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The report describes a 63-year-old man with relapsed CLL after early discontinuation of ibrutinib due to intolerance, followed by obinutuzumab plus venetoclax achieving undetectable MRD before CNS relapse. He presented with confusion and abnormal MRI and CSF findings, then received zanubrutinib 320 mg daily. Rapid cognitive improvement and complete CNS resolution were documented on serial MRI and repeat lumbar puncture, with sustained remission over six months and no significant adverse effects.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/successful-zanubrutinib-monotherapy-in-a-rare-cns-presentation-of-relapsed-cll-case-report/444215/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/successful-zanubrutinib-monotherapy-in-a-rare-cns-presentation-of-relapsed-cll-case-report/444215.png","ImageObject",300,407,{"name":92,"@type":93},"Terk","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-01","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"How rare is CNS involvement in chronic lymphocytic leukemia (CLL)?","Question",{"text":113,"@type":114},"CNS involvement occurs in less than 1% of CLL cases. It is described as an infrequent complication.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What were the key findings when the patient first presented?",{"text":118,"@type":114},"The patient had confusion and altered mental status. Brain MRI showed abnormal findings concerning leukemic infiltration, and lumbar puncture confirmed malignant CD5+ CLL cells in CSF.",{"name":120,"@type":111,"acceptedAnswer":121},"What outcome did zanubrutinib monotherapy achieve?",{"text":122,"@type":114},"After starting zanubrutinib 320 mg daily, the patient showed marked cognitive improvement within four weeks, followed by full resolution of CNS lesions by follow-up MRI and repeat lumbar puncture demonstrating CSF clearance of CLL cells. He remained in complete remission at six months with no significant adverse effects reported.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},444215,1790785563,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":24,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},1099525198933,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Wiley  \nCase Reports in Hematology  \nVolume 2026, Article ID 1150546, 5 pages [https://doi.org/10.1155/crh/1150546](https://doi.org/10.1155/crh/1150546)  \nCase Report  \nSuccessful Zanubrutinib Monotherapy in a Rare CNS Presentation of Relapsed CLL  \nVishaal Kunta , 1 Mohammad Ammad-Ud-Din ,2 Melanie Mediavilla-Varela , 1 and Javier Pinilla-Ibarz 1,2  \n1 Department of Immunology, H. Lee Moftt Cancer Center and Research Institute, 12902 USF Magnolia Drive,  \nTampa 33612, Florida, USA  \n2 Department of Malignant Hematology, H. Lee Moftt Cancer Center and Research Institute, 12902 USF Magnolia Drive, Tampa 33612, Florida, USA  \nCorrespondence should be addressed to Vishaal Kunta; [kuntav6971@acom.edu](kuntav6971@acom.edu)  \nReceived 12 May 2025; Revised 5 December 2025; Accepted 18 December 2025  \nAcademic Editor: Yoshito Nishimura  \nCopyright © 2026 Vishaal Kunta et al. Case Reports in Hematology published by John Wiley & Sons Ltd. Tis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.  \nBackground: Central nervous system (CNS) involvement is an infrequent complication of chronic lymphocytic leukemia (CLL), occurring in less than 1% of cases. We report a case of a 63-year-old male with a history of CLL previously treated with ibrutinib but discontinued early due to intolerance. As a result, the patient was then treated with obinutuzumab plus venetoclax, achieving undetectable minimal residual disease (MRD) but relapsed after 2 years with CNS involvement.  \nCase Presentation: Te patient initially presented to the emergency department with confusion and altered mental status. Magnetic resonance imaging (MRI) of the brain revealed abnormal subcortical hyperintensities and leptomeningeal enhancement concerning leukemic infltration. Lumbar puncture confrmed malignant CD5+ CLL cells in the cerebrospinal fuid (CSF), anda bone marrow biopsy revealed 50%–60% CLL involvement. Zanubrutinib 320 mg daily was initiated. Te patient exhibited marked cognitive improvement within full resolution after four weeks of therapy. Follow-up MRI after 8 weeks showed full resolution of CNS, lesions with repeat LP demonstrating CSF cleared of CLL cells. He remains in complete remission with continued daily zanubrutinib 6 months follow-up; no signifcant adverse efects were observed.  \nConclusion: Tis case highlights the rare occurrence of CNS involvement in CLL and is the frst to demonstrate successful CNS disease eradication with zanubrutinib monotherapy.  \n1. Introduction  \nChronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western countries, typically afecting older adults (median age around 70 years) [1, 2] . It is characterized by clonal accumulation of mature CD5+ Blymphocytes in the peripheral blood, bone marrow, and lymphoid tissues [1] . Te disease course is usually indolent, with many patients managed initially by observation. Standard frst-line treatments, when indicated by symptomatic disease or cytopenias, have evolved from chemoimmunotherapy (e.g., fudarabine, cyclophosphamide, andrituximab) to targeted agents, including BTK inhibitors  \n(ibrutinib, acalabrutinib, and zanubrutinib) and the BCL2 inhibitor venetoclax (often combined with anti-CD20 antibodies) [1, 3] . Tese novel agents have signifcantly improved CLL outcomes.  \nDespite improved sensitivity of CLL diagnosis, CLL rarely involves extranodal sanctuary sites. In particular, CNS involvement by CLL is an infrequent event [2] . While historical autopsy studies indicated occult CNS infltration in up to 70% ofCLL cases, clinically symptomatic “leukemic meningitis” or brain parenchymal infltration is reported in less than 1% of patients [1, 2] . Tere are no well-defned risk factors for this condition since CNS involvement can occur at any time in the disease course (median around 2.6 years  \n2 Case Reports in Hematology  \n(a) ","cbCaivvtrbyBx5Bp","https://ap.wps.com/l/cbCaivvtrbyBx5Bp","pdf",706402,"English","# Case Report\n## Background\n## Case Presentation\n## Conclusion\n# Introduction\n## CLL overview and treatment landscape\n## CNS involvement in CLL\n## Rationale for zanubrutinib","[{\"question\":\"How rare is CNS involvement in chronic lymphocytic leukemia (CLL)?\",\"answer\":\"CNS involvement occurs in less than 1% of CLL cases. It is described as an infrequent complication.\"},{\"question\":\"What were the key findings when the patient first presented?\",\"answer\":\"The patient had confusion and altered mental status. Brain MRI showed abnormal findings concerning leukemic infiltration, and lumbar puncture confirmed malignant CD5+ CLL cells in CSF.\"},{\"question\":\"What outcome did zanubrutinib monotherapy achieve?\",\"answer\":\"After starting zanubrutinib 320 mg daily, the patient showed marked cognitive improvement within four weeks, followed by full resolution of CNS lesions by follow-up MRI and repeat lumbar puncture demonstrating CSF clearance of CLL cells. He remained in complete remission at six months with no significant adverse effects reported.\"}]","Successful Zanubrutinib Monotherapy in a Rare CNS Presentation of Relapsed CLL - Case Report | PDF",1790707242,13]