Central nervous system involvement in CLL: an international retrospective study by ERIC, the European Research Initiative on CLL

Central nervous system involvement (CNSi) of chronic lymphocytic leukemia (CLL) is a rare condition with no consensus on diagnostic criteria and limited evidence for management and outcome. Here, we report an international, multicenter, retrospective study conducted by the European Research Initiative on CLL. The study defined CNSi of CLL by the following: (1) detection of CLL cells in the cerebrospinal fluid or confirmation of CLL infiltration of the CNS based on a tissue biopsy, (2) clinical or radiographic evidence of neurologic disease, and (3) the absence of other explanations for the neurologic findings. A total of 48 patients from 26 centers in 15 countries met all 3 diagnostic criteria of CLL-CNSi. Median age at diagnosis of CNSi was 64 years. Most patients were males (73%), had Binet stage A at CLL diagnosis (61%), and had untreated CLL at the time of CNSi (63%). Motor impairment was the most common symptom (38%) followed by visual impairment (32%). Of 47 patients who received treatment for CNSi, half (51%) received targeted agents, most often a Bruton tyrosine kinase inhibitor (BTKi), and 34% received chemoimmunotherapy. Initial treatment was highly effective, leading to a reduction (83%) or complete resolution (71%) of neurologic symptoms and imaging findings in most patients. The estimated 5-year overall survival (OS) from the CNSi diagnosis was 77.1%. The 5-year time to next treatment or death was 94% for patients treated with BTKi compared with 64% for those treated with CIT. Treatment-sensitive disease, represented by attainment of CNS complete response after initial therapy, was associated with longer OS.

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Journal
Blood Advances
Published
2025-10-24
DOI
https://doi.org/10.1182/bloodadvances.2025017755
Primary Topic
Chronic Lymphocytic Leukemia Research
Type
article
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article

Central nervous system involvement in CLL: an international retrospective study by ERIC, the European Research Initiative on CLL

Miguel Arturo Pavlovsky, Odit Gutwein, Evangelia Minga, Enrica Antonia Martino et al.
Blood Advances
Chronic Lymphocytic Leukemia Research
article

Central nervous system involvement in CLL: an international retrospective study by ERIC, the European Research Initiative on CLL

Miguel Arturo Pavlovsky, Odit Gutwein, Evangelia Minga, Enrica Antonia Martino, Massimo Gentile, Ιoannis Kotsianidis, Jennifer R. Brown, María José Mela Osorio, Ewa Wąsik‐Szczepanek, Juan Marquet, Blanca Ferrer Lores, Alessandro Cellini, Riccardo Moia, Christian Brieghel, Eugene Nikitin, Lydia Scarfò, Celso Arrais‐Rodrigues, Anastasia Chatzidimitriou, Münci Yağcı, Maya Koren‐Michowitz, Pär Josefsson, Gianluca Gaïdano, Andrea Visentin, Michael Doubek, Κώστας Σταματόπουλος, Inhye E. Ahn, Blanca Espinet, Carsten Utoft Niemann, Maria Kislova, Thomas Chatzikonstantinou, Verena Pfister, Sotiria Dimou‐Besikli, Matthew Steven Davids, Enrico Lista, Emine Merve Savaş, Mariia Mikhaleva, Niki Stavroyianni, Amalia Cerutti, Paula Jabłonowska-Babij, Martin Šimkovič, Ozren Jakšić, Antigoni Tranidou, Elżbieta Kalicińska, Jose Antonio Garcia-Vela, Paolo Ghia, Lev Shvidel, Lisbeth Enggaard, Mary Ann Anderson, Tomasz Wróbel, Matjaž Sever, Yair Herishanu, Christina Papangelou, Eva Gimeno Vázquez, George Vrachiolias, Ciaran P McAuley, Claudia Mosquera Rubal, Persefoni Talimtzi
article en

Abstract

Central nervous system involvement (CNSi) of chronic lymphocytic leukemia (CLL) is a rare condition with no consensus on diagnostic criteria and limited evidence for management and outcome. Here, we report an international, multicenter, retrospective study conducted by the European Research Initiative on CLL. The study defined CNSi of CLL by the following: (1) detection of CLL cells in the cerebrospinal fluid or confirmation of CLL infiltration of the CNS based on a tissue biopsy, (2) clinical or radiographic evidence of neurologic disease, and (3) the absence of other explanations for the neurologic findings. A total of 48 patients from 26 centers in 15 countries met all 3 diagnostic criteria of CLL-CNSi. Median age at diagnosis of CNSi was 64 years. Most patients were males (73%), had Binet stage A at CLL diagnosis (61%), and had untreated CLL at the time of CNSi (63%). Motor impairment was the most common symptom (38%) followed by visual impairment (32%). Of 47 patients who received treatment for CNSi, half (51%) received targeted agents, most often a Bruton tyrosine kinase inhibitor (BTKi), and 34% received chemoimmunotherapy. Initial treatment was highly effective, leading to a reduction (83%) or complete resolution (71%) of neurologic symptoms and imaging findings in most patients. The estimated 5-year overall survival (OS) from the CNSi diagnosis was 77.1%. The 5-year time to next treatment or death was 94% for patients treated with BTKi compared with 64% for those treated with CIT. Treatment-sensitive disease, represented by attainment of CNS complete response after initial therapy, was associated with longer OS.

Blood AdvancesVol. 10(2)
Federal Institute of São Paulo (BR), Medical University of Lublin (PL), Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT), Hospital Británico (UY), Central European Institute of Technology (CZ), The Royal Melbourne Hospital (AU), University of Padua (IT), Democritus University of Thrace (GR), University of Ljubljana (SI), Vita-Salute San Raffaele University (IT), Tel Aviv University (IL), The University of Melbourne (AU), Walter and Eliza Hall Institute of Medical Research (AU), Charles University (CZ), Masaryk University (CZ), Instituto Cajal (ES), Universidad de Buenos Aires (AR), Tel Aviv Sourasky Medical Center (IL), Kaplan Medical Center (IL), Peter MacCallum Cancer Centre (AU), University Hospital Dubrava (HR), Ljubljana University Medical Centre (SI), Copenhagen University Hospital (DK), Rigshospitalet (DK), San Raffaele University of Rome (IT), Wroclaw Medical University (PL), Ospedale Santa Chiara (IT), Hospital Clínico Universitario de Valencia (ES), Azienda Ospedaliera di Cosenza (IT), Hospital Universitario Puerta de Hierro Majadahonda (ES), Centro Científico Tecnólogico - Rosario (AR), Provincia Autonoma di Trento (IT), Assaf Harofeh Medical Center (IL), Central European Institute of Technology (AT), Dana-Farber Cancer Institute (US), Botkin Hospital (RU), Hospital Del Mar (ES), Fundación para la Investigación, Docencia y Prevención del Cáncer (AR), Ospedale Annunziata di Cosenza (IT), Centre for Research and Technology Hellas (GR), University Hospital Hradec Králové (CZ), Instituto Cardiovascular de Rosario (AR), Danish Cancer Society (DK), G. Papanikolaou General Hospital (GR), University Hospital of Alexandroupolis (GR), Hospital Universitario Ramón y Cajal (ES), University of Calabria (IT), Universidade Federal de São Paulo (BR), Gazi University (TR)
Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, AstraZeneca, Leukemia and Lymphoma Society, Gilead Sciences, CSL Behring, TG Therapeutics, MEI Pharma, Associazione Italiana per la Ricerca sul Cancro, Grifols
Openalex Percentile: Top 58%
Chronic Lymphocytic Leukemia Research
DOIOpen Access PDFOpenAlex
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