Hockenberry Marilyn J, Taylor Olga A, Gundy Patricia M, Ross Adam K, Pasvogel Alice, Montgomery David, Ribbeck Phillip, McCarthy Kathy, Moore Ida
Duke School of Nursing, Durham, NC, USA
Baylor College of Medicine, Houston, TX, USA.
Biol Res Nurs. 2014 Jul;16(3):303-9. doi: 10.1177/1099800413498507. Epub 2013 Aug 15.
Acute lymphoblastic leukemia (ALL) is the most prevalent and curable cancer among children and adolescents less than 15 years of age in the United States. Essential for cure of childhood ALL is prophylactic treatment of the central nervous system (CNS), with methotrexate (MTX) being the most widely used drug in this treatment. While CNS treatment has contributed to long-term disease-free survival, resulting declines in academic abilities have been reported. There is growing evidence that CNS treatment with MTX increases oxidative stress, a potential mechanism of CNS injury. This article reports changes in oxidative stress, measured by the biomarker F2-isoprostane (F2-IsoP), in the cerebrospinal fluid (CSF) in 47 children with ALL during the first 18 months of treatment. The number of CSF samples ranged from 5 to 14 during postinduction and from 1 to 9 during continuation. Total doses of intrathecal MTX during postinduction were significantly correlated with the mean and highest concentrations of F2-IsoP during postinduction and the mean concentration of F2-IsoP during continuation. F2-IsoP concentrations during postinduction and continuation were higher in children who received more than six doses of intrathecal MTX. New therapies for a highly curable disease such as childhood leukemia have the potential to be individualized in the future, requiring reliable molecular and biochemical markers, such as oxidative stress indicators. Innovative use of biomarkers has the potential to increase our understanding of treatment-related toxicities and associated symptoms and to inform future therapeutic approaches for optimizing cure and quality of life among children with leukemia.
急性淋巴细胞白血病（ALL）是美国15岁以下儿童和青少年中最常见且可治愈的癌症。中枢神经系统（CNS）的预防性治疗是儿童ALL治愈的关键，甲氨蝶呤（MTX）是该治疗中使用最广泛的药物。虽然CNS治疗有助于实现长期无病生存，但已有报道称其会导致学业能力下降。越来越多的证据表明，用MTX进行CNS治疗会增加氧化应激，这是CNS损伤的一种潜在机制。本文报告了47例ALL患儿在治疗的前18个月期间，通过生物标志物F2 -异前列腺素（F2-IsoP）测量的脑脊液（CSF）中氧化应激的变化。诱导后CSF样本数量为5至14个，维持期为1至9个。诱导后鞘内注射MTX的总剂量与诱导后F2-IsoP的平均浓度和最高浓度以及维持期F2-IsoP的平均浓度显著相关。接受超过6剂鞘内MTX的儿童在诱导后和维持期的F2-IsoP浓度较高。对于像儿童白血病这样高度可治愈的疾病，新疗法未来有可能实现个体化，这需要可靠的分子和生化标志物，如氧化应激指标。生物标志物的创新性应用有可能增进我们对治疗相关毒性及相关症状的理解，并为优化白血病患儿的治愈效果和生活质量提供未来的治疗方法参考。
