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ABSTRACT: Introduction
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.Methods
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.Results
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.Conclusion
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.
SUBMITTER: Latham S
PROVIDER: S-EPMC5626434 | biostudies-literature | 2017
REPOSITORIES: biostudies-literature
Latham Sue S Hughes Elizabeth E Budgen Bradley B Mechinaud Francoise F Crock Catherine C Ekert Henry H Campbell Peter P Morley Alexander A
PloS one 20171003 10
<h4>Introduction</h4>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.<h4>Methods</h4>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 ...[more]