TEL-AML1融合基因阳性儿童急性B淋巴细胞白血病临床特点及预后分析

Clinical characteristics and prognosis analysis of childhood B-cell acute lymphoblastic leukemia with TEL-AML1 fusion gene positive

目的探讨TEL-AML1融合基因阳性的儿童急性B淋巴细胞白血病(B-ALL)的临床特点及预后。方法对山西省儿童医院血液科2013年1月至2018年6月收治的55例TEL-AML1融合基因阳性初诊B-ALL患儿的临床特点、治疗效果及预后因素进行回顾性分析,采用Kaplan-Meier法评估患儿3年无事件生存(EFS)率和总生存(OS)率,Cox回归模型评估EFS、OS的影响因素。结果55例患儿TEL-AML1融合基因均阳性,且未合并其他融合基因阳性。≥10岁者4例(7.3%)。初诊时肝大33例(60.0%),脾大28例(50.9%),全身浅表淋巴结肿大27例(49.1%),白细胞计数≥50×10^9/L 5例(9.1%),染色体异常19例(34.6%)。55例患儿经形态学、免疫学、细胞遗传学、分子生物学(MICM)分型及调整危险度后,低危、中危、高危分别为36例(65.5%)、18例(32.7%)、1例(1.8%)。经规律化疗,第15天达完全缓解(CR)50例,1个疗程CR率100.0%(55/55)。第33天微小残留病(MRD)<10-443例(78.2%),MRD≥10^-4且<10-212例(21.8%),第12周MRD≥10^-3 1例(1.8%)。3~6个月融合基因转阴率达61.8%(34/55)。死亡3例(5.5%),其中1例(1.8%)患儿死于复发,复发距离初诊时间27个月;另2例(3.6%)均死于化疗期间感染。55例患儿3年EFS率、3年OS率分别为90.3%、93.2%。低危组3年EFS率、3年OS率均为100.0%;中危组3年EFS率、3年OS率分别为78.7%、86.6%;高危组1例死亡,3年EFS率、3年OS率均为0。低危组3年EFS率、3年OS率均高于中危组,差异均有统计学意义(均P<0.05)。第12周MRD<10^-3和≥10^-3患儿的3年EFS率分别为92.0%、0;3年OS率分别为95.0%、0,差异均有统计学意义(P<0.05)。Cox多因素回归分析显示,第12周MRD是影响患儿EFS、OS的独立危险因素(OR=2.971,95%CI 1.330~6.633,P=0.008;OR=2.884,95%CI 1.295~6.419,P=0.009)。结论TEL-AML1融合基因阳性的B-ALL患儿复发率低,生存率高,预后良好。危险度分层、第12周MRD均是影响患儿预后的因素。

Objective To investigate the clinical characteristics and prognosis of children B-cell acute lymphoblastic leukemia(B-ALL)with TEL-AML1 fusion gene positive.Methods Clinical characteristics,therapeutic effects and prognostic factors of 55 children B-ALL patients with TEL-AML1 fusion gene positive in Children's Hospital of Shanxi from January 2013 to June 2018 were retrospectively analyzed.Kaplan-Meier method was used to evaluate 3-year event-free survival(EFS)rate and overall survival(OS)rate.Influencing factors of EFS and OS were evaluated by using Cox regression analysis.Results TEL-AML1 fusion gene was positive in all 55 children,and no other fusion gene positive was merged.There were 4 patients(7.3%)≥10 years old.At initial diagnosis,33 patients(60.0%)had hepatomegaly,28 patients(50.9%)had splenomegaly,and 27 patients(49.1%)had superficial lymphadenectasis.There were 5 patients(9.1%)with white blood cell count≥50×10^9/L,and 19 patients(34.6%)had abnormalities of chromosome.All the 55 children were divided into the low risk group[36 cases(65.5%)],the intermediate risk group[18 cases(32.7%)],high risk group[1 case(1.8%)]according to Morphology,Immunology,Cytogenetics and Molecular Biology(MICM)and adjusted risk.After regular treatments,50 patients achieved complete remission(CR)on the 15th day.The CR rate after one-course of induction therapy was 100.0%.On the 33rd day,43 patients(78.2%)had minimal residual disease(MRD)<10-4,12 patients(21.8%)had MRD≥10^-4 and MRD<10^-2,1 patient(1.8%)had MRD≥10^-3 at the 12th week.During three to six months,the negative rate of fusion gene was 61.8%(34/55).There were 3 deaths(5.5%),and one(1.8%)of them died of recurrence,and the recurrence time was 27 months from the initial diagnosis;the other 2 cases(3.6%)died of infection during chemotherapy.In 55 patients,the 3-year EFS rate and OS rate was 90.3%and 93.2%,respectively.The 3-year EFS rate and OS rate in the low risk group was 100.0%both;the 3-year EFS rate and OS rate in the intermediate risk group was 78.7%and 86.6%,respectively;the 3-year EFS rate and OS rate in the high risk group was 0 both and one died.EFS rate and OS rate in low risk group were higher than those in the intermediate risk group,and the differences were statistically significant(P<0.05).The EFS rate was 92.0%and 0 at the 12th week MRD<10-3 group and MRD≥10^-3 group,and OS rate was 95.0%and 0 at the 12th week MRD<10-3 group and MRD≥10^-3 group(P<0.05).Cox multivariate analysis showed that MRD at the 12th week was an independent risk factor influencing EFS and OS(OR=2.971,95%CI 1.330-6.633,P=0.008;OR=2.884,95%CI 1.295-6.419,P=0.009).Conclusions Children B-ALL patients with TEL-AML1 fusion gene positive have a low recurrence rate,high survival rate and good prognosis.Risk stratification and the 12th week MRD are the influencing factors of the prognosis.