Compassionate Use of Intrathecal Depot Cytarabine (DepoCyte®) in Central Nervous System (CNS) Involvement in Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma in Spain: Report of 10 Cases.

The efficacy of intrathecal (IT) depot formulation of liposomal cytarabine (DepoCyte^®) in the treatment of CNS involvement in patients with ALL has been only demonstrated in individual cases or series with a small number of patients. A retrospective review was performed of all cases in which IT depot cytarabine was employed as compassionate therapy of CNS involvement of ALL and lymphoblastic lymphoma in Spain. From February 2004 to March 2006, 10 cases (6 females) were recorded (ALL, 6, lymphoid blast crisis [BC] of Ph’ CML, 2, and lymphoblastic lymphoma, 2). The median (range) age was 31 (5–50) yr. Three patients (2 with ALL and another with BC-CML) had leukemic meningeosis at the time of diagnosis: 2 received IT depot cytarabine as adjuvant therapy after triple IT therapy (TIT) (BC-CML) and TIT plus cranial irradiation (ALL), whereas the remaining case (ALL) only received IT depot cytarabine. The remaining 7 patients (ALL, 4, lymphoblastic lymphoma, 2, and BC-LMC, 1) presented CNS relapse. CNS prophylaxis in these patients consisted of TIT plus cranial irradiation (2 patients with ALL), TIT (2 patients with ALL and 2 with lymphoblastic lymphoma), whereas the patient with BC-LMC did not receive any prophylaxis. IT depot cytarabine was administered as the only treatment for CNS relapse in one patient with ALL, as treatment of a second CNS relapse in 2 ALL patients and as adjuvant to other therapies in 4 patients (to TIT in other patient with ALL, to TIT plus radiotherapy in the patient with BC-CML, and to radiotherapy in the 2 patients with lymphoblastic lymphoma). In the 4 evaluable cases (one patient with ALL and CNS involvement at diagnosis and 3 patients with ALL and CNS relapse, 2 with second CNS relapse) treated with IT depot cytarabine as the only drug, clearance of blasts in cerebrospinal fluid (CSF) was observed with sustained response in two (at 7 and 22 months). The remaining 2 patients presented neurologic and systemic progression at 3 and 2 months, respectively. The median number of IT depot cytarabine administrations was 4 (1–9). Concurrent systemic dexamethasone therapy (4 mg twice/day/5 days) was administered with each dose of IT depot cytarabine. Side effects included headache (5 patients), dizziness (2) vomiting (2) and nausea (1). Depot formulation of cytarabine was effective in achieving CNS remission in ALL patients with CNS involvement or relapse. The administration of depot formulation of cytarabine was well tolerated. This justifies the development of a clinical trial to evaluate the efficacy and safety of IT depot cytarabine in meningeal involvement of ALL.