Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP-BFM ALL 2000 study
Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP-BFM ALL 2000 study
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DOI：
10.1182/blood-2009-10-248146
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发表时间：
2010-04-22
期刊：
影响因子：
20.3
通讯作者：
Schrappe, Martin
中科院分区：
文献类型：
--
作者：
Conter, Valentino;Bartram, Claus R.;Schrappe, Martin
在一项大型前瞻性研究中，意大利儿科肿瘤协会和柏林-法兰克福-明斯特急性淋巴母细胞白血病（AIEOP-BFM ALL 2000）研究首次引入了基于免疫球蛋白和t细胞受体基因重排作为聚合酶链反应靶点（PCR-MRD）的最小残留病（MRD）的标准化定量评估，在2个时间点（tp）对患者进行分层。前体B (pB) ALL患者（n = 3184）如果在第33天MRD已经为阴性，则认为MRD标准风险（MRD- sr）（通过2种标志物分析，敏感性至少为10(-4)）；MRD高风险（MRD- hr）如果在第78天10（-3）或更多，MRD中度风险（MRD- ir）：其他。MRD-SR患者为42%(1348):5年无事件生存率（EFS，标准误差）为92.3%（0.9）。52%（1647例）为MRD-IR， 77.6%（1.3例）为EFS。6%的患者（189例）为MRD-HR: EFS为50.1% （4.1;P < 0.001）。PCR-MRD甚至在白细胞计数、年龄、对强的松的早期反应和基因型的基础上区分预后。在2个预先定义的TPs处，通过敏感的定量PCR检测MRD反应，可以高度预测儿童pB-ALL的复发。该研究注册于http://clinicaltrials.gov: BFM为NCT00430118， AIEOP为NCT00613457。[血液。2010;115(16):3206-3214]
The Associazione Italiana di Ematologia Oncologia Pediatrica and the Berlin-Frankfurt-Munster Acute Lymphoblastic Leukemia (AIEOP-BFM ALL 2000) study has for the first time introduced standardized quantitative assessment of minimal residual disease (MRD) based on immunoglobulin and T-cell receptor gene rearrangements as polymerase chain reaction targets (PCR-MRD), at 2 time points (TPs), to stratify patients in a large prospective study. Patients with precursor B (pB) ALL (n = 3184) were considered MRD standard risk (MRD-SR) if MRD was already negative at day 33 (analyzed by 2 markers, with a sensitivity of at least 10(-4)); MRD high risk (MRD-HR) if 10(-3) or more at day 78 and MRD intermediate risk (MRD-IR): others. MRD-SR patients were 42% (1348): 5-year event-free survival (EFS, standard error) is 92.3% (0.9). Fifty-two percent (1647) were MRD-IR: EFS 77.6% (1.3). Six percent of patients (189) were MRD-HR: EFS 50.1% (4.1; P < .001). PCR-MRD discriminated prognosis even on top of white blood cell count, age, early response to prednisone, and genotype. MRD response detected by sensitive quantitative PCR at 2 predefined TPs is highly predictive for relapse in childhood pB-ALL. The study is registered at http://clinicaltrials.gov: NCT00430118 for BFM and NCT00613457 for AIEOP. (Blood. 2010; 115(16): 3206-3214)