Department of Pediatrics, University of Milano-Bicocca, Ospedale S Gerardo, Monza, Italy.
Blood. 2010 Apr 22;115(16):3206-14. doi: 10.1182/blood-2009-10-248146. Epub 2010 Feb 12.
The Associazione Italiana di Ematologia Oncologia Pediatrica and the Berlin-Frankfurt-Münster 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.
意大利儿科血液学和肿瘤学会与柏林-法兰克福-明斯特急性淋巴细胞白血病（AIEOP-BFM ALL 2000）研究首次在一项大型前瞻性研究中，基于免疫球蛋白和 T 细胞受体基因重排在 2 个时间点（TP）引入标准化定量微小残留病（MRD）评估，将患者分层。前体 B（pB）ALL 患者（n=3184）如果在第 33 天（通过 2 个标志物分析，灵敏度至少为 10(-4)）已经阴性，则为 MRD 标准风险（MRD-SR）；如果在第 78 天 10(-3)或更多，则为 MRD 高风险（MRD-HR），其他为 MRD 中风险（MRD-IR）。MRD-SR 患者占 42%（1348）：5 年无事件生存率（EFS，标准误差）为 92.3%（0.9）。52%（1647）为 MRD-IR：EFS 为 77.6%（1.3）。6%的患者（189）为 MRD-HR：EFS 为 50.1%（4.1；P<0.001）。PCR-MRD 甚至在白细胞计数、年龄、早期对泼尼松的反应和基因型之上，也能区分预后。在 2 个预设 TP 通过敏感定量 PCR 检测到的 MRD 反应对儿童 pB-ALL 复发具有高度预测性。该研究在 http://clinicaltrials.gov 上登记，BFM 登记号为 NCT00430118，AIEOP 登记号为 NCT00613457。
