eprintid: 10145152 rev_number: 7 eprint_status: archive userid: 699 dir: disk0/10/14/51/52 datestamp: 2022-03-16 11:30:41 lastmod: 2022-03-16 11:30:41 status_changed: 2022-03-16 11:30:41 type: article metadata_visibility: show sword_depositor: 699 creators_name: Cooray, S creators_name: Sabanathan, S creators_name: Hacohen, Y creators_name: Worth, A creators_name: Eleftheriou, D creators_name: Hemingway, C title: Treatment Strategies for Central Nervous System Effects in Primary and Secondary Haemophagocytic Lymphohistiocytosis in Children ispublished: inpress divisions: C07 divisions: F87 divisions: B02 divisions: UCL divisions: D07 note: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. abstract: Purpose of Review: This review presents an appraisal of current therapeutic options for the treatment of central nervous system haemophagocytic lymphohistiocytosis (CNS-HLH) in the context of systemic disease, as well as when CNS features occur in isolation. We present the reader with a diagnostic approach to CNS-HLH and commonly used treatment protocols. We discuss and evaluate newer treatments on the horizon. Recent Findings: Mortality is high in patients who do not undergo HSCT, and while larger studies are required to establish benefit in many treatments, a number of new treatments are currently being evaluated. Alemtuzumab is being used as a first-line treatment for CNS-HLH in a phase I/II multicentre prospective clinical trial as an alternative to traditional HLH-1994 and 2004 protocols. It has also been used successfully as a second-line agent for the treatment of isolated CNS-HLH that is refractory to standard treatment. Ruxolitinib and emapalumab are new immunotherapies that block the Janus kinase—Signal Transducer and Activator of Transcription (JAK-STAT) pathway that have shown efficacy in refractory HLH, including for CNS-HLH disease. Summary: Treatment of CNS-HLH often requires HLH-94 or 2004 protocols followed by haematopoietic stem cell transplantation (HSCT) to maintain remission, although relapse can occur, particularly with reduced intensity conditioning if donor chimerism falls. CNS features have been shown to improve or stabilise following HSCT in CNS-HLH in the context of systemic disease and in isolated CNS-HLH. Encouraging reports of early cohort studies suggest alemtuzumab and the Janus kinase (JAK) inhibitor ruxolitinib offer potential salvage therapy for relapsed and refractory CNS-HLH. Newer immunotherapies such as tocilizumab and natalizumab have been shown to be beneficial in sporadic cases. CNS-HLH due to primary gene defects may be amenable to gene therapy in the future. date: 2022-03-04 date_type: published publisher: Springer Science and Business Media LLC official_url: https://doi.org/10.1007/s11940-022-00705-8 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1944679 doi: 10.1007/s11940-022-00705-8 lyricists_name: Hacohen, Yael lyricists_id: YHACO24 actors_name: Kalinowski, Damian actors_id: DKALI47 actors_role: owner full_text_status: public publication: Current Treatment Options in Neurology issn: 1092-8480 citation: Cooray, S; Sabanathan, S; Hacohen, Y; Worth, A; Eleftheriou, D; Hemingway, C; (2022) Treatment Strategies for Central Nervous System Effects in Primary and Secondary Haemophagocytic Lymphohistiocytosis in Children. Current Treatment Options in Neurology 10.1007/s11940-022-00705-8 <https://doi.org/10.1007/s11940-022-00705-8>. (In press). Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10145152/1/Hacohen_Treatment%20Strategies%20for%20Central%20Nervous%20System%20Effects%20in%20Primary%20and%20Secondary%20Haemophagocytic%20Lymphohistiocytosis%20in%20Children_AOP.pdf