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A Mayo Clinic retrospective study identified 36 patients with biopsy-confirmed RT to DLBCL or high-grade B-cell lymphoma and documented CNS involvement from 01/2005 to 08/2024. Outcomes used Kaplan–Meier overall survival from CNS involvement, incorporating clinical, pathological, molecular, and treatment data. Median overall survival was 13.0 months, with longer survival in isolated CNS disease and in treatment-naïve CLL patients.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/central-nervous-system-involvement-in-patients-with-richter-transformation-of-chronic-lymphocytic-leukemia-cll-the-mayo-clinic-experience-correspondence-open/456769/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/central-nervous-system-involvement-in-patients-with-richter-transformation-of-chronic-lymphocytic-leukemia-cll-the-mayo-clinic-experience-correspondence-open/456769.png","ImageObject",300,407,{"name":42,"@type":43},"Emma Wilson","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-05","2026-09-30",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",10,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What is Richter transformation involving the central nervous system (RT-CNS)?","Question",{"text":63,"@type":64},"RT-CNS refers to chronic lymphocytic leukemia transforming into an aggressive lymphoma with CNS involvement. The document notes this scenario is rare and largely supported by case reports and small series.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How were patients selected for the Mayo Clinic retrospective study?",{"text":68,"@type":64},"Patients with biopsy-confirmed RT to DLBCL or high-grade B-cell lymphoma diagnosed between 01/2005 and 08/2024 were included if CNS involvement by aggressive lymphoma was documented by biopsy or imaging.",{"name":70,"@type":61,"acceptedAnswer":71},"What were the main overall survival findings after CNS involvement?",{"text":72,"@type":64},"After a median follow-up of 62.7 months, median overall survival following CNS involvement was 13.0 months. Isolated CNS involvement showed longer median OS than concurrent systemic and CNS disease, and CLL treatment-naïve patients had longer OS than those previously treated.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},456769,1790888800,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":55,"slug":125},"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":97,"language":139,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":12,"update_tm":143,"read_time":144,"preview_page_count":4},3848291630094,"https://eur-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","Blood Cancer [Journal](Journal www.nature.com/bcj)[ www.nature.com/bcj](Journal www.nature.com/bcj)  \nCORRESPONDENCE OPEN   \nCentral nervous system involvement in patients with Richter transformation of chronic lymphocytic leukemia (CLL): the Mayo Clinic experience  \n© The Author(s) 2026  \nBlood Cancer Journal (2026)16:7; [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.1038/s41408-025-01446-y](10.1038/s41408-025-01446-y)  \nTo the Editor:  \nRichter transformation (RT) is the transformation of chronic lymphocytic leukemia (CLL) into an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL) . RT involving the central nervous system (RT-CNS) is rare with existing knowledge largely limited to case reports and small series, leaving major gapsin understanding its clinicopathologic features, prognostic markers, and optimal management [1–5] . In the absence of established guidelines, most clinicians rely on treatment strategies extrapolated from primary CNS lymphoma (PCNSL) and secondary CNS DLBCL (SCNS-DLBCL) [6–9] . Given the limited data in this setting, we conducted a retrospective study to describe the clinical features, molecular proﬁle, treatment strategies, survival outcomes and prognostic factors for patients with RT-CNS.  \nThis study was approved by the Mayo Clinic Institutional Review Board. Patients with biopsy-conﬁrmed RT to DLBCL or high-grade Bcell lymphoma (HGBCL) diagnosed between 01/2005 and 08/2024 and documented CNS involvement by aggressive lymphoma (biopsy-or imaging-conﬁrmed) were identiﬁed. Clinical, pathological, molecular, and treatment data were abstracted. Overall survival (OS) was deﬁned as time from CNS involvement to death from any cause and analyzed with the Kaplan–Meier method. Statistical analyses were performed using SPSS v28.0 and BlueSky v10.3.4 .  \nThirty-six patients with RT-CNS were identiﬁed. Baseline characteristics are summarized in Table 1. The median age at CLL diagnosis was 63 years (range 34–78) and 58.3% were male. High-risk disease features at CLL phase included TP53 alteration (mutation and/or del(17p)) in 12 of 25 (48.0%) and unmutated IGHV in 8 of 15 (53.3%) . Of the 36 patients, 24 (67.0%) were treatment-naïve for CLL at the time of RT diagnosis. The median time from CLL to RT diagnosis in these patients was 3.1 months (range 0–124.5) . Among the 12 patients (33.0%) previously treated for CLL, the median number of CLL treatment lines prior to RT was 1.5 (range 1–5) and the median time from CLL to RT diagnosis was 75.9 months (range 0.3–277.4) .  \nThe median age at RT diagnosis was 69 years (range 46–79) . RT histology was DLBCL in 33 patients and HGBCL in 3 (including two MYC/BCL2 double-hit and one HGBCL-NOS) . Elevated LDH was noted in 33 patients (91.7%) . Median Ki-67 was 90% (range 25–100%; n = 16) . Clonal relatedness between CLL and RT based on B-cell gene (i.e., IGHV) rearrangement (BCGR) was related in 12 (75 .0%) and unrelated in 4 (25 .0%) .  \nThe median age at CNS involvement was 69 years (range 46–80) . CNS involvement was parenchymal in 12 (33.3%), nonparenchymal in 13 (36.1%), and mixed in 11 (30.6%) . Nineteen  \n(52.8%) had isolated CNS disease, while 17 (47.2%) also had systemic involvement. CNS involvement occurred at RT diagnosis in 22 patients and at RT progression in 14 . Among the latter, the median interval from RT diagnosis to CNS involvement was 11.1 months (range 1–41.6) and median line of prior RT therapy was 1 (range 1–5) . Prior RT treatments included R-CHOP-based frontline only in 8 (22.9%), R-CHOP plus salvage in 5 (14.3%), and obinutuzumab plus high-dose methylprednisolone in 1 (2.9%)(Supplemental Table 1) .  \nTreatments for RT-CNS are summarized in Supplemental Tables 1, 2 . Among 19 patients with isolated CNS disease, 15 received high dose (HD) methotrexate (MTX)-based therapy (1 HD-MTX alone, 8 HD-MTX+ rituximab [MR], 5 HD-MTX + rituximab + temozolomide [MRT], 1 MATRix), 2 received other regimens (1 steroids only; 1 ri","cbCaidzDmhG9u23f","https://ap.wps.com/l/cbCaidzDmhG9u23f","pdf",966719,"English","# Correspondence open\n## Background and study rationale\n## Methods\n## Patient characteristics\n## CNS involvement patterns and treatments\n## Survival outcomes and prognostic signals","[{\"question\":\"What is Richter transformation involving the central nervous system (RT-CNS)?\",\"answer\":\"RT-CNS refers to chronic lymphocytic leukemia transforming into an aggressive lymphoma with CNS involvement. The document notes this scenario is rare and largely supported by case reports and small series.\"},{\"question\":\"How were patients selected for the Mayo Clinic retrospective study?\",\"answer\":\"Patients with biopsy-confirmed RT to DLBCL or high-grade B-cell lymphoma diagnosed between 01/2005 and 08/2024 were included if CNS involvement by aggressive lymphoma was documented by biopsy or imaging.\"},{\"question\":\"What were the main overall survival findings after CNS involvement?\",\"answer\":\"After a median follow-up of 62.7 months, median overall survival following CNS involvement was 13.0 months. Isolated CNS involvement showed longer median OS than concurrent systemic and CNS disease, and CLL treatment-naïve patients had longer OS than those previously treated.\"}]","Central nervous system involvement in patients with Richter transformation of chronic lymphocytic leukemia (CLL): the Mayo Clinic experience - Correspondence open | PDF",1790747040,13]