THE ROLE OF SYSTEMIC HIGH-DOSE CYTARABINE IN THE TREATMENT OF CENTRAL-NERVOUS-SYSTEM LEUKEMIA - CLINICAL-RESULTS IN 46 PATIENTS

Background. Given the good penetration of systemic high-dose cytarabin e (HDara-C) into the cerebrospinal fluid (CSF), this approach was used to treat patients with central nervous system (CNS) leukemia, either isolated or with concurrent extraneurologic disease (END). Methods. Fr om 1983 to 1991, 46 adults with CNS involvement were treated with syst emic HDara-C: 25 had acute lymphoblastic leukemia (ALL), 15 had high-g rade non-Hodgkin lymphoma (NHL), 5 had acute myelogenous leukemia (AML ), and 1 had lymphoid blast crisis of chronic myelogenous leukemia. In duction consisted of HDara-C 3 g/m2 every 12 hours, by 3-hour infusion , for 8 doses (30 patients), or 6 doses (16 patients), followed by 4 d oses at day 21. Results. Of 46 patients, 29 (63%) achieved complete re mission (CR): 15/15 with isolated CNS leukemia, and 14/31 (45%) with C NS and concurrent marrow or lymph node disease. Of 17 patients not mee ting CR criteria because of persistent END, 11 showed complete CNS res ponse. The first 10 remitters were consolidated with monthly 4-dose co urses of HDara-C. The remaining 19 received postinduction multidrug ch emotherapy (including vincristine, doxorubicin, cyclophosphamide, L-as paraginase, etoposide plus intermediate-dose ara-C, mitoxantrone plus HDara-C) and intrathecal methotrexate (MTX) +/- cranial radiation ther apy. One patient underwent autologous and one allogeneic bone marrow 2 -56+): 8 months for patients with isolated CNS leukemia, and 4 months for those with concurrent END. In only two patients was CNS the primar y site of relapse. Three patients with isolated CNS leukemia are disea se-free at 23, 40, and 56 months. The main toxicity was myelosuppressi on. No patient showed dose-limiting neurologic toxicity. Conclusions. Systemic HDara-C appears effective therapy for CNS leukemia, maximally in cases with isolated CNS involvement. HDara-C may be combined safel y with cranial radiation therapy and intrathecal MTX. This approach fo r CNS leukemia, however, needs to be combined with additional treatmen ts to eradicate residual disease in extraneurologic compartments.