Case Report: Leptomeningeal involvement in chronic lymphocytic leukemia patients with central nervous system infection: extramedullary manifestation or transmigration of leukocytes—how to treat this type of CLL?

Central nervous system (CNS) involvement by CLL is rare. We report a non-treated CLL patient with low-risk factors, but showed leptomeningeal involvement during/after neuroborreliosis and EBV meningitis. An 80-year-old woman with CLL in Binet stage A showed neurological syndromes and increased leukocytosis. The initial cerebrospinal fluid (CSF) revealed EBV-meningitis and neuroborreliosis, but no evidences for CNS involvement of CLL by flow cytometry and morphological/immunochemical assays. After antimicrobial treatment, neurological syndrome were significant improved. However, leukemic meningeal involvement was proved in following CSF analyses. Treatment with intrathecal chemotherapy and Bruton’s tyrosine kinase inhibitor (BTKi) Zanubrutinib were performed. At the follow-up after 12 months, a complete remission was observed. Considering the case of our patient and previous reports, the question arises whether the detection of leukemic cells in the CSF of CLL patients with/after infectious meningitis (especially in neuroborreliosis) is an extramedullary manifestation or only a transmigration of clonal lymphocytes caused by the inflammation of the blood-brain barrier. The prophylaxis of CNS infections should be more seriously, since it may be associated with CLL leptomeningeal involvement. The need for an individualized therapy is certain, our case confirmed the efficacy of Zanubrutinib.