The prognostic value of fast molecular response of marrow disease in patients aged over 1 year with stage 4 neuroblastoma
The prognostic value of fast molecular response of marrow disease in patients aged over 1 year with stage 4 neuroblastoma
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DOI：
10.1016/j.ejca.2011.02.003
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发表时间：
2011-05-01
影响因子：
8.4
通讯作者：
Tytgat, G. A. M.
中科院分区：
文献类型：
--
作者：
Stutterheim, J.;Zappeij-Kannegieter, L.;Tytgat, G. A. M.
背景：用于检测神经母细胞瘤（NB）儿童微小残留病（MRD）的定量实时（q）PCR可以评估分子骨髓（BM）对治疗的反应，但诱导治疗期间BM中肿瘤动力学的预后价值仍有待确定。本研究的目的是分析在哪些时间点通过 BM 序贯分子评估进行 MRD 检测可预测总生存期 (OS)。 方法：在这项单中心研究中，使用 5 种 NB 特异性标记物：PHOX2B、TH、DDC、GAP43 和 CHRNA3，对 53 名 1 年以上 4 期神经母细胞瘤患者的 106 份 BM 样本进行了回顾性分析，进行了 qPCR。使用单变量和双变量 Cox 回归分析评估诊断时 (n = 39)、诊断后 3 个月 (n = 38) 和完成诱导化疗 (n = 29) 时 MRD 的预后影响。结果：诊断时肿瘤负荷与结果之间不存在相关性 (p = 0.93)。诊断后 3 个月时，11/38 (29%) 的患者观察到分子 BM 缓解，并且与良好的结局相关（5-y-OS 62 +/- 15.0% 对比 19 8%；p = 0.009）。诱导化疗完成后，41% (12/29) 的患者 BM 仍为 MRD 阳性，这与不良预后相关（5-y-OS 0% 对比 52 +/- 12%；p < 0.001）。对于这两个时间点，分子反应的预后价值在双变量分析中仍然显着。结论：通过一组 NB 特异性 PCR 靶标测量的 MRD 检测可以识别快速反应者，他们在治疗期间早期清除了 BM。快速的分子反应是一个预后因素，与更好的结果相关。我们的数据表明，诱导治疗期间的 MRD 分析应纳入前瞻性 MRD 研究。 (C) 2011 Elsevier Ltd. 保留所有权利。
Background: Quantitative real-time (q)PCR for detection of minimal residual disease (MRD) in children with neuroblastoma (NB) can evaluate molecular bone marrow (BM) response to therapy, but the prognostic value of tumour kinetics in the BM during induction treatment remains to be established. The purpose of this study was to analyse at which time points MRD detection by sequential molecular assessment of BM was prognostic for overall survival (OS).Methods: In this single centre study, qPCR was performed with five NB-specific markers: PHOX2B, TH, DDC, GAP43 and CHRNA3, on 106 retrospectively analysed BM samples of 53 patients >1 year with stage 4 neuroblastoma. The prognostic impact of MRD at diagnosis (n = 39), at 3 months after diagnosis (n = 38) and after completing induction chemotherapy (n = 29) was assessed using univariate and bivariate Cox regression analyses.Results: There was no correlation between tumour load at diagnosis and outcome (p = 0.93). Molecular BM remission was observed in 11/38 (29%) of patients at 3 months after diagnosis and associated with favourable outcome (5-y-OS 62 +/- 15.0% versus 19 8%; p = 0.009). After completion of induction chemotherapy, BM of 41% (12/29) of the patients was still MRD positive, which was associated with poor outcome (5-y-OS 0% versus 52 +/- 12%; p < 0.001). For both time points, the prognostic value of molecular response remained significant in bivariate analysis.Conclusions: MRD detection measured by a panel of NB specific-PCR targets could identify fast responders, who clear their BM early during treatment. Fast molecular response was a prognostic factor, associated with better outcome. Our data indicate that MRD analysis during induction therapy should be included in prospective MRD studies. (C) 2011 Elsevier Ltd. All rights reserved.