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Oxidative Stress and Neurobehavioral Problems in Pediatric Acute Lymphoblastic Leukemia Patients Undergoing Chemotherapy

Stenzel, Stephanie L. MPH*; Krull, Kevin R. PhD; Hockenberry, Marilyn PhD; Jain, Neelam PhD; Kaemingk, Kris PhD§; Miketova, Petra PhD; Moore, Ida M. DNS

Journal of Pediatric Hematology/Oncology: March 2010 - Volume 32 - Issue 2 - p 113-118
doi: 10.1097/MPH.0b013e3181c9af84
Original Articles

Neurobehavioral problems after chemotherapy treatment for pediatric acute lymphoblastic leukemia (ALL) have been a recent focus of investigation. This study extended previous research that suggested oxidative stress as a potential mechanism for chemotherapy-induced central nervous system injury by examining early markers of oxidative stress in relation to subsequent neurobehavioral problems. Oxidized and unoxidized components of phosphatidylcholine (PC) were measured in the cerebrospinal fluid of 87 children with ALL at diagnosis, induction, and consolidation. Behavioral assessments were conducted postconsolidation and at the end of chemotherapy. Results revealed a significant association between physiologic reactivity (high vs. low PC changes from diagnosis) and behavioral outcomes (high vs. low pathology). Elevated oxidized PC fraction change was predictive of increased problems with aggression at the end of therapy as well as postconsolidation adaptability. Furthermore, symptoms of hyperactivity systematically changed over time in relation to both unoxidized PC and oxidized PC fraction reactivity. These findings suggest that symptoms of behavioral problems occur early in the course of chemotherapy and that increases in the cerebrospinal fluid PC markers of oxidative stress during induction and consolidation may help to predict certain future behavioral problems.

*Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI

Department of Epidemiology & Cancer Control, St. Jude Children's Research Hospital, Memphis, TN

Department of Pediatrics, Baylor College of Medicine, Houston, TX

§Private Practice

Department of Pediatrics, University of Arizona, Phoenix, AZ

Supported in part by NIH grants HD 37816 (K. Kaemingk) and NR 04905 (I. M. Moore).

Reprints: Kevin R. Krull, PhD, Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS 735, Memphis, TN 38105-2799 (e-mail:

Received for publication January 22, 2009

accepted November 5, 2009

© 2010 Lippincott Williams & Wilkins, Inc.