A case of two repeated CNS recurrences of acute non-
lymphocytic leukemia (M2) was treated with intermediate dose
Ara-C therapy and achieved 2 complete remissions. The clinical effect and pharmacokinetics of intermediate dose
Ara-C therapy in this patient were discussed. A 55-year-old male with acute non-
lymphocytic leukemia (M2) achieved complete remission by
combination chemotherapy of
Behenoyl-ara-C,
Daunorubicin,
6-Mercaptopurine and
Prednisolone in July, 1985. He subsequently received consolidation and intensification
therapy with periodical
intrathecal injection of
Methotrexate (MTX), but 13 months later he developed his first CNS recurrence which was resistant to the intrathecal administration of
Ara-C and MTX. As he also relapsed systemically,
Ara-C was administered in intermediate dose (1 g/m2 every 12 hrs for 5 days) and he achieved complete remission both in the CNS and systemic manifestations. Six months later he was diagnosed as having a second CNS recurrence and another systemic relapse. Intermediate dose
Ara-C was administered again, and he achieved complete remission in the CNS and partial remission in systemic manifestations. Pharmacokinetic study revealed high peaks of
Ara-C concentration in plasma (6.2 microM immediately after the end of the infusion) and high degree of its penetration into the CNS (5.6 microM at 3 hr after the end of the infusion) suggesting the effective and perhaps a uniform level of
Ara-C is achieved throughout the CNS by this
therapy. In 3 other patients without CNS involvement 0.88 +/- 0.44 microM of
Ara-C, which is enough concentrations for its
cytostatic effect, was detected at 3 hr after the end of infusion, suggesting the efficacy of the
therapy for CNS prophylaxis. In this case the relapse occurred after repeated administration of antileukemic drugs, including
Behenoyl-ara-C, an analog of
Ara-C, and was resistant to the intrathecal administration of
Ara-C. These findings suggest that intermediate dose
Ara-C therapy was effective to overcome a resistance to antileukemic drugs, including
Ara-C, and also, in some cases, more effective than
intrathecal injection of antileukemic drugs for the treatment of CNS
leukemia.