The central nervous system in childhood leukemia. II. Subacute leukoencephalopathy

A study was performed to evaluate the clinical and histopathologic characteristics of a distinctive degenerative lesion within the central nervous system (CNS) of children with acute lymphocytic leukemia (ALL). Of the 231 patients in this study, 13 were found to have specific degenerative changes in telencephalic white matter. Morphologically, the principal changes consisted of diffuse reactive astrocytosis and multiple, noninflammatory necrotic foci, often containing varying amount of mineralized cellular debris. Clinical features common to all patients with this leukoencephalopathy were: 1) cranial irradiation of 2000 rads or more and 2) methotrexate administered systemically after irradiation. Comparison of selected clinical features of patients with and without leukoencephalopathy showed that methotrexate administered intravenously after a cumulative dose of CNS irradiation of 2000 rads or more can result in degeneration of CNS white matter in patients with ALL. Age at time of irradiation, bacterial infections, nutrition, and CNS leukemia were not causally related to the development of this disease. This study suggests that chemotherapeutic agents may diffuse through the blood-brain barrier following CNS irradiation of 2000 rads or more.