Incidence and Risk Factors for Central Nervous System Manifestation in Elderly Patients with Aggressive Non-Hodgkin's Lymphoma.

Abstract

Introduction: Manifestation of central nervous system (CNS) disease in patients with aggressive non-Hodgkin's lymphoma (NHL) during or after first line treatment is often a devastating condition, which is associated with a poor prognosis. There is today no general consensus regarding prophylactic treatment in this patient category, particularly in the elderly. The aim of this study was to define the incidence and risk factors for CNS manifestation in a large cohort of elderly (>60 years) patients with aggressive NHL and no CNS disease at diagnosis.Patients and methods: This Nordic study included a total of 455 previously untreated patients with advanced (stage II–IV) aggressive NHL without CNS involvement at diagnosis (Blood 2003; 101:3840). The vast majority had diffuse large B cell lymphoma. Patients (median age, 71 years; range, 60–86 years) were randomised to receive CHOP (doxorubicin 50 mg/m2) or CNOP (mitoxantrone 10 mg/m2) with or without G-CSF (5 microg/kg from day 2 until day 10–14 of each cycle every 3 weeks; 8 cycles). Intrathecal methotrexate was given as prophylaxis to patients with lymphoma bone marrow involvement and in patients with testicular, orbital, sinus and epidural sites of presentation.Results: At this time point information is available for 441/455 patients. After a median observation time of 113 months in surviving patients 30/441 (6.8%) developed CNS disease. Advanced stage (p=0.004) and a high age-adjusted International Prognostic Index (IPI; p=0.034) were associated with an increased risk of CNS disease. Age, sex, performance status, bone marrow involvement/extranodal disease, serum lactate dehydrogenase level, or treatment received were not related to the risk of CNS manifestation. All patients with CNS disease were dead at follow-up.Conclusion: A significant proportion of elderly patients with advanced aggressive NHL and no CNS manifestation at diagnosis develop CNS disease despite prophylactic measures in clinically defined high-risk patients. CNS occurrence is related to clinical stage and age-adjusted IPI. The prognosis of elderly aggressive NHL patients with CNS manifestation is poor.