MLL基因重排阳性儿童急性淋巴细胞白血病患者临床特征及预后分析

Clinical Characteristics and Prognosis of MLL Rearranged Child-hood Acute Lymphocyte Leukemia

目的:探讨MLL基因重排(MLL-r)阳性儿童急性淋巴细胞白血病(ALL)的临床特征及预后因素。方法:回顾性分析2011年4月至2020年12月福建省5家医院收治的1414例初诊ALL患儿的临床资料。比较MLL-r^(+)与MLL-r-ALL组患儿的临床特征及疗效,采用COX回归模型分析影响MLL-r ALL预后的因素。结果:在所有纳入的ALL患儿中,年龄<1岁患儿占所有入组ALL的比例为1.8%,MLL-r^(+)检出率为3.4%(48/1414);在<1岁、≥1岁且≤14岁年龄组中,MLL-r检出率分别为38.5%(10/26)和2.7%(38/1388),差异有统计学意义(P=0.000)。与MLL-r-组相比,MLL-r^(+)组初诊年龄<1岁、白细胞数(WBC)≥50×10^(9)/L、合并中枢神经系统白血病(CNSL)及睾丸白血病(TL)的患者比例更高,而诱导治疗后d 33或d 46微小残留病(MRD)<0.01%的患者比例更低(P<0.05)。MLL-r^(+)组预期10年无事件生存(EFS)率及总体生存(OS)率均显著低于MLL-r-组(EFS:49.9%vs 77.0%;OS:55.3%vs 82.9%,P<0.05)。COX分析结果显示,初诊年龄<1岁、诱导治疗后d 33或d 46 MRD≥0.01%为MLL-r^(+)ALL更差OS及EFS的独立危险因素(P<0.05)。结论:MLL-r^(+)ALL患儿初诊年龄<1岁、高WBC数、合并CNSL和TL更常见,且早期治疗反应较差,预后不良;初诊年龄<1岁、诱导治疗后MRD阳性可能为预后不良的危险因素。

Objective:To investigate the clinical characteristics and prognostic factors in childhood acute lymphoblastic leukemia with MLL gene-rearrangement-positive(MLL-r^(+)ALL).Methods:The clinical data of 1414 newly diagnosed children with ALL admitted to five hospital in Fujian province from April 2011 to December 2020 were retrospectively analyzed.The clinical characteristics and efficacy of MLL-r^(+)and MLL-r~subgroup were compared.The prognostic factors of MLL-r ALL were analyzed by COX regression model.Results:Among all children with ALL,the proportion of patients aged less than 1 year old was 1.8%,and the detection rate of MLL-r^(+)was 3.4%(48/1414).The positive detection rate of MLL-r in the age groups<1 year old,and≥1 year old and≤14 years old was 38.5%(10/26)and 2.7(38/1388),respectively,the difference was statistically significant(P<0.000).Compared with MLL-r~group,the MLL-r^(+)group had a higher proportion of patients with age<1 year,white blood cell(WBC)count≥50x 109/L,combined central nervous system leukemia(CNSL)and testicular leukemia(TL),while MRD<0.01%on d 33 or d 46 of induction chemotherapy was lower(all P<0.05).The expected 10-year event free survival(EFS)rate and overall survival(OS)rate of the MLL-r^(+)group were significantly lower than those of the MLL-r~group(EFS:49.9%vs 77.0%;OS:55.3%vs 82.9%,P<0.05).COX regression model analysis showed that age<1 year,minimal residual disease(MRD)≥0.01%ond33 or d 46 of induction chemotherapy were independent risk factors for worse OS and EFS in MLLr^(+)ALL patients(all P<0.05).Conclusion:Age<1 year old,high WBC,concomitant CNSL and TL are more common in children with MIL-r^(+)ALL at initial diagnosis,with poor early treatment response and long-term prognosis.Age<1 year old at initial diagnosis and MRD positive after induction chemotherapy may be risk factors for poor prognosis.