Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: a Children's Oncology Group study
Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: a Children's Oncology Group study
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DOI：
10.1182/blood-2008-01-132837
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发表时间：
2008-06-15
期刊：
影响因子：
20.3
通讯作者：
Camitta, Bruce M.
中科院分区：
文献类型：
--
作者：
Borowitz, Michael J.;Devidas, Meenakshi;Camitta, Bruce M.
微小残留病（MRD）是急性淋巴细胞白血病（ALL）复发的重要预测因子，但其与其他预后变量的关系尚未得到充分评估。儿童肿瘤学小组研究了2143例前体B细胞ALL（B-ALL）儿童在第8天外周血、诱导终末（第29天）和实变终末骨髓中通过流式细胞术测量MRD的预后影响。在所有风险组中，第8天血液和第29天骨髓MRD中存在MRD与较短的无事件生存期（EFS）相关;即使第29天MRD为0.01%至0.1%的患者与MRD阴性患者相比，结局也较差（59% +/- 5% vs 88% +/- 1% 5年EFS）。良好预后标志物TEL-AML 1或4号和10号染色体三体的存在仍然提供了额外的预后信息，但在MRD+的国家癌症研究所高危（NCI HR）患者中则不然。少数在巩固治疗结束时可检测到MRD的患者表现尤其差，5年EFS仅为43% ± 7%。在多变量分析中，第29天骨髓MRD是最重要的预后变量。12%的患者具有所有有利的风险因素，包括NCI风险组、遗传学和没有第8天和第29天的MRD，非强化治疗的5年EFS为97% ± 1%。这些研究在www.clinicaltrials.gov上注册为NCT 00005585、NCT 00005596和NCT 00005603。
Minimal residual disease (MRD) is an important predictor of relapse in acute lymphoblastic leukemia (ALL), but its relationship to other prognostic variables has not been fully assessed. The Children's Oncology Group studied the prognostic impact of MRD measured by flow cytometry in the peripheral blood at day 8, and in end-induction (day 29) and end-consolidation marrows in 2143 children with precursor B-cell ALL (B-ALL). The presence of MRD in day-8 blood and day-29 marrow MRD was associated with shorter event-free survival (EFS) in all risk groups; even patients with 0.01% to 0.1% day-29 MRD had poor outcome compared with patients negative for MRD patients (59% +/- 5% vs 88% +/- 1% 5-year EFS). Presence of good prognostic markers TEL-AML1 or trisomies of chromosomes 4 and 10 still provided additional prognostic information, but not in National Cancer Insitute high-risk (NCI HR) patients who were MRD+. The few patients with detectable MRD at end of consolidation fared especially poorly, with only a 43% plus or minus 7% 5-year EFS. Day-29 marrow MRD was the most important prognostic variable in multi-variate analysis. The 12% of patients with all favorable risk factors, including NCI risk group, genetics, and absence of days 8 and 29 MRD, had a 97% plus or minus 1% 5-year EFS with nonintensive therapy. These studies are registered at www.clinicaltrials.gov as NCT00005585, NCT00005596, and NCT00005603.