Safety and Efficacy of Chimeric Antigen Receptor T-Cell Therapy in Children With Central Nervous System Leukemia |
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| Authors: | Lin Zhang Yingxi Zuo Aidong Lu Jun Wu Yueping Jia Yu Wang Leping Zhang |
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| Institution: | 1. Department of Pediatrics, Peking University People’s Hospital, Beijing, China;2. Research Department, Immunotech Applied Science Ltd, Beijing, China;1. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX;2. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX;3. Georgia Cancer Center, Augusta, GA;1. Department of Oncology, University of Torino, Torino, Italy;2. Medical Physics Unit, A.O.U. Città della Salute e della Scienza, Torino, Italy;3. Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino/AOU “Città della Salute e della Scienza di Torino”, Torino, Italy;4. Department of Medical Sciences, Pathology Unit, Città della Salute e della Scienza Hospital, University of Torino, Torino, Italy;1. Adult Hematology and Stem Cell Transplantation Department, King Fahad Specialist Hospital, Dammam, Saudi Arabia;2. Radiation Oncology Department, King Fahad Specialist Hospital, Dammam, Saudi Arabia;3. Department of Pathology and Laboratory Medicine, King Fahad Specialist Hospital, Dammam, Saudi Arabia;4. Department of Medical Imaging, King Fahad Specialist Hospital, Dammam, Saudi Arabia;1. Hans Messner Allogeneic Transplant Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada;2. Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, Ontario, Canada |
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| Abstract: | Backgroundchimeric 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 MethodsWe 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.ResultsAfter 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.ConclusionCAR-T infusion is a potentially effective treatment for relapsed/refractory B-ALL patients with central nervous system involvement. |
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| Keywords: | B-cell acute lymphoblastic leukemia CAR-T-related encephalopathy sydrome Cytokine release syndrome Neurotoxicity Pediatric |
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