High dose Ara-C related leukoencephalopathy

Two patients with acute myelomonocytic leukemia in central nervous system relapse developed clinical signs and computerized tomographic evidence of leukoencephalopathy five to seven days after intravenous high dose Ara-C therapy. The first patient had received 30 gm of intravenous Ara-C with cranial irradiation (1680 rad in 2 fractions) and intrathecal Ara-C (100 mg X twice) for an intracerebral chloroma and leptomeningeal leukemia. In this patient the leukoencephatlopathy was probably a result of a synergistic effect of the concomitant triple therapy. The second patient had received intrathecal administration of Ara-C and methotrexate for five and one-half months prior to intravenous Ara-C therapy. He developed altered mental status after 24 gm of intravenous Ara-C infusion. CT scan showed changes in the white matter compatible with leukoencephalopathy. In this patient the intravenous Ara-C probably was the precipitating factor of the development of leukoencephalopathy. The possible mechanism of the Ara-C induced leukoencephalopathy is discussed.