Central Nervous System Involvement is Associated with Ibrutinib-Induced Severe Hyperleukocytosis and Controlled by the Combination of Intrathecal Chemotherapy in Chronic Lymphocytic Leukemia: A Case Report

Central nervous system involvement (CNSi) is a rare complication of chronic lymphocytic leukemia (CLL) with a very poor prognosis. Its diagnosis, predictive factors, and standard treatment remain elusive. Ibrutinib, an oral inhibitor of Bruton’s tyrosine kinase, has been approved to treat CLL, yet little is known of its effect on the occurrence and management of CNSi. Here, we report, for the first time, an elderly CLL patient with secondary CNSi following ibrutinib-induced severe hyperleukocytosis, characterized by subcutaneous lesions and unmutated IgHV gene. Ibrutinib combined with intrathecal chemotherapy induced a prompt and durable remission of CNSi. This case indicates that severe hyperleukocytosis caused by ibrutinib is associated with the emergence of CNSi, and a combined treatment with intrathecal chemotherapy is effective and safe in the treatment of CLL patient with CNSi.