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

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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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