Abstract
Diffuse large B-cell lymphoma is the most common subtype of non-Hodgkin lymphoma. Central nervous system relapse is an uncommon but devastating complication, associated with poor prognosis and limited therapeutic options. Over the years, multiple strategies have been investigated to reduce the risk of central nervous system recurrence, although their efficacy remains controversial. This review aims to describe the evolution of central nervous system prophylaxis strategies in diffuse large B-cell lymphoma, highlighting risk stratification models, clinical outcomes, and emerging approaches designed to prevent central nervous system involvement.