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Multicenter Study
. 2026 Jan 27;10(2):428-438.
doi: 10.1182/bloodadvances.2025017755.

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

Thomas Chatzikonstantinou  1 , Mariia Mikhaleva  2 , Christian Brieghel  3   4 , Christina Papangelou  1 , Eva Minga  1 , Celso Arrais-Rodrigues  5 , Sotiria Besikli-Dimou  1 , Amalia Cerutti  6 , Michael Doubek  7   8 , Lisbeth Enggaard  3 , Blanca Espinet  9 , Blanca Ferrer-Lores  10 , Jose Antonio Garcia Vela  11 , Massimo Gentile  12   13 , Eva Gimeno Vázquez  14 , Odit Gutwein  15   16 , Yair Herishanu  17 , Paula Jablonowska-Babij  18 , Ozren Jaksic  19 , Par Josefsson  3 , Elzbieta Kalicińska  18 , Maria Kislova  20 , Enrico Lista  21 , Ioannis Kotsianidis  22 , Juan Marquet  23 , Enrica Antonia Martino  13 , Ciaran McAuley  24   25   26 , Maria José Mela Osorio  27 , Riccardo Moia  28 , Claudia Mosquera  12 , Eugene Nikitin  20 , Miguel Arturo Pavlovsky  27 , Verena Pfister  5 , Emine Merve Savaş  29 , Lydia Scarfò  30   31 , Matjaz Sever  32 , Lev Shvidel  33 , Martin Simkovic  34 , Niki Stavroyianni  35 , Persefoni Talimtzi  1 , Antigoni Tranidou  1 , Andrea Visentin  36 , Georgios Vrachiolias  22 , Ewa Wasik-Szczepanek  37 , Tomasz Wróbel  18 , Münci Yağcı  29 , Alessandro Cellini  36 , Anastasia Chatzidimitriou  1 , Gianluca Gaidano  28 , Mary Ann Anderson  24   38   39 , Matthew S Davids  2 , Jennifer R Brown  2 , Carsten U Niemann  3   4 , Kostas Stamatopoulos  1 , Paolo Ghia  30   31 , Inhye E Ahn  2 , Maya Koren-Michowitz  15   16
Affiliations
Multicenter Study

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

Thomas Chatzikonstantinou et al. Blood Adv. .

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.

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Conflict of interest statement

Conflict-of-interest disclosure: T.C. reports honoraria from AbbVie, AstraZeneca, and BeOne. Y.H. reports honoraria from AbbVie, Janssen, Roche, Medison, and Lilly; served on advisory boards for BeOne and Lilly; and reports research support from Janssen. L. Scarfò reports honoraria from AbbVie, AstraZeneca, BeOne, Johnson & Johnson, Lilly, and Merck. M. Simkovic reports honoraria from, served on advisory boards for, and reports travel support from AbbVie, AstraZeneca, Swixx Biopharma, Eli Lilly, and Johnson & Johnson. A.V. served on advisory boards for AbbVie, AstraZeneca, BeOne Medicines, CSL Behring, Johnson & Johnson, and Takeda; and speakers' bureaus for AbbVie, Johnson & Johnson, and Lilly. G.G. served on advisory boards and served on speakers' bureaus for AbbVie, AstraZeneca, BeOne, Hikma, Incyte, Johnson & Johnson, and Lilly. M.A.A. is an employee of the Walter and Eliza Hall Institute which receives milestone payments in relation to venetoclax to which M.A.A. is entitled to a share; and reports honoraria from AbbVie, AstraZeneca, Janssen, BeOne, Novartis, Roche, Takeda, CSL, and Gilead. J.R.B. has served as a consultant for AbbVie, Acerta/AstraZeneca, Alloplex Biotherapeutics, BeOne, Bristol Myers Squibb, EcoR1, Galapagos NV, Genentech/Roche, Grifols Worldwide Operations, InnoCare Pharma Inc, Loxo/Lilly, Magnet Biomedicine, Merck, and Pharmacyclics; reports research funding from BeOne, Gilead, iOnctura, Loxo/Lilly, MEI Pharma, Nagoon Therapeutics, and TG Therapeutics; and serves on the data safety monitoring board for Grifols Therapeutics. P.G. reports honoraria from AbbVie, AstraZeneca, BeOne, Bristol Myers Squibb, Galapagos, Genmab, Johnson & Johnson, Lilly/LoxoOncology, Merck Sharp & Dohme, and Roche; and research funding from AbbVie, AstraZeneca, Bristol Myers Squibb, Johnson & Johnson, Lilly/LoxoOncology, and Merck Sharp & Dohme. K.S. reports research support from AbbVie, AstraZeneca, Janssen, Novartis, and Roche; honoraria from AbbVie, AstraZeneca, Bristol Myers Squibb, Lilly, and Janssen. I.E.A. reports institutional research funding from BeOne and Lilly; served as a consultant or advisory board for AstraZeneca, BeOne, and Lilly; and reports honoraria from Lilly. M.K.M. reports honoraria from Novartis, Bristol Myers Squibb, and Pfizer. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
CONSORT diagram.
Figure 2.
Figure 2.
OS of patients with CNSi. (A) OS from the first diagnosis of CNSi of CLL. (B) OS from the first CNS-directed treatment in patient subgroups divided by CR status after the treatment.
Figure 3.
Figure 3.
TTNT-D and OS of patients treated with BTKi compared to other therapies. (A) TTNT-D from the first CNS-directed treatment of patients who received BTKi-based regimens vs those who received CIT, including CNS lymphoma treatment regimens. (B) OS from the first CNS-directed treatment of patients who received BTKi-based therapy vs those who received CIT.
Figure 4.
Figure 4.
Univariable and multivariable analyses of risk factors associated with OS after the diagnosis of CLL with CNSi.
See this image and copyright information in PMC

References

    1. Strati P, Uhm JH, Kaufmann TJ, et al. Prevalence and characteristics of central nervous system involvement by chronic lymphocytic leukemia. Haematologica. 2016;101(4):458–465. - PMC - PubMed
    1. Hanse MC, Van't Veer MB, van Lom K, van den Bent MJ. Incidence of central nervous system involvement in chronic lymphocytic leukemia and outcome to treatment. J Neurol. 2008;255(6):828–830. - PubMed
    1. Jellinger K, Radiaszkiewicz T. Involvement of the central nervous system in malignant lymphomas. Virchows Arch A Pathol Anat Histol. 1976;370(4):345–362. - PubMed
    1. Bojsen-Møller M, Nielsen JL. CNS involvement in leukaemia. An autopsy study of 100 consecutive patients. Acta Pathol Microbiol Immunol Scand A. 1983;91(4):209–216. - PubMed
    1. Witton LA, Menon S, Perera KS. Central nervous system involvement with chronic lymphocytic leukemia. Can J Neurol Sci. 2019;46(5):640–641. - PubMed

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