Management of Immunocompetent Patients With Primary Central Nervous System Lymphoma

Abstract

Primary central nervous system (CNS) lymphoma (PCNSL) is a non-Hodgkin lymphoma that arises within and is confined to the CNS. Recent data have suggested an increasing incidence in immunocompetent individuals, with a peak of incidence between 60 and 70 years of age. Patients with PCNSL present mostly with symptoms of increased intracranial pressure. The clinical management of these patients remains controversial, and the optimal treatment for patients with PCNSL has not yet been defined. Surgery, even if macroscopically radical, does not improve survival because of the multifocal and infiltrative nature of PCNSL; furthermore, the deep location of most of these tumors makes patients susceptible to serious and irreversible neurologic sequelae. Corticosteroids have a specific role in the treatment of patients with PCNSL, whose disease is sensitive to them as a chemotherapeutic agent. PCNSL is an extremely radiation-sensitive neoplasm; whole-brain radiation therapy plus corticosteroids was the first modality of treatment for patients with this neoplasm until 10 years ago, with a low cure rate and a high local recurrence rate. PCNSL is also a chemosensitive neoplasm; while the optimal choice, sequence, and combination of appropriate agents for efficacious treatment of patients with PCNSL has yet to be determined. An essential component of therapy must include an adequate drug delivery behind a normal blood-brain barrier. Methotrexate is the agent with the most proven activity in PCNSL. Combined-modality therapy has improved survival, but relapse is still common, and late neurologic toxicity is a significant complication, especially in older patients, who represent the majority of immunocompetent patients with PCNSL.