Risk of Relapse of Childhood Acute Lymphoblastic Leukemia Is Predicted By Flow Cytometric Measurement of Residual Disease on Day 15 Bone Marrow
Risk of Relapse of Childhood Acute Lymphoblastic Leukemia Is Predicted By Flow Cytometric Measurement of Residual Disease on Day 15 Bone Marrow
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DOI：
10.1200/jco.2008.20.8934
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发表时间：
2009-11-01
影响因子：
45.3
通讯作者：
Gaipa, Giuseppe
中科院分区：
文献类型：
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作者：
Basso, Giuseppe;Veltroni, Marinella;Gaipa, Giuseppe
目的：细胞清除速度是儿童急性淋巴细胞白血病（ALL）预后的一个指标。在早期时间点用低成本方法测量最小残留病（MRD）的有效性具有临床意义。在2000年的AIEOP-BFM-ALL（意大利儿科肿瘤协会和柏林-法兰克福-明斯特研究组）试验中，患者在+33和+78天通过聚合酶链反应（PCR） MRD水平进行分层。AIEOP研究了诱导治疗第15天流式细胞术（FCM）测量的MRD对预后的影响。患者和方法830例意大利患者在接受类固醇治疗14天后，于第15天采集骨髓样本，同时给予甲氨蝶呤、长春新碱、柔柔比星和天冬酰胺酶一剂鞘内注射。用四色流式细胞仪检测细胞白血病相关免疫表型。结果FCM鉴定出3个患者风险组：标准组（< 0.1%，占总数的42%）、中等组（0.1 ~ < 10%，占总数的47%）和高组（0.1% ~ 10%，占总数的11%）。5年累计复发率分别为7.5% （SE, 1.5）、17.5% （SE, 2.1）、47.2% （SE, 5.9）。在多变量分析中，FCM是在第15天可用的患者中最重要的预后因素，与小于0.1%的患者相比，复发风险增加了2倍和5倍。PCR MRD加入模型后，对预后有显著影响；然而，高水平的FCM MRD保留了检测复发风险的独立能力。结论第15天骨髓FCM MRD检测是预测复发最有效的早期指标，几乎适用于所有患者；它可以补充基于PCR mrd的分层，包括较晚的时间点，从而允许额外的治疗定制。
PurposeSpeed of blast clearance is an indicator of outcome in childhood acute lymphoblastic leukemia (ALL). Availability of measurement of minimal residual disease (MRD) at an early time point with a reduced-cost method is of clinical relevance. In the AIEOP-BFM-ALL (Associazione Italiana Ematologia Oncologia Pediatrica and Berlin-Frankfurt-Munster Study Group) 2000 trial, patients were stratified by levels of polymerase chain reaction (PCR) MRD at day +33 and +78. AIEOP studied the prognostic impact of MRD measured by flow cytometry (FCM) at day 15 of induction therapy.Patients and MethodsBone marrow samples from 830 Italian patients were collected on day 15, after 14 days of steroids, and one dose of intrathecal methotrexate, vincristine, daunorubicine, and asparaginase. Cells were analyzed by four-color FCM for detection of leukemia-associated immunophenotypes.ResultsThree patient risk groups were identified by FCM: standard (< 0.1% blast cells; 42% of the total), intermediate (0.1 to < 10%; 47%), and high (> 10%; 11%). Their 5-year cumulative incidences of relapse were 7.5% (SE, 1.5), 17.5% (SE, 2.1), and 47.2% (SE, 5.9), respectively. In multivariate analysis, FCM was the most important prognostic factor among those available by day 15, with two-fold and five-fold increase in the risk of relapse compared with patients with less than 0.1%. PCR MRD, when added to the model, had significant prognostic impact; yet high levels of FCM MRD retained an independent ability to detect a significantly higher risk of relapse.ConclusionMeasurement of FCM MRD in day 15 bone marrow was the most powerful early predictor of relapse, applicable to virtually all patients; it may complement PCR MRD-based stratification including later time points, thus allowing additional treatment tailoring.