Latham Sue, Hughes Elizabeth, Budgen Bradley, Mechinaud Francoise, Crock Catherine, Ekert Henry, Campbell Peter, Morley Alexander
Department of Haematology and Genetic Pathology, Flinders University and Medical Centre, Bedford Park, SA, Australia.
Childrens Cancer Centre, The Royal Childrens Hospital, Parkville Vic, Australia.
PLoS One. 2017 Oct 3;12(10):e0185556. doi: 10.1371/journal.pone.0185556. eCollection 2017.
The level of minimal residual disease (MRD) in marrow predicts outcome and guides treatment in childhood acute lymphoblastic leukemia (ALL) but accurate prediction depends on accurate measurement.
Forty-one children with ALL were studied at the end of induction. Two samples were obtained from each iliac spine and each sample was assayed twice. Assay, sample and side-to-side variation were quantified by analysis of variance and presumptively incorrect decisions related to high-risk disease were determined using the result from each MRD assay, the mean MRD in the patient as the measure of the true value, and each of 3 different MRD cut-off levels which have been used for making decisions on treatment.
Variation between assays, samples and sides each differed significantly from zero and the overall standard deviation for a single MRD estimation was 0.60 logs. Multifocal residual disease seemed to be at least partly responsible for the variation between samples. Decision errors occurred at a frequency of 13-14% when the mean patient MRD was between 10-2 and 10-5. Decision errors were observed only for an MRD result within 1 log of the cut-off value used for assessing high risk. Depending on the cut-off used, 31-40% of MRD results were within 1 log of the cut-off value and 21-16% of such results would have resulted in a decision error.
When the result obtained for the level of MRD is within 1 log of the cut-off value used for making decisions, variation in the assay and/or sampling may result in a misleading assessment of the true level of marrow MRD. This may lead to an incorrect decision on treatment.
骨髓中微小残留病（MRD）水平可预测儿童急性淋巴细胞白血病（ALL）的预后并指导治疗，但准确的预测依赖于准确的测量。
对41例ALL患儿在诱导治疗结束时进行研究。从每个髂棘获取两个样本，每个样本进行两次检测。通过方差分析对检测、样本和双侧差异进行量化，并使用每个MRD检测结果、患者的平均MRD作为真实值的度量以及用于做出治疗决策的3个不同MRD临界值中的每一个，来确定与高危疾病相关的推定错误决策。
检测之间、样本之间和双侧之间的差异均显著不为零，单个MRD估计的总体标准差为0.60对数。多灶性残留病似乎至少部分是样本间差异的原因。当患者平均MRD在10⁻²至10⁻⁵之间时，决策错误的发生频率为13% - 14%。仅在用于评估高危的临界值1对数范围内的MRD结果中观察到决策错误。根据所使用的临界值，31% - 40%的MRD结果在临界值1对数范围内，其中21% - 16%的此类结果会导致决策错误。
当获得的MRD水平结果在用于决策的临界值1对数范围内时，检测和/或采样的差异可能导致对骨髓MRD真实水平的误导性评估。这可能导致治疗决策错误。
