Phase II Study of Intrathecal Long Acting Liposomal Cytarabine (Depocyte^®) In the Prophylaxis of Lymphomatous Meningitis In HIV-Related Non-Hodgkin's Lymphoma

Around 5% of patients with aggressive non-Hodgkin's lymphoma (NHL) develop central nervous system (CNS) progression or relapse during the course of their disease. Patients with human immunodeficiency (HIV)-related NHL often develop CNS progression despite the use of adequate prophylaxis. Liposomal cytarabine has show a significant activity in lymphomatous meningitis but there are limited data in the prophylactic setting.

Since May 2006, we are running a prospective phase II study of intrathecal liposomal cytarabine (Depocyte®) at the dose of 50 mg in 40 patients with HIV-NHL with the aim to evaluate the feasibility and activity of this drug in the prevention of lymphomatous meningitis.

Thirty-five patients were males and the median age was 44 years (range 18–69 yrs). As far as the histological subtype of NHL, 47% of patients had a diffuse large B-cell (DLBC) NHL and 40% Burkitt NHL. Stage III-IV was diagnosed in 80% of patients and 68% of DLBC were age-adjusted IPI 2 or more. An extranodal involvement was diagnosed in 70% of patients (gastrointestinal 30%, bone 27%, spleen 10%, liver 22%, bone marrow 17%). Liposomal cytarabine was well tolerated with headache grade I to III being the most frequent side effect in only 37% of patients. Less common toxicity (all grade I) included cortical changes (5%), fever (3%), vomiting (3%), hypertension (3%), chills (3%). With a median follow up of 12.4 months only one patient (3%) with Burkitt lymphoma developed a combined systemic and meningeal relapse. Moreover, in our experience previously the present study, we used methotrexate as practical use in 426 HIV-NHL with a meningeal progression or relapse of 14% (p=0.09). The use of a liposomal formulation allowed to significantly reduce the number of lumbar injections in comparison to the standard schedules (approximately of 50%) with an improvement of quality of life of patients and with a reduction of professional exposure risk for health care staff.

In this first prospective study on prophylaxis of lymphomatous meningitis in HIV-NHL reported in the literature, liposomal cytarabine seems safe and active and it reduces of approximately 50% the number of lumbar punctures and exposure risk for health staff as well.

No relevant conflicts of interest to declare.