SIL-TAL1融合基因阳性的儿童急性T淋巴细胞白血病的临床特征及其治疗研究

Clinical Characteristics and Treatment Efficacy of Children with SIL/TAL1 Positive T-Cell Acute Lymphoblastic Leukemia

目的:探讨SIL-TAL1融合基因阳性儿童急性T淋巴细胞白血病(T-cell acute lymphoblastic leukemia,TALL)的临床特征、治疗方案及预后。方法:收集2005年4月至2012年11月间来我院治疗的101例T-ALL患儿的临床资料,比较SIL-TAL1阳性和SIL-TAL1阴性患儿的常见临床特征、早期治疗反应、微小残留病(minimal residual disease,M RD)、无事件生存率(event free survival,EFS)、无复发生存率(relapse free survival,RFS)及SIL-TAL1阳性T-ALL采用BCH-2003方案和CCLG-2008方案治疗的疗效。结果:在101例患儿中共22例携带SIL-TAL1融合基因(21.9%)。SIL-TAL1阳性(22例)和阴性患儿(79例)初诊时性别、年龄、对泼尼松反应及中枢神经系统累及均无明显差异,但SIL-TAL1阳性患儿初诊时外周血白细胞水平明显高于SIL-TAL1阴性患儿(P=0.009)。两组患儿在诱导缓解治疗后、延迟强化治疗Ⅱ前、维持治疗前的MRD水平无明显差异,但SIL-TAL1阳性患儿中巩固治疗前的MRD高水平者明显多于SIL-TAL1阴性患儿(P<0.05),延迟强化治疗I前的MRD高水平者似有增多的趋势(P>0.05)。两组患儿的5年EFS和RFS没有明显差异。将22例SIL-TAL1阳性患儿按CCLG-2008方案的分型标准重新划分危险度,BCH-2003组(10例)的危险度明显高于CCLG-2008组(12例,P=0.029),但两组患儿在常见临床特征、早期治疗反应、MRD水平、长期预后等方面均无明显差异。结论:SIL-TAL1阳性患儿初诊时外周血白细胞水平较高,临床疗效与SIL-TAL1阴性患儿没有显著差异。同时,SIL-TAL1阳性患儿对早期强化治疗可能反应性较差,BCH-2003方案可能更适于这一亚型的患儿。

Objective: To investigate the clinical features,treatment and prognosis of children w ith SIL-TAL1 fusion gene positive T-cell acute lymphoblastic leukemia( T-ALL). Methods: The data of 101 children w ith T-ALL w ere collected from April 2005 to November 2012 in Beijing Children' s Hospital. The common clinical features,early treatment response,minimal residual disease( MRD),event-free survival( EFS) and relapse-free survival( RFS) w ere compared betw een children w ith SIL-TAL1 positive and negative T-ALL. The treatment efficacy in children w ith SILTAL1 positive T-ALL w as compared betw een BCH-2003 and CCLG-2008 protocol. Results: Out of 101 cases,22 cases( 21. 9%) of T-ALL carried SIL-TAL1 fusion gene. The distribution of sex,age,response to prednisone and central nervous system( CNS) involvement w ere no significant different at diagnosis betw een SIL-TAL1 positive and negetive patients. How ever,the WBC count in SIL-TAL1 positive cases w ere significantly higher than that of SIL-TAL1 negative cases at diagnosis( P < 0. 05). Additionally,MRD levels w ere not significantly different betw een children w ith SIL-TAL1 positive or negative T-ALL at 3 time points including: after the remission induction therapy,before delayed intensive therapy Ⅱ and before maintenance therapy. How ever,the number of cases w ith high MRD levels before consolidation therapy w ere more in SIL-TAL1 positive group than that in SIL-TAL1 negative group( P < 0. 05). The cases w ith high MRD levels before delayed intensive therapy I w as more in SIL-TAL1 negative group than that in the SIL-TAL1 positive group( P > 0. 05). Besides,there w ere no significant differences in 5-year EFS and RFS betw een the tw o groups. The risk of 22 children w ith SIL-TAL1 positive acute T-ALL w as again stratified according to the typing stemdard in CCLG-2008 protocol,as a result,the risk in BCH-2003 group( 10 cases) w as significantly higher than that in BCH-2008 group( 12 cases)( P < 0. 05),but no significant difference was found in common clinical features,early treatment response,MRD levels and treatment efficacy. Conclusions: Although WBC level w as significantly higher in SIL-TAL1 positive group than that in SIL-TAL1 negative group,the treatment efficacy in SIL-TAL1 positive group w as similar to SIL-TAL1 negative group. M eanw hile,the children w ith SIL-TAL1+T-ALL may respond poorly to early intensive therapy,the BCH-2003 protocol may be more suitable for the patients w ith this subtype of leukemia.