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Abstract：
BACKGROUND: Quantitative measurement of minimal residual disease (MRD) is the \"gold standard\" for estimating the response to therapy in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Nevertheless, the speed of the MRD response differs for different cytogenetic subgroups. Here we present results of MRD measurement in children with BCP-ALL, in terms of genetic subgroups with relation to clinically defined risk groups.
METHODS: A total of 485 children with non-high-risk BCP-ALL with available cytogenetic data and MRD studied at the end-of-induction (EOI) by multicolor flow cytometry (MFC) were included. All patients were treated with standard-risk (SR) of intermediate-risk (ImR) regimens of \"ALL-MB 2008\" reduced-intensity protocol.
CONCLUSIONS: Among all study group patients, 203 were found to have low-risk cytogenetics (ETV6::RUNX1 or high hyperdiploidy), while remaining 282 children were classified in intermediate cytogenetic risk group. For the patients with favorable and intermediate risk cytogenetics, the most significant thresholds for MFC-MRD values were different: 0.03% and 0.04% respectively. Nevertheless, the most meaningful thresholds were different for clinically defined SR and ImR groups. For the SR group, irrespective to presence/absence of favorable genetic lesions, MFC-MRD threshold of 0.1% was the most clinically valuable, although for ImR group the most informative thresholds were different in patients from low-(0.03%) and intermediate (0.01%) cytogenetic risk groups.
CONCLUSIONS: Our data show that combining clinical risk factors with MFC-MRD measurement is the most useful tool for risk group stratification of children with BCP-ALL in the reduced-intensity protocols. However, this algorithm can be supplemented with cytogenetic data for part of the ImR group.
METHODS: A total of 485 children with non-high-risk BCP-ALL with available cytogenetic data and MRD studied at the end-of-induction (EOI) by multicolor flow cytometry (MFC) were included. All patients were treated with standard-risk (SR) of intermediate-risk (ImR) regimens of \"ALL-MB 2008\" reduced-intensity protocol.
CONCLUSIONS: Among all study group patients, 203 were found to have low-risk cytogenetics (ETV6::RUNX1 or high hyperdiploidy), while remaining 282 children were classified in intermediate cytogenetic risk group. For the patients with favorable and intermediate risk cytogenetics, the most significant thresholds for MFC-MRD values were different: 0.03% and 0.04% respectively. Nevertheless, the most meaningful thresholds were different for clinically defined SR and ImR groups. For the SR group, irrespective to presence/absence of favorable genetic lesions, MFC-MRD threshold of 0.1% was the most clinically valuable, although for ImR group the most informative thresholds were different in patients from low-(0.03%) and intermediate (0.01%) cytogenetic risk groups.
CONCLUSIONS: Our data show that combining clinical risk factors with MFC-MRD measurement is the most useful tool for risk group stratification of children with BCP-ALL in the reduced-intensity protocols. However, this algorithm can be supplemented with cytogenetic data for part of the ImR group.
摘要：
背景：微小残留病（MRD）的定量测量是评估儿童B细胞前体急性淋巴细胞白血病（BCP-ALL）治疗反应的“金标准”。然而，不同细胞遗传学亚群的MRD反应速度不同.在这里，我们介绍了BCP-ALL儿童的MRD测量结果，就与临床定义的风险组相关的遗传亚组而言。
方法：纳入了485名非高危BCP-ALL患儿，这些患儿具有可用的细胞遗传学数据，并通过多色流式细胞术（MFC）在诱导末期（EOI）进行了MRD研究。所有患者均接受“ALL-MB2008”降低强度方案的标准风险（SR）中危（ImR）方案治疗。
结论：在所有研究组患者中，发现203具有低风险的细胞遗传学（ETV6::RUNX1或高超二倍体），而其余282名儿童被归类为中等细胞遗传学风险组。对于具有有利和中等风险细胞遗传学的患者，MFC-MRD值的最显著阈值不同:分别为0.03%和0.04%.然而，临床定义的SR和ImR组的最有意义的阈值不同.对于SR组，无论是否存在/不存在有利的遗传病变，MFC-MRD阈值为0.1%是最具临床价值的，尽管ImR组的信息最丰富的阈值在低(0.03%)和中等(0.01%)细胞遗传学风险组的患者中不同.
结论：我们的数据表明，将临床危险因素与MFC-MRD测量相结合是降低强度方案中BCP-ALL儿童风险组分层的最有用工具。然而,该算法可以补充部分ImR组的细胞遗传学数据.
方法：纳入了485名非高危BCP-ALL患儿，这些患儿具有可用的细胞遗传学数据，并通过多色流式细胞术（MFC）在诱导末期（EOI）进行了MRD研究。所有患者均接受“ALL-MB2008”降低强度方案的标准风险（SR）中危（ImR）方案治疗。
结论：在所有研究组患者中，发现203具有低风险的细胞遗传学（ETV6::RUNX1或高超二倍体），而其余282名儿童被归类为中等细胞遗传学风险组。对于具有有利和中等风险细胞遗传学的患者，MFC-MRD值的最显著阈值不同:分别为0.03%和0.04%.然而，临床定义的SR和ImR组的最有意义的阈值不同.对于SR组，无论是否存在/不存在有利的遗传病变，MFC-MRD阈值为0.1%是最具临床价值的，尽管ImR组的信息最丰富的阈值在低(0.03%)和中等(0.01%)细胞遗传学风险组的患者中不同.
结论：我们的数据表明，将临床危险因素与MFC-MRD测量相结合是降低强度方案中BCP-ALL儿童风险组分层的最有用工具。然而,该算法可以补充部分ImR组的细胞遗传学数据.
