Sources of error in measurement of minimal residual disease in childhood acute lymphoblastic leukemia.
AuthorLatham, S; Hughes, E; Budgen, B; Mechinaud, F; Crock, C; Ekert, H; Campbell, P; Morley, A
Source TitlePLoS One
PublisherPublic Library of Science (PLoS)
University of Melbourne Author/sCrock, Catherine
Document TypeJournal Article
CitationsLatham, S., Hughes, E., Budgen, B., Mechinaud, F., Crock, C., Ekert, H., Campbell, P. & Morley, A. (2017). Sources of error in measurement of minimal residual disease in childhood acute lymphoblastic leukemia.. PLoS One, 12 (10), pp.e0185556-. https://doi.org/10.1371/journal.pone.0185556.
Access StatusOpen Access
Open Access at PMChttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5626434
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.
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