Late MRD response determines relapse risk overall and in subsets of childhood T-cell ALL: results of the AIEOP-BFM-ALL 2000 study
Late MRD response determines relapse risk overall and in subsets of childhood T-cell ALL: results of the AIEOP-BFM-ALL 2000 study
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DOI：
10.1182/blood-2011-03-338707
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发表时间：
2011-08-25
期刊：
影响因子：
20.3
通讯作者：
Conter, Valentino
中科院分区：
文献类型：
--
作者：
Schrappe, Martin;Valsecchi, Maria Grazia;Conter, Valentino
MRD在大系列儿童T-ALL中的预后价值尚未确定。试验AIEOP-BFM-ALL 2000基于免疫球蛋白和TCR基因重排作为聚合酶链反应靶点，引入了MRD分层的标准化定量评估：如果第33天MRD为阴性，则认为患者存在MRD标准风险（MRD-SR（时间点1 [TP 1]）和第78天（TP 2），通过至少2种敏感标志物进行分析;如果在第33天或第78天呈阳性且第78天< 10（-3），则为MRD中等风险（MRD-IR）;如果在第78天>= 10（-3），则为MRD高风险（MRD-HR）。根据MRD对464例T-ALL患者进行分层，其中16%为MRD-SR，63%为MRD-IR，21%为MRD-HR，其7年无事件生存率（SE）分别为91.1%（3.5%）、80.6%（2.3%）和49.8%（5.1%）（P <0.001）。TP 1时MRD阴性是最有利的预后因素。仅在TP 2时MRD转为阴性的32%患者也获得了极好的结局，表明如果TP 2时MRD为阴性，则早期（TP 1）MRD水平无关紧要（所有患者的48%）。TP 2时MRD >= 10（-3）是儿童T-ALL复发的最重要预测因素。该研究在http://www.clinicaltrials.gov注册;“基于复发风险的联合化疗治疗急性淋巴细胞白血病年轻患者”，BFM的方案识别号为NCT 00430118，AIEOP的方案识别号为NCT 00613457。（血。2011;118（8）：2077-2084）
The prognostic value of MRD in large series of childhood T-ALL has not yet been established. Trial AIEOP-BFM-ALL 2000 introduced standardized quantitative assessment of MRD for stratification, based on immunoglobulin and TCR gene rearrangements as polymerase chain reaction targets: Patients were considered MRD standard risk (MRD-SR) if MRD was negative at day 33 (time point 1 [TP1]) and day 78 (TP2), analyzed by at least 2 sensitive markers; MRD intermediate risk (MRD-IR) if positive either at day 33 or 78 and < 10(-3) at day 78; and MRD high risk (MRD-HR) if >= 10(-3) at day 78. A total of 464 patients with T-ALL were stratified by MRD: 16% of them were MRD-SR, 63% MRD-IR, and 21% MRD-HR. Their 7-year event-free-survival (SE) was 91.1% (3.5%), 80.6% (2.3%), and 49.8% (5.1%) (P < .001), respectively. Negativity of MRD at TP1 was the most favorable prognostic factor. An excellent outcome was also obtained in 32% of patients turning MRD negative only at TP2, indicating that early (TP1) MRD levels were irrelevant if MRD at TP2 was negative (48% of all patients). MRD >= 10(-3) at TP2 constitutes the most important predictive factor for relapse in childhood T-ALL. The study is registered at http://www.clinicaltrials.gov; "Combination Chemotherapy Based on Risk of Relapse in Treating Young Patients With Acute Lymphoblastic Leukemia," protocol identification #NCT00430118 for BFM and #NCT00613457 for AIEOP. (Blood. 2011;118(8):2077-2084)