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应用基于实时定量 PCR 的免疫球蛋白和 T 细胞受体基因重排检测微小残留病灶在非基于微小残留病灶的 ALL IC-BFM 2002 方案中的应用:斯洛伐克的经验。

Minimal residual disease detection using real-time quantitative PCR analysis of immunoglobulin and T-cell receptor gene rearrangements in the non-MRD-based ALL IC-BFM 2002 protocol for childhood ALL: Slovak experience.

机构信息

Department of Pediatric Hematology and Oncology, Comenius University, Bratislava, Slovakia.

出版信息

Neoplasma. 2010;57(6):552-61. doi: 10.4149/neo_2010_06_552.

DOI:10.4149/neo_2010_06_552
PMID:20845994
Abstract

Acute lymphoblastic leukemia is the most common form of cancer in children. The 10-year event-free survival ranged from 77 to 85% after having achieved complete remission rates of 93% or higher. The main cause of treatment failure is relapse arising from outgrowth of residual leukemic cells that are refractory to therapy. An intense effort has been made to develop methods to determine the degree of minimal residual leukemia cells present in patients considered to be in morphological remission. Because of the strong correlation between minimal residual disease (MRD) levels and risk of relapse, monitoring of MRD provides unique information regarding treatment response. The MRD monitoring based on real-time quantitative PCR detection of patient-specific immunoglobulin and T-cell receptor (Ig/TCR) gene rearrangements is currently considered to be the most reliable tool for MRD-based diagnosis in ALL. Because the significance of MRD monitoring has been strongly supported by several studies and because it has been implemented in the latest protocols, there has been a significant effort to develop MRD monitoring in the Slovak Republic since 2005. Between October 2006 and December 2009, 50 children with ALL who were treated at three Slovak centers were included in the RQ PCR MRD pilot project. A total of 40 patients with BCP-ALL ( B cell precursor ALL) and 4 patients with T ALL were analyzed for Ig/TCR rearrangement. We identified 106 different rearrangements in the 44 ALL patients analyzed. Based on MRD stratification, we identified 26 patients who were stratified into the HRG ( high risk group) (n = 3; 11.5%), IRG ( intermediate risk group) (n = 14; 54%) and SRG ) standard risk group) (n = 9; 34.5%). Morphology-based risk stratification allows the identification of most HRG patients identified also by MRD-based stratification, but fails to discriminate the IRG assigned to therapy reduction. Patients in the SRG and the IRG could profit from MRD-based risk assignment

摘要

急性淋巴细胞白血病是儿童中最常见的癌症形式。在实现 93%或更高的完全缓解率后,10 年无事件生存率为 77%至 85%。治疗失败的主要原因是由于对治疗有抗药性的残留白血病细胞的生长而导致的复发。人们已经努力开发方法来确定被认为处于形态缓解的患者中存在的微小残留白血病细胞的程度。由于微小残留疾病 (MRD) 水平与复发风险之间存在很强的相关性,因此监测 MRD 可提供有关治疗反应的独特信息。基于实时定量 PCR 检测患者特异性免疫球蛋白和 T 细胞受体 (Ig/TCR) 基因重排的 MRD 监测目前被认为是 ALL 中基于 MRD 的诊断的最可靠工具。由于几项研究强烈支持 MRD 监测的意义,并且因为它已经在最新方案中实施,因此自 2005 年以来,斯洛伐克共和国一直在努力开展 MRD 监测。在 2006 年 10 月至 2009 年 12 月期间,在三个斯洛伐克中心接受治疗的 50 名 ALL 患儿参加了 RQ-PCR-MRD 试点项目。对 40 名 BCP-ALL(B 细胞前体 ALL)患儿和 4 名 T-ALL 患儿进行了 Ig/TCR 重排分析。在分析的 44 名 ALL 患儿中,我们确定了 106 种不同的重排。根据 MRD 分层,我们确定了 26 名患者被分为高危组(HRG)(n=3;11.5%)、中危组(IRG)(n=14;54%)和标准风险组(SRG)(n=9;34.5%)。基于形态学的风险分层可识别大多数 HRG 患者,这些患者也可通过基于 MRD 的分层来识别,但无法区分分配给减少治疗的 IRG。SRG 和 IRG 中的患者可从基于 MRD 的风险分配中获益

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