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检测非转移性神经母细胞瘤患者外周血和骨髓中的微小疾病。

Minimal disease detection in peripheral blood and bone marrow from patients with non-metastatic neuroblastoma.

机构信息

Unidad de Oncología Pediátrica, Hospital Universitario y Politécnico La Fe, Bulevar Sur S/N, 46026 Valencia, Spain.

出版信息

J Cancer Res Clin Oncol. 2011 Aug;137(8):1263-72. doi: 10.1007/s00432-011-0997-x. Epub 2011 Jun 25.

Abstract

PURPOSE

In non-metastatic neuroblastoma (NB), the identification of the cases that require more intensive treatment is still difficult. Minimal disease (MD) and minimal residual disease (MRD) detection in outcome prediction seems to be important in advanced neuroblastoma, but there are not many studies focused on patients with non-metastatic disease. The aim of this study was to determine whether the presence of MD detected at diagnosis could be associated with bad prognosis.

PROCEDURES

Quantitative reverse transcriptase-polymerase chain reaction QRT-PCR was performed on peripheral blood (PB) and bone marrow (BM) samples from patients with non-metastatic NB at diagnosis for tyrosine hydroxylase (TH) and doublecortin (DCX) mRNAs detection.

RESULTS

The frequencies of detecting MD in our series of 102 patients with non-metastatic NB were as follows: 6.2% (5/81) PB samples and 10.6% (10/94) BM samples. Overall survival was similar for patients who expressed or not the MD biomarkers at diagnosis. However, patients with MD detected in PB showed lower EFS than patients with negative PB (P = 0.038).

CONCLUSIONS

Minimal disease detection in PB seems to be useful for predicting relapse probabilities in patients with non-metastatic NB. The stages 1 and 2 patients with neuroblastoma showed high survival rates, and MD was detected in a small number of patients probably being non-contributory for predicting patient outcome. For stage 3 patients with NB, MD detection by QRT-PCR in PB at diagnosis could be useful for predicting outcome and for early and sensitive detection of relapsing disease.

摘要

目的

在非转移性神经母细胞瘤(NB)中,确定需要更强化疗的病例仍然具有挑战性。在晚期神经母细胞瘤中,微量疾病(MD)和微小残留病灶(MRD)检测在预后预测中似乎很重要,但针对非转移性疾病患者的研究并不多。本研究旨在确定在诊断时是否存在 MD 是否与不良预后相关。

方法

对 102 例非转移性 NB 患者的外周血(PB)和骨髓(BM)样本进行定量逆转录聚合酶链反应(QRT-PCR),以检测酪氨酸羟化酶(TH)和双皮质(DCX)mRNA。

结果

在我们的 81 例非转移性 NB 患者系列中,MD 的检测频率如下:PB 样本中为 6.2%(5/81),BM 样本中为 10.6%(10/94)。在诊断时表达或不表达 MD 生物标志物的患者的总体生存率相似。然而,在 PB 中检测到 MD 的患者的 EFS 低于 PB 阴性患者(P=0.038)。

结论

在 PB 中检测 MD 似乎可用于预测非转移性 NB 患者的复发概率。NB 的 1 期和 2 期患者生存率较高,少数患者检测到 MD,可能对预测患者预后无贡献。对于 NB 的 3 期患者,在诊断时通过 QRT-PCR 在 PB 中检测 MD 可能有助于预测预后,并早期、敏感地检测复发疾病。

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