Central Nervous System Relapse of Aggressive B-cell Lymphoma: Insights Into Current Treatment Approaches

Abstract

Central nervous system (CNS) relapse of lymphoma, also known as relapse with secondary CNS lymphoma (SCNSL), is a rare but devastating complication that confers poor survival outcomes and treatment decision challenges. Diffuse large B-cell lymphoma (DLBCL) accounts for most cases with an incidence of 4-6% and commonly occurs within 1 year of diagnosis (median of 5 months). However, CNS relapse is also seen in the context of other aggressive B-cell lymphoma histological subtypes, such as Burkitt lymphoma and mantle cell lymphoma, with an incidence of 20% and 4%, respectively. Identifying patients at risk of CNS relapse has been limited by the low sensitivity of diagnostic variables and scores. More recently, the use of CNS prophylaxis with high-dose methotrexate (HD-MTX) in DLBCL has also been challenged. CNS involvement can be parenchymal (40-50%), leptomeningeal (30-40%), or both (10-15%). Clinical presentation can occur with a range of neurological symptoms depending on the location of CNS involvement (e.g. motor deficits, symptoms related to increased intracranial pressure, cognitive/personality changes, visual disturbance) together with possible systemic symptoms in the presence of concurrent systemic disease involvement. For ease of making treatment decisions and understanding various approaches to management, SCNSL can be divided into 3 distinct clinical scenarios: 1) treatment-naïve-SCNSL, in which CNS involvement of lymphoma occurs concurrently with systemic disease at diagnosis; 2) relapsed isolated-SCNSL, in which relapse of previously treated systemic disease occurs isolated to the CNS; and 3) relapsed concurrent-SCNSL, in which relapse of previously treated systemic disease occurs both within the CNS and systemically.

This review will focus on treatment approaches for SCNSL in the relapsed setting, both relapsed isolated-SCNSL and relapsed concurrent-SCNSL, confined to DLBCL.