Sources of error in measurement of minimal residual disease in childhood acute lymphoblastic leukemia.

Autor: Latham S; Department of Haematology and Genetic Pathology, Flinders University and Medical Centre, Bedford Park, SA, Australia., Hughes E; Department of Haematology and Genetic Pathology, Flinders University and Medical Centre, Bedford Park, SA, Australia., Budgen B; Department of Haematology and Genetic Pathology, Flinders University and Medical Centre, Bedford Park, SA, Australia., Mechinaud F; Childrens Cancer Centre, The Royal Childrens Hospital, Parkville Vic, Australia., Crock C; Clinical Haematology Department, The Royal Childrens Hospital, Parkville Vic, Australia., Ekert H; Childrens Cancer Centre, The Royal Childrens Hospital, Parkville Vic, Australia., Campbell P; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, United Kingdom., Morley A; Department of Haematology and Genetic Pathology, Flinders University and Medical Centre, Bedford Park, SA, Australia.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2017 Oct 03; Vol. 12 (10), pp. e0185556. Date of Electronic Publication: 2017 Oct 03 (Print Publication: 2017).
DOI: 10.1371/journal.pone.0185556
Abstrakt: 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.
Databáze: MEDLINE