Current management of central nervous system involvement in chronic lymphocytic leukemia/small lymphocytic lymphoma

Central nervous system (CNS) involvement in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is an uncommon but increasingly recognized clinical entity. It has a highly heterogeneous presentation, ranging from subtle cognitive dysfunction to severe neurological deficits, and may occur at diagnosis or relapse. The diagnosis requires a high index of suspicion, integrating clinical, radiologic, and cerebrospinal fluid findings while excluding "bystander" contamination by circulating CLL cells.Management remains non-standardized and largely extrapolated from small case series and experience with other hematologic malignancies. Systemic therapy using medications with reliable CNS penetration is the cornerstone of treatment. Bruton tyrosine kinase inhibitors and venetoclax-based regimens demonstrate favorable pharmacokinetics and clinical outcomes. Intrathecal chemotherapy remains an important adjunct to systemic therapy, while radiotherapy is reserved for rapid symptom control or palliative purposes.For relapsed or refractory CLL with CNS involvement, therapeutic decisions should consider prior treatment history and resistance mechanisms. Emerging modalities such as CAR-T cell therapy and allogeneic hematopoietic stem cell transplantation may offer durable remission in select patients.CNS involvement in CLL remains underdiagnosed and understudied. Further research is needed to define optimal treatment strategies and improve survival outcomes in the era of targeted therapy.