Should intra-cerebrospinal fluid prophylaxis be part of initial therapy for patients with non-Hodgkin lymphoma: what we know, and how we can find out more.

Central nervous system (CNS) involvement is a serious complication of non-Hodgkin lymphoma (NHL), with an extremely poor outcome. In most cases, relapse in the CNS manifests as leptomeningeal disease. The relatively short interval between the initial diagnosis of NHL and CNS involvement implies that seeding of the cerebrospinal fluid occurs early in the natural history of the disease and suggests a role for CNS prophylaxis during initial treatment. However, CNS prophylaxis in patients with aggressive NHL remains controversial because of the relatively low incidence of CNS recurrence (5%-7%) in these patients and lack of consensus on the best therapies and protocols. Risk factors for CNS relapse in patients with aggressive NHL have been identified and may help define a subpopulation of patients for whom CNS prophylaxis is justified. Because of variation in current practice and a paucity of high-quality evidence, well-designed and controlled trials are needed to assess the benefits of prophylactic treatment in such a population. This article reviews the current role of CNS prophylaxis in patients with NHL and discusses issues in the conception, design, and execution of a clinical trial to elucidate the role of CNS prophylaxis in patients with aggressive NHL.