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Integrated Risk Stratification Using Minimal Residual Disease and Sentinel Genetic Alterations in Pediatric Acute Lymphoblastic Leukemia
Journal of Clinical Oncology ( IF 42.1 ) Pub Date : 2018-01-01 , DOI: 10.1200/jco.2017.76.0504
Stephen P. Hunger 1
Affiliation  

Treatment of pediatric acute lymphoblastic leukemia (ALL) has provided a paradigm for cancer therapy since 1948, when Farber and Diamond1 first demonstrated that chemotherapy could induce remission in human cancer. Once curative therapies for ALL were developed, age and WBC count at diagnosis were identified as important prognostic factors that were predictive of response and outcome.2 It was later found that early response to therapy—as measured by morphologic clearance of blasts from the blood or marrow during induction therapy—was a strong predictor of outcome.3,4 It is now recognized that detection of minimal residual disease (MRD) by either PCR amplification of clonotypic IG/TCR gene rearrangements or flow cytometric detection of leukemia-associated phenotypes is perhaps the strongest predictor of event-free survival (EFS) and overall survival (OS).5-7 The presence of specific recurrent sentinel genetic lesions in leukemia cells is also a powerful prognostic factor.8 There is general agreement, not universal, that good risk factors include ETV6-RUNX1 fusion and high hyperdiploidy and/or favorable chromosome trisomies, whereas poor risk factors include BCR-ABL1 fusion, KMT2A (MLL) gene fusions, intrachromosomal amplification of chromosome 21 (iAMP21), and hypodiploidy.

中文翻译:

小儿急性淋巴细胞白血病中使用最小残留疾病和前哨遗传改变的综合风险分层

自1948年以来,小儿急性淋巴细胞白血病(ALL)的治疗为癌症治疗提供了范例,当时Farber和Diamond 1首次证明化学疗法可以诱导人类癌症的缓解。一旦制定了ALL的根治性疗法,就将诊断时的年龄和WBC计数确定为可预测疗效和预后的重要预后因素。2后来发现,对治疗的早期反应(通过诱导治疗期间血液或骨髓中胚泡的形态清除率来衡量)可以作为预后的有力预测指标。3,4现在公认,通过克隆型IG / TCR的任一PCR扩增检测最小残留疾病(MRD)白血病相关表型的基因重排或流式细胞术检测可能是无事件生存期(EFS)和总体生存期(OS)的最强预测指标。5-7白血病细胞中特定的复发性前哨遗传病灶的存在也是一个强大的预后因素。8普遍同意,并非普遍,好的风险因素包括ETV6 - RUNX1融合和高二倍体和/或有利的染色体三体性,而差的风险因素包括BCR - ABL1融合,KMT2AMLL)基因融合,21号染色体的染色体内扩增(iAMP21)和二倍体。
更新日期:2017-12-31
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