The role of systemic high-dose cytarabine in the treatment of central nervous system leukemia. Clinical results in 46 patients

Abstract

Background: Given the good penetration of systemic high-dose cytarabine (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: From 1983 to 1991, 46 adults with CNS involvement were treated with systemic HDara-C: 25 had acute lymphoblastic leukemia (ALL), 15 had high-grade non-Hodgkin lymphoma (NHL), 5 had acute myelogenous leukemia (AML), and 1 had lymphoid blast crisis of chronic myelogenous leukemia. Induction 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 doses at day 21.

Results: Of 46 patients, 29 (63%) achieved complete remission (CR): 15/15 with isolated CNS leukemia, and 14/31 (45%) with CNS and concurrent marrow or lymph node disease. Of 17 patients not meeting CR criteria because of persistent END, 11 showed complete CNS response. The first 10 remitters were consolidated with monthly 4-dose courses of HDara-C. The remaining 19 received postinduction multidrug chemotherapy (including vincristine, doxorubicin, cyclophosphamide, L-asparaginase, etoposide plus intermediate-dose ara-C, mitoxantrone plus HDara-C) and intrathecal methotrexate (MTX) +/- cranial radiation therapy. One patient underwent autologous and one allogeneic bone marrow transplant. Median CR duration was 7 months (range, 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 primary site of relapse. Three patients with isolated CNS leukemia are disease-free at 23, 40, and 56 months. The main toxicity was myelosuppression. 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 safely with cranial radiation therapy and intrathecal MTX. This approach for CNS leukemia, however, needs to be combined with additional treatments to eradicate residual disease in extraneurologic compartments.