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1 December 2017
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Neurologic adverse events induced by autologous transfer of CD19-targeted chimeric antigen receptor-modified T (CAR-T) cells were investigated in 133 patients with B-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, or non-Hodgkin lymphoma who had received chemotherapy and CD19 CAR-T cell infusion. Cytokine release syndrome (CRS) preceded neurotoxicity in all 28 patients who developed grade 3+ neurotoxicity, and severe neurotoxicity was linked to endothelial activation and increased blood–brain barrier permeability. Signs of endothelial activation and vascular disruption were observed in the brain of a patient who died of CRS-induced neurotoxicity, and endothelial activation prior to treatment was linked to an increased risk of high-grade neurotoxicity. Altogether, these results identify risk factors for CD19 CAR-T cell therapy–induced neurotoxicity, and suggest that endothelial activation may serve as a biomarker for severe neurotoxicity. For details, please see the article by Gust, Hay, Hanafi, and colleagues on page 1404. - PDF Icon PDF LinkTable of Contents
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ISSN 2159-8274
EISSN 2159-8290
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Early Detection of Molecular Residual Disease in Localized Lung Cancer by Circulating Tumor DNA Profiling
Aadel A. Chaudhuri; Jacob J. Chabon; Alexander F. Lovejoy; Aaron M. Newman; Henning Stehr; Tej D. Azad; Michael S. Khodadoust; Mohammad Shahrokh Esfahani; Chih Long Liu; Li Zhou; Florian Scherer; David M. Kurtz; Carmen Say; Justin N. Carter; David J. Merriott; Jonathan C. Dudley; Michael S. Binkley; Leslie Modlin; Sukhmani K. Padda; Michael F. Gensheimer; Robert B. West; Joseph B. Shrager; Joel W. Neal; Heather A. Wakelee; Billy W. Loo, Jr; Ash A. Alizadeh; Maximilian Diehn
Research Articles
Endothelial Activation and Blood–Brain Barrier Disruption in Neurotoxicity after Adoptive Immunotherapy with CD19 CAR-T Cells
Juliane Gust; Kevin A. Hay; Laïla-Aïcha Hanafi; Daniel Li; David Myerson; Luis F. Gonzalez-Cuyar; Cecilia Yeung; W. Conrad Liles; Mark Wurfel; Jose A. Lopez; Junmei Chen; Dominic Chung; Susanna Harju-Baker; Tahsin Özpolat; Kathleen R. Fink; Stanley R. Riddell; David G. Maloney; Cameron J. Turtle
Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer
Scott Gettinger; Jungmin Choi; Katherine Hastings; Anna Truini; Ila Datar; Ryan Sowell; Anna Wurtz; Weilai Dong; Guoping Cai; Mary Ann Melnick; Victor Y. Du; Joseph Schlessinger; Sarah B. Goldberg; Anne Chiang; Miguel F. Sanmamed; Ignacio Melero; Jackeline Agorreta; Luis M. Montuenga; Richard Lifton; Soldano Ferrone; Paula Kavathas; David L. Rimm; Susan M. Kaech; Kurt Schalper; Roy S. Herbst; Katerina Politi
Author Choice
mTOR and HDAC Inhibitors Converge on the TXNIP/Thioredoxin Pathway to Cause Catastrophic Oxidative Stress and Regression of RAS-Driven Tumors
Clare F. Malone; Chloe Emerson; Rachel Ingraham; William Barbosa; Stephanie Guerra; Haejin Yoon; Lin L. Liu; Franziska Michor; Marcia Haigis; Kay F. Macleod; Ophélia Maertens; Karen Cichowski
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