Considering the good penetration of systemic high-dose
ara-C (HDara-C) into the CNS, we used this approach for treating overt meningeal
leukemia, either isolated or with concurrent extraneurologic disease, in 15 adults with high-risk
acute lymphoblastic leukemia (ALL), one adult with lymphoid
blast crisis of
chronic granulocytic leukemia (LBC-CGL), and four adults with poor-prognosis
non-Hodgkin's lymphoma (NHL). Treatment consisted of
ara-C, 3 g/m2 every 12 hours by three-hour infusion for eight doses followed by a second course of four doses on day 21. Remitters received consolidation with monthly courses of HDara-C for four doses. Additional systemic multi-
drug reinduction
therapy and direct CNS treatment with intrathecal
methotrexate (IT MTX) and
cranial irradiation (CRT) was administered to the three remitters last treated. Thirteen of 20 patients (65%) achieved complete remission (CR): seven of seven patients with isolated meningeal
leukemia and six of 13 patients with concurrent CNS and
bone marrow disease. Of the remaining seven patients, five had a complete CSF clearing with persistent marrow disease. In all cases there was prompt resolution of
neurologic signs and symptoms. The median duration of CR was 5 months (range 2 to 8 months). The most significant toxicity seen was myelosuppression, which was predictable and manageable. Nonhematologic toxicity was generally acceptable and included moderate
nausea and
vomiting,
diarrhea,
drug fever, transient
liver dysfunction, and
dermatitis. No cases of CNS toxicity occurred. There were no treatment-related deaths. Disease-free survival was limited by marrow relapse, either isolated or with concurrent
CNS disease. No instances of isolated meningeal relapse occurred. These results obtained in a poor-risk subset of patients indicate that HDara-C is an effective treatment for the
induction of remission in ALL and NHL with meningeal
leukemia. Therefore, HDara-C should be considered for inclusion in multiagent consolidation programs for patients at high risk for
CNS disease.