁,所有患儿均进行MICM的诊断,除形态、免疫分型和细胞遗传学外,均应用实时荧光探针PCR法进行56种融合基因筛选,并同步予FISH的方法行TEL/AML1探针检测。结果71例患儿PCR法和FISH结果均显示TEL/AML1融合基因阳性,符合率100%。71例患儿中位生存时间为54个月,其中持续缓解59例,放弃6例,死亡2例,复发4例,5年无事件生存率(EFS)是83.2%,5年累积复发率为5.6%。其中2例复发后放弃,另外2例复发患儿经过Car-T和造血干细胞移植后持续缓解至今。有1例患儿停药5年后复发,尽管加强化疗和移植,仍未改善预后,最后死亡;另外1例因高白细胞血症,在诱导缓解期间因感染而死亡。除放弃的6例外,将其他65例分为缓解组(59/65)和非缓解组(6/65),通过对两组多因素分析发现年龄≥6岁,危险分层以及D19d MRD≥0.1%是影响预后的危险因素。结论TEL/AML1融合基因阳性的急性白血病患儿可以获得较高的缓解率,常规化疗就可让其预后较好,诱导缓解后的MRD水平等可为后续治疗方案调整提供依据,复发后应用Car-T联合造血干细胞移植有望进一步改善其预后。

Objective To evaluate the clinical characteristics and prognosis of 71 cases with acute lymphoblastic leukemia(ALL)for positive TEL/AML1 fusion gene through a retrospective analysis.Methods From November 2015 to July 2023,71 children with TEL/AML1 fusion gene positive acute leukemia,including 36 males and 35 females,aged between 2 and 15 years old,were diagnosed with MICM in a single center of Shanghai Children's Hospital.All patients were diagnosed not only using morphology,immunophenotyping,and cytogenetics,but also real-time fluorescence probe PCR was used for screening of 56 fusion genes.FISH was simultaneously performed using TEL/AML1 probes.Results The results of PCR and FISH showed that the TEL/AML1 fusion gene was positive in 71 cases,with a coincidence rate of 100%.The median survival time of 71 patients was 54 months,of which 59 cases had sustained remission,6 abandoned treatment,2 deceased,and 4 relapsed.The 5-year event-free survival(EFS)rate was 83.2%,and the 5-year cumulative recurrence rate was 5.6%.Among the four relapsed cases,two relapsed and gave up,and the other two relapsed children continued to be in remission after Car-T and hematopoietic stem cell transplantation.One patient relapsed after 5 years off drug therapy and eventually died despite intensified chemotherapy and transplantation;The other case died from infection during induction phase of remission due to hyperleukaemia.Excluding the 6 abanndoned cases,the remaining 65 cases were divided into remission group(59/65)and non-remission group(6/65).Through multivariate analysis of the two groups,it was found that age≥6 years old,risk stratification and D19d MRD≥0.1%were adverse factors affecting prognosis.Conclusion Children with acute leukemia with positive TEL/AML1 fusion gene can achieve a higher remission rate,and conventional chemotherapy can improve their prognosis.The MRD level after induction remission can be used as a basis for subsequent treatment,and Car-T therapy combined with hematopoietic stem cell transplantation is expected to further improve their prognosis after relapse.