Prospective Validation of a New Method of Monitoring Minimal Residual Disease in Childhood Acute Myelogenous Leukemia
Prospective Validation of a New Method of Monitoring Minimal Residual Disease in Childhood Acute Myelogenous Leukemia
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DOI：
10.1158/1078-0432.ccr-14-1999
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发表时间：
2015-03-15
影响因子：
11.5
通讯作者：
Gruhn, Bernd
中科院分区：
文献类型：
--
作者：
Steinbach, Daniel;Bader, Peter;Gruhn, Bernd
目的：本研究评价了一种新的、简单的、标准化的检测方法对儿童急性髓细胞性白血病（AML）微小残留病（MRD）的预后影响。实验设计：采用TaqMan低密度芯片检测了112例患者和52例健康对照中7个白血病相关基因（WT 1、PRAME、CCL 23、GAGED 2、MSLN、SPAG 6和ST 18）的表达。根据多中心研究AML-BFM 2004对患者进行治疗。在标准时间点前瞻性采集样本。测量MRD的实验室对患者结果不知情。结果：无复发生存率（RFS）为95%（N = 19; SE = 5%）如果所有基因的表达在第15天降至正常，则63%（N = 41; SE = 8%），在第28天表达正常化的患者中为38%（N = 21; SE = 11%）。当患者按照AML-BFM 2004风险组分层时，MRD的预后影响仍然显著（P = 0.002）。多变量分析确定MRD风险组和第28天细胞学检查为唯一的独立预后因素。第28天细胞学未缓解的患者，经MRD证实，预后不良。8例患者中只有1例存活而无复发。结论：这种监测MRD的新方法具有很强的预后影响，独立于儿童AML的既定危险因素。(C)2014年AACR。
Purpose: This study evaluated the prognostic impact of a novel, simple, and standardized assay for monitoring minimal residual disease (MRD) in pediatric acute myelogenous leukemia (AML).Experimental Design: The expression of seven leukemia-associated genes (WT1, PRAME, CCL23, GAGED2, MSLN, SPAG6, and ST18) was measured by TaqMan Low Density Arrays in 112 patients and 52 healthy controls. Patients were treated according to the multicenter study AML-BFM 2004. Samples were collected prospectively at standard time points. The laboratory that measured MRD was blinded to patient outcome.Results: Relapse-free survival (RFS) was 95% (N = 19; SE = 5%) if expression of all genes was down to normal on day 15,63% (N = 41; SE = 8%) if expression was normalized on day 28, and 38% (N = 21; SE = 11%) in patients who still showed elevated expression on day 28. The prognostic impact of MRD remained significant (P = 0.002) when patients were stratified for the AML-BFM 2004 risk group. Multivariate analysis identified the MRD risk group and day 28 cytology as the only independent prognostic factors. Patients with a cytologic nonremission on day 28, which was confirmed by MRD, had a dismal prognosis. Only 1 out of 8 patients survived without relapse.Conclusions: This novel method of monitoring MRD has a strong prognostic impact that is independent from established risk factors in childhood AML. (C) 2014 AACR.