original paper

Central nervous system involvement is a well-recognized complication of acute lympho-cytic leukemia (ALL) ranging between 20 and 40 % of cases, and its prophylaxis has greatly reduced the incidence of CNSL as primary site of recurrence in adults.1-3 On the contrary, due to the low frequency of CNS involvement in AML (2-4%)4-6 prophylactic therapy is still controversial, although an overt meningeal leukemia, especially with con-current systemic disease, still represents a major therapeutic problem. Conventional treatment of CNSL consists of intrathecal (IT) chemotherapy with methotrexate (MTX) and/or cytarabine (Ara-C) plus meningeal irradiation.7 Although this approach is usually effective in clearing cerebrospinal fluid, the remis-sions are usually short-lived.8 Furthermore, CNS involvement is often followed by bone marrow (BM)1 recurrence, which is consistent with the hypothesis that CNS represents a sanctuary for leukemia blasts that eventually repopulate the BM.9 Therefore, a systemic chemotherapy appears more appropriate in treating CNSL both in ALL or AML; in particular, systemic high dose Ara-C (HD Ara-C) can be used alone or in combination with other therapeutic approaches. In fact, systemic HD Ara-C, which is active in resistant acute leukemia and non-Hodgkin’s lymphoma, crosses the blood brain barrier achieving significant levels in the cerebral spinal fluid (CSF), thus permitting a more uniform distribution of the drug throughout the neuraxis.10 In addition, due to the low levels of cytidine deami-nase in the CNS, Ara-C catabolism in the CSF is lower than in the peripheral blood, which results in prolonged therapeutic levels of the drug.11,12 On the basis of these observations, we used HD Ara-C in association with IT MTX with or without cranial irradiation, to treat 9 adult patients with AML and CNS involvement. We report herein the results of this combined approach