Efficacy and Tolerability of Liposomial Cytosine Arabinoside (DepoCyte®) for the Treatment of Lymphomatous and Leukemic Meningitis.

Meningeal blastic involvement is a severe complication of aggressive non-Hodgkin lymphoma (NHL) and acute leukemia (AL). DepoCyte® is an unique liposomal formulation for IT administration, that provides a lower toxicity profile and a more convenient dosing regimen compared with other treatments, such as radiotherapy, high-dose (HD) or intrathecal (IT) chemotherapy (CT). Twentyseven patients (pts) with meningeal involvment from aggressive NHL or AL treated with DepoCyte® at the standard dose of 50 mg every 2 weeks were evaluated for cytological negativization of the cerebro-spinal fluid (CSF) from neoplastic cells and improvement of neurologic symptoms. Seventeen had a diagnosis of aggressive NHL and 10 of AL; only 1 pt affected by DLBCL was HIV positive. Median age was 50,3 years. (range 23–81). Five pts showed meningites at the diagnosis associated with systemic disease, 3 pts had isolated meningeal recurrence and the remaining systemic recurrence associated with meningeal involvement; these data are not available for PCNSL pts. All patients received standard therapies for their systemic disease, except 3 elderly DLBCL pts not receiving any systemic treatment; 9 pts received CNS prophylaxis. Four pts had received previous HD- or IT CT for meningeal localization. A total of 93.cycles were administred (median cycles/pt: 3,6; range 1–8). Overall responses (OR) of both NHL and AL pts are 16/27. Four pts with DLBCL recorded a complete response (RC) or a partial response (PR), both neurological and cytological, 3 had a progressive disease (PD) and 1 pt was not evaluable because he is still in treatment and has received only 1 administration of DepoCyte®. Two Burkitt-like lymphoma pts recorded a neurological and cytological CR, but 1 HIV+ pt showed a PD. One Burkitt’s lymphoma showed a PR; 1 mantle cell lymphoma had a CR, while a second mantle cell lymphoma pt recorded a cytological PR and no neurological improvement. Among ALL pts, 5 had a neurological and cytological CR, whereas 1 recorded a PD. All 3 AML pts had a response (1 PR and 2 CR). PTS with PCNSL, lymphoblastic lymphoma and CML in blastic phase pts had a neurological and cytological PD. No dose reduction was required for toxicity. In 1 DLBCL pt receiving concomitant hyperCVAD, G4 neutropenia was recorded, together with G2 anemia and G1 PLTpenia,. A mantle cell lymphoma pt showed G3 neutropenia and mental confusion. Depocyte® appears to be a feasible and active therapeutic option for lymphomatous and leukemic meningitis. Tolerability has been confirmed largely in previous studies. Randomized phase II trials are needed to settle up the efficacy in meningitis of lymphoblastic and myeloid leukemias.