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Secondary central nervous system (CNS) lymphoma (SCNSL) can occur at the time of systemic lymphoma diagnosis or in relapse, either isolated or with systemic disease. Therapeutically, controlling both systemic and CNS disease is a challenge, requiring agents that penetrate the blood-brain barrier. Intensive chemotherapy regimens, including high-dose methotrexate and hematopoietic stem cell transplantation, have shown favorable outcomes. However, effective treatment strategies are still needed, and the incorporation of novel agents in immunochemotherapy requires further study in prospective trials.

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