[微小残留病检测在儿童B细胞急性淋巴细胞白血病治疗中的临床重要性]

[Clinical importance of minimal residual disease testing in the therapy of childhood B-cell acute lymphoblastic leukemia].

作者信息

Ye Qi-Dong, Gu Long-Jun, Tang Jing-Yan, Xue Hui-Liang, Chen Jing, Pan Ci, Chen Jing, Dong Lu, Zhou Min, Jiang Li-Min

机构信息

Department of Hematology/Oncology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.

出版信息

Zhongguo Dang Dai Er Ke Za Zhi. 2008 Jun;10(3):333-6.

PMID:18554462

Abstract

OBJECTIVE

To study the role of minimal residual disease (MRD) in the evaluation of therapeutic effectiveness of childhood B-cell acute lymphoblastic leukemia (ALL).

METHODS

MRD testing was performed in 124 children with B-cell ALL, who were newly diagnosed and enrolled in the ALL-XH-99 treatment protocol from September 2001 to April 2005MRD was determined by 4-color flow cytometry in the different time points during the treatment period.

RESULTS

After induction therapy, 103, 13 and 8 patients showed MRD <0.01%, 0.01%-0.1% and >0.1%, respectively. The 5-year relapse-free survival (RFS) in the patients with MRD <0.01%, 0.01%-0.1% and >0.1% was 88.9+/-3.9%, 70.0+/-14.5% and 0%, respectively and the 5-year event-free survival (EFS) was 82.4+/-4.4%, 21.2+/-18.0% and 0%, respectively. There were significant differences in the RFS and EFS among the patients with different MRD levels (P<0.01). Within half a year after induction remission, the 5-year RFS in patients with MRD negative (<0.01%) and positive was 87.7+/-4.1% and 58.3+/-14.2%, respectively (P<0.01) and the 5-year RFS was 80.7+/-4.6% and 25.6+/-13.8%, respectively (P<0.01). After half a year with induction remission, the patients with MRD negative and positive also showed statistical differences in the 5-year RFS (92.0+/-3.6% vs 48.5+/-15.5%; P<0.01) and EFS (85.6+/-4.5% vs 21.4+/-11.0%; P<0.01). Multivariate analysis confirmed that the MRD level after induction chemotherapy together with the reaction to prednisone, the bone marrow features on the 19th day of induction, and the fusion gene with BCR-ABL or MLL-AF4 had prognostic significance in childhood B-cell ALL.

CONCLUSIONS

The MRD level in the whole course of therapy is an important outcome indicator in childhood B cell ALL.

摘要

目的

研究微小残留病（MRD）在儿童B细胞急性淋巴细胞白血病（ALL）治疗效果评估中的作用。

方法

对124例新诊断的B细胞ALL患儿进行MRD检测，这些患儿于2001年9月至2005年4月纳入ALL-XH-99治疗方案。在治疗期间的不同时间点通过四色流式细胞术测定MRD。

结果

诱导治疗后，103例、13例和8例患者的MRD分别<0.01%、0.01%-0.1%和>0.1%。MRD<0.01%、0.01%-0.1%和>0.1%的患者5年无复发生存率（RFS）分别为88.9±3.9%、70.0±14.5%和0%，5年无事件生存率（EFS）分别为82.4±4.4%、21.2±18.0%和0%。不同MRD水平的患者在RFS和EFS方面存在显著差异（P<0.01）。诱导缓解后半年内，MRD阴性（<0.01%）和阳性患者的5年RFS分别为87.7±4.1%和58.3±14.2%（P<0.01），5年RFS分别为80.7±4.6%和25.6±13.8%（P<0.01）。诱导缓解半年后，MRD阴性和阳性患者在5年RFS（92.0±3.6%对48.5±15.5%；P<0.01）和EFS（85.6±4.5%对21.4±11.0%；P<0.01）方面也存在统计学差异。多因素分析证实，诱导化疗后的MRD水平连同对泼尼松的反应、诱导第19天的骨髓特征以及与BCR-ABL或MLL-AF4的融合基因在儿童B细胞ALL中具有预后意义。