Central nervous system (CNS) treatment contributes to improved long-term disease-free survival from childhood acute lymphoblastic leukemia (ALL) by sigificantly decreasing the rate of disease relapse. Methotrexate (MTX), a drug commonly used for CNS treatment, has been associated with cognitive and academic problems, white-matter changes, perfusion defects, and brain atrophy. This study investigated oxidative stress as a possible mechanism of chemotherapyinduced CNS injury. Unoxidized and oxidized components of phosphatidylcholine (PC), the most prevalent phospholipid in CNS cellular membranes, were measured in cerebral spinal fluid (CSF) samples obtained from 21 children diagnosed with low (n = 7), standard (n= 7), or high (n= 7) risk ALL. Children with high-risk ALL received the most MTX, especially during the most intensive phase of treatment (consolidation). Phospholipids were extracted from CSF samples obtained at diagnosis and during the induction, consolidation, and continuation treatment phases. Unoxidized and oxidized PC were measured by normalphase high-performance liquid chromatography at 2 ultraviolet wavelengths (206 and 234 nm, respectively). Data were analyzed by 2-way repeated-measures analysis of variance. Results support the hypotheses that the highest levels of oxidized PC would be observed during the most intensive phase of ALL therapy and in the high-risk ALL group. Findings provide preliminary evidence for chemotherapy-induced oxidative stress inCNSmembrane phospholipids.
Neurologic deficit in patients at high risk with thoracoabdominal aortic aneurysms: The role of cerebral spinal fluid drainage and distal aortic perfusion
