Pre-emptive detection and evolution of relapse in acute myeloid leukemia by flow cytometric measurable residual disease surveillance.

Measurable residual disease (MRD) surveillance in acute myeloid leukemia (AML) may identify patients destined for relapse and thus provide the option of pre-emptive therapy to improve their outcome. Whilst flow cytometric MRD (Flow-MRD) can be applied to high-risk AML/ myelodysplasia patients, its diagnostic performance for detecting impending relapse is unknown. We evaluated this in a cohort comprising 136 true positives (bone marrows preceding relapse by a median of 2.45 months) and 155 true negatives (bone marrows during sustained remission). At an optimal Flow-MRD threshold of 0.040%, clinical sensitivity and specificity for relapse was 74% and 87% respectively (51% and 98% for Flow-MRD ≥ 0.1%) by 'different-from-normal' analysis. Median relapse kinetics were 0.78 log10/month but significantly higher at 0.92 log10/month for FLT3-mutated AML. Computational (unsupervised) Flow-MRD (C-Flow-MRD) generated optimal MRD thresholds of 0.036% and 0.082% with equivalent clinical sensitivity to standard analysis. C-Flow-MRD-identified aberrancies in HLADRlow or CD34+CD38low (LSC-type) subpopulations contributed the greatest clinical accuracy (56% sensitivity, 90% specificity) and notably, by longitudinal profiling expanded rapidly within blasts in > 40% of 86 paired MRD and relapse samples. In conclusion, flow MRD surveillance can detect MRD relapse in high risk AML and its evaluation may be enhanced by computational analysis.

Extreme weather events: Should drinking water quality management systems adapt to changing risk profiles?

Among the most widely predicted and accepted consequences of global climate change are increases in both the frequency and severity of a variety of extreme weather events. Such weather events include heavy rainfall and floods, cyclones, droughts, heatwaves, extreme cold, and wildfires, each of which can potentially impact drinking water quality by affecting water catchments, storage reservoirs, the performance of water treatment processes or the integrity of distribution systems. Drinking water guidelines, such as the Australian Drinking Water Guidelines and the World Health Organization Guidelines for Drinking-water Quality, provide guidance for the safe management of drinking water. These documents present principles and strategies for managing risks that may be posed to drinking water quality. While these principles and strategies are applicable to all types of water quality risks, very little specific attention has been paid to the management of extreme weather events. We present a review of recent literature on water quality impacts of extreme weather events and consider practical opportunities for improved guidance for water managers. We conclude that there is a case for an enhanced focus on the management of water quality impacts from extreme weather events in future revisions of water quality guidance documents.