Liposomal Cytarabine (DepoCyte®) for the Prophylaxis and Treatment of Central Nervous System Involvement In Adult Acute Lymphoblastic Leukemia (ALL) - A Retrospective Analysis

Central nervous system involvement in Acute Lymphoblastic Leukemia can be either primary, present at diagnosis or associated with relapse of the disease. Prevention and treatment of CNS relapse is an essential component of all ALL chemotherapy regimens. Liposomal cytarabine (DepoCyte) is a sustained release formulation of Ara-C with a homogeneous distribution throughout the neuroaxis and a prolonged half-life maintaining cytotoxic concentrations in the CSF for more than 14 days. DepoCyte obtained superior response rates, improved patient quality of life and improved the time to neurological progression compared to standard cytarabine in a randomized clinical trial (Glantz et al 1999).

A retrospective analysis was carried out to evaluate feasibility, safety and efficacy of DepoCyte in the prophylaxis and treatment of ALL patients. 45 patients who received 50mg liposomal cytarabine either as a prophylaxis (N=24) or treatment (N=21) between March 2006 – December 2009 in 4 centers in Poland were included in the analysis.

Baseline characteristics of patients who completed CNS prophylaxis with DepoCyte: median age 34 (range: 18–67 years), male/female ratio 16/8, B-cell ALL (n=17), T-cell ALL (n=4), Ph-positive ALL (n=3). In the treatment group median age was 35 (range 18–60), male/female ratio 12/9, B-cell ALL (n=15), T-cell ALL (n=3) and Ph-positive ALL (n=3).

In the prophylaxis group the average number of DepoCyte administrations was 2.6 (range 2–4). Oral or IV Dexamethasone for 5 days was given to all patients to prevent symptoms of arachnoiditis. With a median follow-up of 12 months (range: 3–27) only 1 pt developed combined systemic and CNS relapse. 25% of patients (6/24) experienced mild and transitory adverse events: headache (n=3), brain edema during methotrexate-containing consolidation (n=1) and post-puncture syndrome (n=2).

In the treatment group 8 pts were in first isolated CNS relapse and 13 pts were in combined CNS and systemic relapse. All patients had neurological symptoms and blast cells identified in the cerebrospinal fluid with average cellularity 713/μL (range 20–2500/μL). In 2 patients CNS disease was confirmed by computed tomography. DepoCyte was administered intrathecally together with systemic chemotherapy in 18 patients. The treatment was planned to avoid concomitant administration of DepoCyte and other cytotoxic agents that cross the BBB. All patients received concurrent dexamethasone for prophylaxis of arachnoiditis. Neurological and cytological responses were obtained in all 21 pts (16 CRs and 5 PRs). No serious adverse events with DepoCyte were reported. Mild headache was the most commonly reported toxicity (10/21pts, 47.6%). 2 out of 21 (9.5%) heavily pretreated patients developed transient sacral radiculopathy.

1) Implementation of liposomal cytarabine as IT prophylaxis in ALL patients reduces the total number of IT injections, is feasible and effective and has a favorable tolerance profile. 2) DepoCyte used for the treatment of leukaemic meningitis with concurrent systemic chemotherapy is a highly effective and feasible treatment in isolated and combined CNS relapse in ALL. 3) DepoCyte is generally well tolerated when concurrent dexamethasone is administered to alleviate symptoms of arachnoiditis and concomitant administration of agents that cross the BBB is avoided.

Glantz M et al. Randomized trial of a slow release versus a standard formulation of cytarabine for the intrathecal treatment of lymphomatous meningitis. J Clin Oncol 1999; 17: 3110-17.

No relevant conflicts of interest to declare.