Introduction: The aim of the study was to analyse the frequency of silent inactivation and allergic reaction to asparaginase (ASP) and its impact on treatment results in patients with lymphoblastic leukaemia.
Material And Methods: Seventy patients with acute lymphoblastic leukaemia treated with ASP were enrolled in the study. Asparaginase activity was monitored. The patients were switched to another ASP formulation after allergy or inactivation. The treatment results were analysed.
Results: Silent inactivation of native ASP was diagnosed in 5 patients (7%) and allergy in 34 patients (49%), and these patients were switched to pegylated ASP (PEG-ASP). Silent inactivation of PEG-ASP occurred in 8 patients (23%) and allergy in 6 patients (17%). Eight children continued therapy with Erwinase, and 4 did not switch to Erwinase after inactivation of PEG-ASP. Allergy to Erwinase occurred in 2 patients (22%); there was no inactivation. No significant differences in outcome were found between the groups of patients with and without allergy or silent inactivation of ASP. Due to regular monitoring and switching to other ASP preparations after allergy or silent inactivation, therapeutic activity was ensured in almost all patients.
Conclusions: Monitoring of ASP activity is crucial to recognize silent inactivation and to guarantee treatment effectiveness by switching to other ASP preparations.
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http://dx.doi.org/10.5114/wo.2023.124972 | DOI Listing |
Curr Med Chem
January 2025
3rd Department of Cardiology, General Hospital of Thoracic Diseases 'Sotiria', National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.
Arterial hypertension is a silent and progressive disease with deleterious vascular implications on all target organs, including the heart, the brain, the kidneys, and the eyes. Oxidative stress, defined as the overproduction of Reactive Oxygen Species (ROS) over antioxidants, is capable of deteriorating not only the normal endothelial but also the cellular function with further cardiovascular implications. Xanthine oxidase activity, NADPH oxidase overexpression, and ROS production lead to hypertension and high arterial tone, culminating in end-organ damage.
View Article and Find Full Text PDFJ Evol Biol
December 2024
Department of Biology, Georgetown University, 37th and O Streets NW, Washington DC.
In eutherians, one of the X chromosomes in each cell of the early female embryo is rendered transcriptionally silent through X chromosome inactivation. The choice of which X chromosome to inactivate takes place independently in each cell and is stably inherited through development, leading to a roughly 50:50 ratio of cells in the adult body expressing one or the other X chromosome. However, X chromosome inactivation can be skewed, with certain X chromosomes showing a heritable tendency to avoid inactivation.
View Article and Find Full Text PDFBlood Adv
January 2025
Department of Pediatrics and the Ben Towne Center for Childhood Cancer Research, Seattle Children's Hospital, University of Washington, Seattle, WA.
Children's Oncology Group study AALL1931 investigated the efficacy and safety of recombinant Erwinia asparaginase (JZP458) in patients with acute lymphoblastic leukemia/lymphoblastic lymphoma and hypersensitivity reactions/silent inactivation to Escherichia coli-derived asparaginases. Each pegylated Escherichia coli asparaginase dose remaining in a patient's treatment plan was replaced by intramuscular (IM) or IV JZP458 (6 doses) administered Monday/Wednesday/Friday (MWF). Three IM cohorts (1a [25 mg/m2 MWF], n = 33; 1b [37.
View Article and Find Full Text PDFDiagnostics (Basel)
October 2024
Luton & Dunstable University Hospital, Lewsey Road, Luton LU4 0DZ, UK.
The diaphragm is the primary muscle of respiration. Here, we disclose a fascinating patient's perspective that led, by clinical reasoning alone, to a novel mechanism of spontaneous respiratory arrests termed diaphragm cramp-contracture (DCC). Although the 7-year-old boy survived its paroxysmal nocturnal "bearhug pain apnea" episodes, essentially by breathing out to breathe in, DCC could cause sudden unexpected deaths in children, especially infants.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2025
Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, College of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, China.
Granzyme A (GzmA) secreted by natural killer (NK) cells has garnered considerable interest as a biomarker to evaluate the efficacy of cancer immunotherapy. However, current methodologies to selectively monitor the spatial distribution of GzmA in cancer cells during NK cell-targeted therapy are extremely challenging, primarily due to the existence of diverse cell populations, the low levels of GzmA expression, and the limited availability of GzmA probes. Herein we develop a multi-modular, structurally-ordered DNA nanodevice for evaluating NK cell-mediated cancer immunotherapy (MODERN), that permits spatioselective imaging of GzmA in cancer cells through GzmA-induced apurinic/apyrimidinic endonuclease 1 (APE1) inactivation.
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