Clinical importance of minimal residual disease in childhood acute lymphoblastic leukemia
Clinical importance of minimal residual disease in childhood acute lymphoblastic leukemia
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DOI：
10.1182/blood.v96.8.2691
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发表时间：
2000-10-15
期刊：
影响因子：
20.3
通讯作者：
Campana, D
中科院分区：
文献类型：
--
作者：
Coustan-Smith, E;Sancho, J;Campana, D
通过使用能够在10(4)个正常细胞中检测一个白血病细胞的快速流式细胞术技术，我们前瞻性地研究了195例临床缓解的新诊断急性淋巴细胞白血病（ALL）儿童的微小残留病（MRD）。在缓解诱导治疗结束时和之后每隔3次收集骨髓抽吸物（n = 629）。可检测的磁共振成像（MRD）。大于或等于0.01%白血病单核细胞)的患者复发率较高（P < 0.001）；在诱导期结束时（1%）或在继续治疗第14周时（大于或等于0.1%）MRD水平高的患者预后特别差。即使在调整了不良表现特征后，排除了复发风险极高或极低的患者，并考虑了诱导治疗第7天和第10天的外周血淋巴细胞水平，MRD的预测强度仍然显著。在诱导期结束时，MRD患者的复发率为68% +/- 16% (SE)，如果他们在持续治疗的第14周保持MRD，与7% +/- 7%的MRD无法检测（P = 0.035）相比，MRD持续到第32周是复发的高度预测(所有4名MRD+患者复发，而8名转化为无法检测的MRD状态的患者中有2名复发；P = 0.021)，通过本文描述的方法对MRD进行序贯监测，为ALL患儿提供了非常重要的独立预后信息。最近流式细胞测定的改进使其适用于90%以上的新患者。(C) 2000年由美国血液学会出版。
By using rapid flow cytometric techniques capable of detecting one leukemic cell in 10(4) normal cells, we prospectively studied minimal residual disease (MRD) in 195 children with newly diagnosed acute lymphoblastic leukemia (ALL) in clinical remission. Bone marrow aspirates (n = 629) were collected at the end of remission induction therapy and at 3 intervals thereafter. Detectable MRD (ie. greater than or equal to 0.01% leukemic mononuclear cells) at each time point was associated with a higher relapse rate (P < .001); patients with high levels of MRD at the end of the induction phase ( 1%) or at week 14 of continuation therapy (greater than or equal to 0.1 %) had a particularly poor outcome. The predictive strength of MRD remained significant even after adjusting for adverse presenting features, excluding patients at very high or very low risk of relapse from the analysis, and considering levels of peripheral blood lymphoblasts at day 7 and day 10 of induction therapy. The incidence of relapse among patients with MRD at the end of the induction phase was 68% +/- 16% (SE) ii they remained with MRD through week 14 of continuation therapy, compared with 7% +/- 7% ii MRD became undetectable (P = .035), The persistence of MRD until week 32 was highly predictive of relapse (all 4 MRD+ patients relapsed vs 2 of the 8 who converted to undetectable MRD status; P = .021), Sequential monitoring of MRD by the method described here provides highly significant, independent prognostic information in children with ALL. Recent improvements in this flow cytometric assay have made it applicable to more than 90% of all new patients. (C) 2000 by The American Society of Hematology.