How I treat secondary CNS involvement by aggressive lymphomas.

Secondary central nervous system lymphoma (SCNSL) is a rare but clinically challenging scenario with historically disappointing outcomes. SCNSL refers to lymphoma that has spread into the CNS concurrently with systemic disease, or CNS relapse during or after frontline immunochemotherapy, presenting with or without systemic lymphoma. Diffuse large B-cell lymphoma (DLBCL) denotes the most common entity but an increased incidence is observed in other histologies such as Burkitt lymphoma and mantle cell lymphoma. The incidence, timing in disease course, location, evidence supporting the use of CNS prophylaxis, and treatment pathways varies by histology. No randomized data exist to delineate the best treatment approaches with current recommendations based on retrospective and single-arm studies. However, a regimen comprised of immunochemotherapy, incorporating agents that cross the blood-brain barrier, followed by thiotepa-containing conditioning and autologous stem-cell transplant outlined in the international MARIETTA study demonstrated improvement in outcomes representing a major accomplishment in the care of DLBCL patients with SCNSL. Anti-CD19 chimeric antigen receptor T-cell denotes a paradigm shift in the treatment of patients with systemic aggressive lymphomas with emerging data also demonstrating efficacy without higher neurotoxicity in those with SCNSL. In this manuscript we discuss five clinical scenarios and review the evidence supporting our recommendations.