Background: chimeric antigen receptor-modified T cell (CAR-T) therapy is an effective and promising treatment for refractory and multiply relapsed B-cell acute lymphoblastic leukemia (B-ALL). Because of its side effects and poor responses such as neurotoxicity and cytokine release syndrome, patients with central nervous system leukemia were excluded in most previous clinical trials of CAR-T treatment.
Patients And Methods: We enrolled 3 B-ALL patients with central nervous system leukemia relapse. They were infused with CD19-specific CAR-Ts, and their clinical responses were evaluated by bone marrow smear, flow cytometry, and cytogenetic alterations detected by quantitative PCR, interleukin-6, and the expansion and persistence of circulating CAR-Ts in peripheral blood and cerebrospinal fluid.
Results: After CAR-T infusion, 2 of the 3 patients experienced bone marrow minimal residual disease-negative complete remission, and all patients tested negative for residual leukemia cells in cerebrospinal fluid tested by flow cytometry. These 3 patients experienced grade 2 or 3 cytokine release syndrome, which resolved completely after symptomatic treatment. None experienced neurotoxicity or needed further intensive care.
Conclusion: CAR-T infusion is a potentially effective treatment for relapsed/refractory B-ALL patients with central nervous system involvement.
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http://dx.doi.org/10.1016/j.clml.2020.12.009 | DOI Listing |
Am J Trop Med Hyg
January 2025
Department of Environmental Biology & Medical Parasitology, Hanyang University College of Medicine, Seoul, Republic of Korea.
Neurocysticercosis, a central nervous system infection caused by the zoonotic parasite Taenia solium, is a leading cause of acquired epilepsy worldwide. It is common in areas with extensive pig farming and pork consumption. This report presents an unusual case of neurocysticercosis in a 28-year-old male from Timor-Leste, a region of nonendemicity for human cases of Taenia solium.
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen DK-2100, Denmark.
GABA receptors (GABARs) are the major elements of inhibitory neurotransmission in the central nervous system (CNS). They are established targets for regulation by endogenous brain neuroactive steroids (NASs) such as pregnanolone. However, the complexity of de novo synthesis of NAS derivatives has hindered attempts to circumvent the principal limitations of using endogenous NASs, including selectivity and limited oral bioavailability.
View Article and Find Full Text PDFNeurosurgery
September 2024
Department of Surgery, Division of Neurosurgery, Centre de recherche du Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, Sherbrooke, Québec, Canada.
Background And Objectives: Oligodendrogliomas are primary brain tumors classified as isocitrate deshydrogenase-mutant and 1p19q codeleted in the 2021 World Health Organization Classification of central nervous system tumors. Surgical resection, radiotherapy, and chemotherapy are well-established management options for these tumors. Few studies have evaluated the efficacy of stereotactic radiosurgery (SRS) for oligodendroglioma.
View Article and Find Full Text PDFNeurotox Res
January 2025
Molecular Neuropsychiatry Section, Intramural Research Program, NIH/ NIDA, 21224, Baltimore, MD, U.S.A.
To identify factors involved in methamphetamine (METH) neurotoxicity, we comprehensively searched for genes which were differentially expressed in mouse striatum after METH administration using differential display (DD) reverse transcription-PCR method and sequent single-strand conformation polymorphism analysis, and found two DD cDNA fragments later identified as mRNA of Nedd4 (neural precursor cell expressed developmentally downregulated 4) WW domain-binding protein 5 (N4WBP5), later named Nedd4 family-interacting protein 1 (Ndfip1). It is an adaptor protein for the binding between Nedd4 of ubiquitin ligase (E3) and target substrate protein for ubiquitination. Northern blot analysis confirmed drastic increases in Ndfip1 mRNA in the striatum after METH injections, and in situ hybridization histochemistry showed that the mRNA expression was increased in the hippocampus and cerebellum at 2 h-2 days, in the cerebral cortex and striatum at 18 h-2 days after single METH administration.
View Article and Find Full Text PDFMetab Brain Dis
January 2025
Section of Osteimmunology and Oral Immunology, Laboratory of Dental Reseach. FES Iztacala, National Autonomous University of Mexico (UNAM), México, Mexico State, México.
Unlabelled: LCN2 has an osteokine important for appetite regulation; in type 2 diabetes (T2D) it is not known whether appetite regulation mediated by LCN2 in the brain is altered. In this work, we focus on exploring the role of blocking LCN2 in metabolic health and appetite regulation within the central nervous system of mice with T2D.
Material And Methods: 4-week-old male C57BL/6 mice were used, divided into four experimental groups: intact, T2D, TD2/anti-LCN2, and T2D/IgG as isotype control.
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