title: Incidence and risk factors for central nervous system occurrence in elderly patients with diffuse large-B-cell lymphoma: influence of rituximab.
abstract: BACKGROUND
  The incidence of secondary central nervous system (CNS) occurrences in diffuse large-B-cell lymphoma is not sufficiently high to warrant the use of CNS prophylaxis in all patients. The addition of rituximab increases the complete response rate and prolongs event-free and overall survival in elderly patients with such lymphoma.
  
  
  METHODS
  We analyzed a cohort of 399 elderly patients with lymphoma prospectively treated with eight cycles of CHOP with or without rituximab in order to assess if rituximab decreases the risk of CNS localization. Prophylaxis of CNS disease was not part of the treatment protocol.
  
  
  RESULTS
  We observed 20 CNS occurrences: 12 on therapy, four after partial remission and four following complete remission. In three patients, the CNS was the only site of relapse. In a multivariate analysis, increased age-adjusted International Prognostic Index (IPI) was the only independent predictive factor of CNS recurrence. Only three of 20 patients are alive with a follow-up of 24 months.
  
  
  CONCLUSIONS
  Rituximab did not influence the risk of CNS occurrence, possibly because of low rituximab diffusion. Direct intrathecal administration of rituximab could overcome this problem. We also confirmed that CNS occurrence is related to IPI as well as very poor prognosis of relapses occurring on therapy.
authors.affiliation: Service Hématologie, Service Informatique Médicale, Hôpitaux de Brabois, Nancy, France. p.feugier@chu-nancy.fr
authors.forename: P
authors.initials: P
authors.lastname: Feugier
authors.forename: J M
authors.initials: JM
authors.lastname: Virion
authors.forename: H
authors.initials: H
authors.lastname: Tilly
authors.forename: C
authors.initials: C
authors.lastname: Haioun
authors.forename: G
authors.initials: G
authors.lastname: Marit
authors.forename: M
authors.initials: M
authors.lastname: Macro
authors.forename: D
authors.initials: D
authors.lastname: Bordessoule
authors.forename: C
authors.initials: C
authors.lastname: Recher
authors.forename: M
authors.initials: M
authors.lastname: Blanc
authors.forename: T
authors.initials: T
authors.lastname: Molina
authors.forename: P
authors.initials: P
authors.lastname: Lederlin
authors.forename: B
authors.initials: B
authors.lastname: Coiffier
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000556:secondary*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015994:Incidence; D007278:Injections, Spinal; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D000069283:Rituximab; D016019:Survival Analysis; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone