{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:15:47Z","timestamp":1787026547286,"version":"build-2736575974"},"reference-count":14,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T00:00:00Z","timestamp":1767312000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To assess the safety profile of administering intrathecal (IT) chemotherapy concurrently with blinatumomab in pediatric patients with acute lymphoblastic leukemia (ALL).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective analysis included 93 pediatric ALL patients treated between February 2021 and May 2025 who received blinatumomab.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of the 93 enrolled patients (median [Q1, Q3] age, 6 [4, 12] years), 42 (45%) were given IT chemotherapy concurrently, while the remaining 51 (55%) served as controls. Neurotoxic events occurred in eight patients (8.8%) overall, with no statistically significant difference between the concurrent IT and control groups (12% vs. 6%, p = 0.461). However, receiving IT chemotherapy on Day 1 of blinatumomab was strongly associated with neurotoxicity (OR = 15.6; 95% CI: 2.96\u201387.8; p = 0.001). Additional univariate predictors included CD4+ T-cell count (OR = 0.03; 95% CI: 0.00\u20130.50; p = 0.045), serum albumin (OR = 1.17; 95% CI: 1.02\u20131.39; p = 0.042), and bone marrow blast percentage (OR = 1.05; 95% CI: 1.01\u20131.09; p = 0.017). Multivariate analysis identified Day 1 concurrent IT administration as an independent risk factor (OR = 12.5; 95% CI: 1.45\u2013131; p = 0.023).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Initiating IT chemotherapy on the same day as blinatumomab infusion significantly increases the risk of neurotoxicity in pediatric ALL patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1690916","type":"journal-article","created":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T06:28:33Z","timestamp":1767335313000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The timing of concurrent intrathecal chemotherapy during blinatumomab infusion influences neurotoxicity in pediatric acute lymphoblastic leukemia"],"prefix":"10.3389","volume":"16","author":[{"given":"Bingju","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunpeng","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liying","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guotao","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.33967","article-title":"Extramedullary disease relapse and progression after blinatumomab therapy for treatment of acute lymphoblastic leukemia","volume":"128","author":"Aldoss","year":"2022","journal-title":"Cancer"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2018.12.758","article-title":"ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells","volume":"25","author":"Lee","year":"2019","journal-title":"Biol Blood Marrow Transplant"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2022.2090555","article-title":"The safety of concurrent intrathecal chemotherapy during blinatumomab in adults with acute lymphoblastic leukemia","volume":"63","author":"Ngo","year":"2022","journal-title":"Leuk Lymphoma"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26880","article-title":"Timing of intrathecal chemotherapy and blinatumomab impacts neurotoxicity in acute lymphoblastic leukemia","volume":"98","author":"Lee","year":"2023","journal-title":"Am J Hematol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-99-117400","article-title":"Safety and efficacy of blinatumomab in patients with central nervous system (CNS) disease: A single institution experience","volume":"132","author":"Alfayez","year":"2018","journal-title":"Blood"},{"key":"B6","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1186\/s12916-025-03913-6","article-title":"Adverse events in the nervous system associated with blinatumomab: a real-world study","volume":"23","author":"Gao","year":"2025","journal-title":"BMC Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1080\/14740338.2017.1338270","article-title":"Clinical applications and safety evaluation of the new CD19 specific T-cell engager antibody construct blinatumomab","volume":"16","author":"Wilke","year":"2017","journal-title":"Expert Opin Drug Saf"},{"key":"B8","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1158\/0008-5472.CAN-19-1131","article-title":"Adhesion of T cells to endothelial cells facilitates blinatumomab-associated neurologic adverse events","volume":"80","author":"Klinger","year":"2020","journal-title":"Cancer Res"},{"key":"B9","doi-asserted-by":"publisher","first-page":"101254","DOI":"10.1016\/j.blre.2024.101254","article-title":"Neuro-toxicities of chemo- and immune-therapies in haematologic Malignancies: from mechanism to management","volume":"69","author":"Klinger","year":"2025","journal-title":"Blood Rev"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2024-333924","article-title":"Neurotoxic complications of chimeric antigen receptor (CAR) T-cell therapy","volume":"96","author":"Vonberg","year":"2025","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"B11","doi-asserted-by":"publisher","first-page":"103285","DOI":"10.1016\/j.retram.2021.103285","article-title":"The use of intrathecal chemotherapy and dexamethasone for secondary prevention of blinatumomab-related neurotoxicity","volume":"69","author":"Aqel","year":"2021","journal-title":"Curr Res Transl Med"},{"key":"B12","unstructured":"Intrathecal chemoprophylaxis to prevent neurotoxicity associated with blinatumomab therapy for acute lymphoblastic leukemia\n          \n          \n          ClinicalTrials.gov identifier NCT05519579\n          \n          2022"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1609783","article-title":"Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia","volume":"376","author":"Kantarjian","year":"2017","journal-title":"N Engl J Med"},{"key":"B14","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/S1470-2045(14)71170-2","article-title":"Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study","volume":"16","author":"Topp","year":"2015","journal-title":"Lancet Oncol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1690916\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T06:28:34Z","timestamp":1767335314000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1690916\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,2]]},"references-count":14,"alternative-id":["10.3389\/fimmu.2025.1690916"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1690916","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,2]]},"article-number":"1690916"}}