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[儿童急性髓系白血病的遗传预后因素]

[Genetic prognostic factors in childhood acute myeloid leukemia].

作者信息

Reinhardt D, Von Neuhoff C, Sander A, Creutzig U

机构信息

Pädiatrische Onkologie und Hämatologie, Medizinische Hochschule Hannover.

出版信息

Klin Padiatr. 2012 Oct;224(6):372-6. doi: 10.1055/s-0032-1312611. Epub 2012 Jul 20.

Abstract

The survival rate of children and adolescents suffering acute myeloid leukemia (AML) has been significantly improved within the last decades. This has been achieved by a continuously intensified therapy and progress in supportive care to prevent and treat complications. In Germany, the AML-BFM trials 98 (n=413) and 2004 (n=499) enrolled 912 children and adolescents as protocol patients (1998-2010). The 5-year-overall survival was 71±2%. In the previous studies prognosis and subsequent treatment stratification based on morphology, cytochemistry and white blood cell count. Today, the identification of new genetic aberrations in AML enables a genetically determined estimation of prognosis, although treatment response must be considered for treatment stratification. The group with a favorable prognosis summarized AML with t(8;21), inv(16), t(15;17), t(1;11), and AML with normal karyotype and NPM1-mutation (n=253; EFS 74±3%, OS 88±2%). A poor prognosis (HR-group) must be expected in AML with t(4;11), t(5;11), t(6;11), t(6;9), t(7;12), t(9;22), Monosomy 7, combined FLT3/WT1-mutation, and AML with der(12p)-aberration (n=101; EFS 30±5%; OS 56±5%). The intermediate group summarizes all other subgroups especially AML with normal karyotyp, AML with FLT3-ITD or t(9;11) (n=558; EFS 43±2%; OS 64±2%). The validation of the internationally identified, genetically determined prognostic factors within the AML-BFM (Germany) study population will support treatment recommendations.

摘要

在过去几十年中,患有急性髓系白血病(AML)的儿童和青少年的生存率有了显著提高。这是通过持续强化治疗以及在预防和治疗并发症的支持性护理方面取得的进展实现的。在德国,AML-BFM试验98(n = 413)和2004(n = 499)将912名儿童和青少年纳入方案患者(1998 - 2010年)。5年总生存率为71±2%。在先前的研究中,预后和后续治疗分层基于形态学、细胞化学和白细胞计数。如今,AML中新遗传异常的鉴定使得能够基于基因确定预后评估,不过在进行治疗分层时必须考虑治疗反应。预后良好的组包括伴有t(8;21)、inv(16)、t(15;17)、t(1;11)的AML,以及核型正常且NPM1突变的AML(n = 253;无事件生存率74±3%,总生存率88±2%)。伴有t(4;11)、t(5;11)、t(6;11)、t(6;9)、t(7;12)、t(9;22)、7号染色体单体、FLT3/WT1联合突变以及伴有der(12p)异常的AML预计预后较差(高危组)(n = 101;无事件生存率30±5%;总生存率56±5%)。中间组包括所有其他亚组,尤其是核型正常的AML、伴有FLT3-ITD或t(9;11)的AML(n = 558;无事件生存率43±2%;总生存率64±2%)。在AML-BFM(德国)研究人群中对国际上确定的、基于基因的预后因素进行验证将有助于支持治疗建议。

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