Aims and backgroundWhole-genome sequencing (WGS) is increasingly applied in clinical practice and expected to replace standard-of-care (SoC) genetic diagnostics in hematological malignancies. This study aims to assess and compare the fully burdened cost ('micro-costing') per patient for Swedish laboratories using WGS and SoC, respectively, in pediatric and adult patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).MethodsThe resource use and cost details associated with SoC, e.g. chromosome banding analysis, fluorescent in situ hybridization, and targeted sequencing analysis, were collected via activity-based costing methods from four diagnostic laboratories. For WGS, corresponding data was collected from two of the centers. A simulation-based scenario model was developed for analyzing the WGS cost based on different annual sample throughput to evaluate economy of scale.ResultsThe average SoC total cost per patient was <euro>2,465 for pediatric AML and <euro>2,201 for pediatric ALL, while in adults, the corresponding cost was <euro>2,458 for AML and <euro>1,207 for ALL. The average WGS cost (90x tumor/30x normal; sequenced on the Illumina NovaSeq 6000 platform) was estimated to <euro>3,472 based on an annual throughput of 2,500 analyses, however, with an annual volume of 7,500 analyses the average cost would decrease by 23% to <euro>2,671.ConclusionIn summary, WGS is currently more costly than SoC, however the cost can be reduced by utilizing laboratories with higher throughput and by the expected decline in cost of reagents. Our data provides guidance to decision-makers for the resource allocation needed when implementing WGS in diagnostics of hematological malignancies.