Adverse effects of pegaspargase in pediatric patients receiving doses greater than 3,750 IU

BackgroundIncreased toxicities have been identified with higher doses of pegaspargase (PEG‐ASP) in adults. This has led to routine use of a dose cap of 3,750 IU for adult acute lymphoblastic leukemia (ALL) patients in most institutions. In pediatric ALL patients, PEG‐ASP is not capped. There is concern at our institution that larger doses may result in increased rates of adverse effects and that increased monitoring may be warranted in pediatric patients receiving doses greater than 3,750 IU. The objective of this study is to quantify the difference in the rates of PEG‐ASP‐associated adverse events between pediatric patients who received doses greater than 3,750 IU and less than or equal to 3,750 IU.MethodsRetrospective chart review of patients 1–21 years old with pre‐B‐cell ALL who received PEG‐ASP between 2007 and 2014 at an academic medical center.ResultsOf 183 patients included in the analysis, 24 received PEG‐ASP doses higher than 3,750 IU and 159 received doses less than or equal to 3,750 IU. The incidence of venous thromboembolism (VTE) was significantly higher for patients in the group that received more than 3,750 IU compared with those who received 3,750 IU or less (20.8 vs. 1.89%, respectively; P = 0.0011). The incidence of pancreatitis (P = 0.0306) and hyperglycemia (P = 0.0089) were also higher in the group that received more than 3,750 IU.ConclusionsPEG‐ASP doses higher than 3,750 IU are associated with higher rates of VTE, pancreatitis, and hyperglycemia in pediatric patients with pre‐B‐cell ALL. Patients receiving more than 3,750 IU should have increased monitoring, and larger, multicenter trials are needed to determine if monitoring, VTE prophylaxis, and potential dose capping recommendations should be added to clinical trial protocols.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138220/1/pbc26555_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138220/2/pbc26555.pd

Think Again – Supplying War: Reappraising Military Logistics and Its Centrality to Strategy and War

This article argues that logistics constrains strategic opportunity while itself being heavily circumscribed by strategic and operational planning. With the academic literature all but ignoring the centrality of logistics to strategy and war, this article argues for a reappraisal of the critical role of military logistics, and posits that the study and conduct of war and strategy are incomplete at best or false at worst when they ignore this crucial component of the art of war. The article conceptualises the logistics–strategy nexus in a novel way, explores its contemporary manifestation in an age of uncertainty, and applies it to a detailed case study of UK operations in Iraq and Afghanistan since 2001