title: Present and future treatment options for primary CNS lymphoma.
abstract: BACKGROUND
  Primary Central Nervous System (CNS) lymphomas are a rare group of malignancies with peculiar clinical and biologic features, aggressive course, and unsatisfactory outcome in contrast with other aggressive lymphomas. Despite a high chemo- and radiosensitivity, remissions are frequently short lasting, mainly because the blood-brain barrier limits the access of many drugs to the CNS, preventing a homogeneous treatment of all CNS tissues. Moreover, survivor patients are at high risk of developing severe treatment-related toxicity, mainly disabling neurotoxicity for elderly ones, raising the question of whether to intensify therapy to improve the cure rate or to downgrade treatment to reduce side effects. Although prognosis remains poor, it has significantly improved over the past two decades as a result of better treatment strategies with a curative aim.
  
  
  METHODS
  The purpose of this review is to focus on either the actual pharmaco-therapeutic knowledge or the predictable future developments for the immunocompetent population (the vast majority of patients today). The most important published reports on these fields are presented.
  
  
  CONCLUSIONS
  Actual front-line therapy consists of high-dose-methotrexate-based polichemotherapy, mostly in combination with high-dose cytarabine and/or alkylating agents. The use of high-dose chemotherapy supported by autologous stem-cell transplantation is increased; with some pros and cons, this strategy appears in controlling microscopic disease. Management of intraocular and meningeal lymphomas is controversial considering their peculiar characteristics that need to be specifically addressed. Finally, management of elderly patients and of relapsed disease is addressed.
authors.affiliation: a 1 IRCCS San Raffaele Scientific Institute, Unit of Lymphoid Malignancies, Division of Onco-Hematological Medicine, Department of Onco-Hematology , Milano, Italy +39 02 26 43 76 49 ; +39 02 26 43 24 08 ; ferreri.andres@hsr.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Citterio
authors.affiliation: b 2 IRCCS San Raffaele Scientific Institute, Department of Oncology , Milano, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Reni
authors.affiliation: a 1 IRCCS San Raffaele Scientific Institute, Unit of Lymphoid Malignancies, Division of Onco-Hematological Medicine, Department of Onco-Hematology , Milano, Italy +39 02 26 43 76 49 ; +39 02 26 43 24 08 ; ferreri.andres@hsr.it.
authors.forename: Andrés José Maria
authors.initials: AJ
authors.lastname: Ferreri
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000532:radiotherapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008223:Lymphoma / Q000175:diagnosis / Q000188:drug therapy* / Q000532:radiotherapy; D011379:Prognosis; D016879:Salvage Therapy
keywords: antimetabolites; autologous stem cell transplantation; chemotherapy; high-dose chemotherapy; intraocular lymphoma; primary central nervous system lymphoma; rituximab