Stenzel Stephanie L, Krull Kevin R, Hockenberry Marilyn, Jain Neelam, Kaemingk Kris, Miketova Petra, Moore Ida M
Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA.
J Pediatr Hematol Oncol. 2010 Mar;32(2):113-8. doi: 10.1097/MPH.0b013e3181c9af84.
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.
小儿急性淋巴细胞白血病(ALL)化疗后的神经行为问题是近期的研究重点。本研究扩展了先前的研究,通过检查氧化应激的早期标志物与后续神经行为问题的关系,提示氧化应激是化疗诱导中枢神经系统损伤的潜在机制。在87例ALL患儿诊断、诱导和巩固治疗时,测量其脑脊液中磷脂酰胆碱(PC)的氧化和未氧化成分。在巩固治疗后和化疗结束时进行行为评估。结果显示生理反应性(从诊断开始PC变化高与低)与行为结果(病理高与低)之间存在显著关联。氧化PC分数变化升高可预测治疗结束时攻击行为增加以及巩固治疗后的适应性。此外,多动症状随时间系统地变化,与未氧化PC和氧化PC分数反应性均有关。这些发现表明行为问题症状在化疗过程早期出现,诱导和巩固治疗期间脑脊液中氧化应激的PC标志物增加可能有助于预测某些未来的行为问题。