Prediction of attributable mortality in pediatric patients with cancer admitted to the intensive care unit for suspected infection: A comprehensive evaluation of risk scores

Abstract Objective To evaluate the performance of existing sepsis scores for prediction of adverse outcomes in children with cancer admitted to the ICU with suspected sepsis. Design Retrospective chart review using data available at 1, 6, 12, and 24 h after ICU admission to calculate the Pediatric Risk of Mortality 3 (PRISM‐3), Pediatric Sequential Organ Failure Assessment (pSOFA), Paediatric Logistic Organ Dysfunction 2 (PELOD‐2), and Quick Pediatric Sequential Organ Failure Assessment (qSOFA) scores. Area under the receiver operator characteristic curve (AUROC) was used to evaluate performance for prediction of attributable mortality. Sensitivity analyses included recalculation of scores using worst preceding values for each variable, excluding hematologic parameters, and prediction of alternative outcomes. Setting St. Jude Children's Research Hospital, a pediatric comprehensive cancer center in the USA. Patients Pediatric patients (<25 years of age) receiving conventional therapy for cancer admitted to the ICU with suspected sepsis between 2013 and 2019. Results Of 207 included episodes of suspected sepsis, attributable mortality was 16 (7.7%) and all evaluated sepsis scores performed poorly (maximal AUROC of 0.73 for qSOFA at 1 and 24 h). Sensitivity analyses did not identify an alternative approach that significantly improved prediction. Conclusions Currently available sepsis scores perform poorly for prediction of attributable mortality in children with cancer who present to ICU with suspected sepsis. More research is needed to identify reliable predictors of adverse outcomes in this population

The genomic landscape of core-binding factor acute myeloid leukemias

Acute myeloid leukemia (AML) comprises a heterogeneous group of leukemias frequently defined by recurrent cytogenetic abnormalities, including rearrangements involving the core-binding factor (CBF) transcriptional complex. To better understand the genomic landscape of CBF-AMLs, we analyzed both pediatric (n = 87) and adult (n = 78) samples, including cases with RUNX1-RUNX1T1 (n = 85) or CBFB-MYH11 (n = 80) rearrangements, by whole-genome or whole-exome sequencing. In addition to known mutations in the Ras pathway, we identified recurrent stabilizing mutations in CCND2, suggesting a previously unappreciated cooperating pathway in CBF-AML. Outside of signaling alterations, RUNX1-RUNX1T1 and CBFB-MYH11 AMLs demonstrated remarkably different spectra of cooperating mutations, as RUNX1-RUNX1T1 cases harbored recurrent mutations in DHX15 and ZBTB7A, as well as an enrichment of mutations in epigenetic regulators, including ASXL2 and the cohesin complex. This detailed analysis provides insights into the pathogenesis and development of CBF-AML, while highlighting dramatic differences in the landscapes of cooperating mutations for these related AML subtypes