University of Ulm, Children's Hospital, Ulm, Germany.
University of Frankfurt, Children's Hospital, Frankfurt, Germany.
Clin Cancer Res. 2015 Mar 15;21(6):1353-9. doi: 10.1158/1078-0432.CCR-14-1999. Epub 2014 Dec 11.
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).
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.
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.
This novel method of monitoring MRD has a strong prognostic impact that is independent from established risk factors in childhood AML.
本研究评估了一种新型、简单且标准化的检测方法，用于监测儿科急性髓系白血病（AML）的微小残留病（MRD）。
通过 TaqMan 低密度阵列在 112 名患者和 52 名健康对照中检测七种白血病相关基因（WT1、PRAME、CCL23、GAGED2、MSLN、SPAG6 和 ST18）的表达。患者根据多中心研究 AML-BFM 2004 进行治疗。在标准时间点前瞻性采集样本。测量 MRD 的实验室对患者的结果不知情。
如果所有基因在第 15 天表达降至正常，无复发生存率（RFS）为 95%（N = 19；SE = 5%）；如果在第 28 天表达正常化，RFS 为 63%（N = 41；SE = 8%）；如果在第 28 天仍显示升高的表达，RFS 为 38%（N = 21；SE = 11%）。当根据 AML-BFM 2004 风险组对患者进行分层时，MRD 的预后影响仍然显著（P = 0.002）。多变量分析确定了 MRD 风险组和第 28 天细胞形态学是唯一的独立预后因素。第 28 天细胞形态学未缓解的患者（通过 MRD 确认）预后不佳。8 名患者中只有 1 名未复发而存活。
这种监测 MRD 的新方法具有强烈的预后影响，独立于儿童 AML 中的既定危险因素。
