Abstract

Treatment of CNS involvement in patients with AML is based on repetead intrathecal (IT) administrations of chemotherapy, especially methotrexate and cytarabine, until to achieve clearance of blast cells from cerebrospinal fluid (CSF). Recently, the availability of a depot formulation of liposomal cytarabine (DepoCyte®), administered every two weeks by IT route, has demonstrated to be useful for the treatment of neoplastic and lymphomatous meningitis. However, there are few studies that have analyzed its efficacy in the prophylaxis and treatment of CNS involvement in patients with AML. A retrospective review was performed of all cases in which IT depot cytarabine was employed as compassionate therapy for CNS involvement of AML in Spain and United Kingdom. From March 2004 to April 2006, 11 AML cases (2 with acute promyelocytic leukemia [APL]) were recorded. The median (range) age was 46 (18–57) yr and there were 7 females. Six patients had CNS involvement at the time of the diagnosis and the remaining had CNS relapse (first CNS relapse in 4, 2nd relapse in 1). Four out of 6 patients with initial involvement received IT depot cytarabine after one dose of triple IT therapy (TIT) administered during the screening lumbar puncture (one patient received two TIT doses), another received cranial irradiation in addition to IT depot cytarabine, and the remaining was treated only with IT depot cytarabine. The 5 patients with CNS relapse received one TIT dose plus IT depot cytarabine in 3 cases, cranial irradiation plus IT depot cytarabine in one, and only IT depot cytarabine in the remaining. Complete resolution of neurological symptoms was observed in 9 cases and partial response in the remaining 2, whereas clearance of blasts from CSF was observed in 7 evaluable cases. Sustained response was observed in 6 patients (median follow-up 6 [4–23] months) whereas the remaining 5 died from infection (3) or systemic relapse (2), without evidence of neurological progression. The median number of IT depot cytarabine administrations was 3 (1–10). Concurrent dexamethasone therapy (4 mg twice/day/5 days) was administered with each dose of IT depot cytarabine. Side effects included headache (3 patients), fever (1) vomiting (1) and nausea (1). Depot formulation of cytarabine was effective to obtain clearance of blasts cells from CSF in AML 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 AML.

Disclosure: No relevant conflicts of interest to declare.

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