Have we been qualifying measurable residual disease correctly?

Abstract

Someone told me that each equation I included in the book would halve the sales. I therefore resolved not to have any equations at all. In the end, however, I did put in one equation, Einstein's famous equation, E = m c squared. I hope that this will not scare off half of my potential readers.

Gene expression prognostic of early relapse risk in low‐risk B‐cell acute lymphoblastic leukaemia in children

“…All subjects in Discovery Cohort had MRD‐test data 19 and 46 days after therapy started [ 35 ]. MRD was quantified by multi‐parameter flow cytometry (MPFC; BD FACSCanto Plus flow cytometer [V657338000225; BD Biosciences] with BD FACSDiva Software v8.0.1) analyses of bone marrow samples using antibodies to CD19 (PE‐Cy7 IM3628; Beckman Coulter, Brea, CA, USA), CD10 (PE A07760; Beckman Coulter), CD34 (PerCP‐Cy5.5 343522; BioLegend), CD20 (APC‐H7 641396; BD Biosciences), CD22 (BV421 302524; BioLegend), CD38 (FITC A07778; Beckman Coulter), CD45 (V500 662912; BD Biosciences) and CD81 (APC 551112; BD Biosciences).…”

“…All subjects in Discovery Cohort had MRD-test data 19 and 46 days after therapy started[35]. MRD was quantified by TA B L E 1…”

Measurable residual disease (MRD)-testing in haematological and solid cancers

“…Even without spatial heterogeneity there is Poisson noise. The number of leukaemia cells in a 5 ml sample from a 5 L blood volume fluctuates as a result of Poisson noise alone and taking this into account improves interpretation of MRD tests [ 141 , 142 ]. With the proviso you have a sensitive and specific assay, cell-free detection of ctDNA in solid cancers might be less susceptible to Poisson noise than other MRD-testing assays that rely on presence of intact cancer cells in a sample (e.g.…”

“…Guidelines for MPFC-based MRD-testing often recommend declaring a test positive only if ≥5 × 10E+5 cells are analysed and if ≥20 or ≥50 cells are positive [ 14 , 78 , 151 ]. Adopting these guidelines decreases false-positives but increases false-negatives [ 141 , 152 ]. Using fusion gene transcript concentration as a proxy for numbers of residual cancer cells implicitly assumes all cancer cells have equal transcription rates.…”

Response to comment on Have we been qualifying measurable residual disease correctly?

“…Professor Morley was correct in pointing out in our Perspective we focused on analysis of Poisson noise, a type of sampling error [ 1 ]. Indeed, it is sometimes useful to distinguish between errors in sampling cells from a sub-population and errors in sampling a sub-population from the entire population of cells.…”