Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia. European Organization for Research and Treatment of Cancer--Childhood Leukemia Cooperative Group.
Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia. European Organization for Research and Treatment of Cancer--Childhood Leukemia Cooperative Group.
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发表时间：
1998
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通讯作者：
H. Cavé;J. van der Werff Ten Bosch;S. Suciu;C. Guidal;C. Waterkeyn;J. Otten;M. Bakkus;K. Thielemans;B. Grandchamp;E. Vilmer
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作者：
H. Cavé;J. van der Werff Ten Bosch;S. Suciu;C. Guidal;C. Waterkeyn;J. Otten;M. Bakkus;K. Thielemans;B. Grandchamp;E. Vilmer
背景与方法急性淋巴细胞白血病（ALL）治疗后残留病变检测的意义尚不清楚。我们在11个中心进行了一项前瞻性研究，以确定在诱导儿童ALL完全缓解后的前6个月的几个时间点是否存在可检测残留疾病的预测价值。使用t细胞受体或免疫球蛋白基因重排的连接序列作为白血病细胞的克隆标记。残留病用竞争性聚合酶链反应（PCR）测定。在诊断和统一化疗方案治疗的246名患者中，178名患者使用一个克隆特异性探针（74%）或多个探针（26%）监测残留疾病。中位随访期为38个月。结果在每个研究时间点（P或=10（-2）残留细胞）或较晚时间点（>或=10（-3）残留细胞），残留白血病的存在或不存在及水平与早期复发的风险显著相关。多因素分析显示，与免疫表型、年龄、危险组（标准或高危）、诊断时白细胞计数相比，是否存在和残留疾病水平是最重要的独立预后因素。结论：诱导缓解后的残留白血病是儿童ALL的一个重要预后因素。通过聚合酶链反应检测残留疾病应用于识别有复发风险的患者，并应在考虑替代治疗时予以考虑。
BACKGROUND AND METHODS The implications of the detection of residual disease after treatment of acute lymphoblastic leukemia (ALL) are unclear. We conducted a prospective study at 11 centers to determine the predictive value of the presence or absence of detectable residual disease at several points in time during the first six months after complete remission of childhood ALL had been induced. Junctional sequences of T-cell-receptor or immunoglobulin gene rearrangements were used as clonal markers of leukemic cells. Residual disease was quantitated with a competitive polymerase-chain-reaction (PCR) assay. Of 246 patients enrolled at diagnosis and treated with a uniform chemotherapy protocol, 178 were monitored for residual disease with one clone-specific probe (in 74 percent) or more than one probe (in 26 percent). The median follow-up period was 38 months. RESULTS The presence or absence and level of residual leukemia were significantly correlated with the risk of early relapse at each of the times studied (P or =10(-2) residual blasts) or at later time points (those with > or =10(-3) residual blasts). Multivariate analysis showed that as compared with immunophenotype, age, risk group (standard or very high risk), and white-cell count at diagnosis, the presence or absence and level of residual disease were the most powerful independent prognostic factors. CONCLUSIONS Residual leukemia after induction of a remission is a powerful prognostic factor in childhood ALL. Detection of residual disease by PCR should be used to identify patients at risk for relapse and should be taken into account in considering alternative treatment.