BACKGROUND: Neurocognitive sequelae following treatment for pediatric acute lymphoblastic leukemia (ALL) has been reported in a significant proportion of survivors, including those treated only with chemotherapy. Early identification of children "at risk" for neurocognitive problems is not yet reliable. Biomarkers of oxidative stress (e.g., oxidated phosphatidylcholine) in cerebral spinal fluid (CSF) have been correlated with intensity of methotrexate (MTX) treatment, suggesting an association with acute central nervous system toxicity. PROCEDURE: This study examined the association between oxidized CSF phospholipids and executive functions throughout chemotherapy. Measures of oxidative stress and executive functions were examined in 88 children newly diagnosed with ALL. The children were followed over 3 years with neurocognitive testing and parent ratings of executive functions. RESULTS: Results demonstrated an association between increased oxidative stress following induction and consolidation and decreased executive function 2 years later. Younger age at diagnosis was associated with both an increase in oxidative stress and in executive dysfunction; younger age was associated with poorer ability to organize materials in one's environment (r(48) = 0.28, P < 0.05) and with greater oxidated phosphatidylcholine in CSF at the end of chemotherapy (r(48) = -0.27, P < 0.05). As such, younger age appears to be the most prominent moderator of neurocognitive decline. CONCLUSIONS: These results link functional changes to CSF biomarkers and underscore the importance of monitoring cognitive development in young children treated for ALL. Children with less advanced central nervous system development may be particularly vulnerable to the effects of chemotherapy.
BACKGROUND:Neurocognitive sequelae following treatment for pediatric acute lymphoblastic leukemia (ALL) has been reported in a significant proportion of survivors, including those treated only with chemotherapy. Early identification of children "at risk" for neurocognitive problems is not yet reliable. Biomarkers of oxidative stress (e.g., oxidated phosphatidylcholine) in cerebral spinal fluid (CSF) have been correlated with intensity of methotrexate (MTX) treatment, suggesting an association with acute central nervous system toxicity. PROCEDURE: This study examined the association between oxidized CSF phospholipids and executive functions throughout chemotherapy. Measures of oxidative stress and executive functions were examined in 88 children newly diagnosed with ALL. The children were followed over 3 years with neurocognitive testing and parent ratings of executive functions. RESULTS: Results demonstrated an association between increased oxidative stress following induction and consolidation and decreased executive function 2 years later. Younger age at diagnosis was associated with both an increase in oxidative stress and in executive dysfunction; younger age was associated with poorer ability to organize materials in one's environment (r(48) = 0.28, P < 0.05) and with greater oxidated phosphatidylcholine in CSF at the end of chemotherapy (r(48) = -0.27, P < 0.05). As such, younger age appears to be the most prominent moderator of neurocognitive decline. CONCLUSIONS: These results link functional changes to CSF biomarkers and underscore the importance of monitoring cognitive development in young children treated for ALL. Children with less advanced central nervous system development may be particularly vulnerable to the effects of chemotherapy.
Authors: Paul C Nathan; Sunita K Patel; Kimberley Dilley; Robert Goldsby; Jeanne Harvey; Chad Jacobsen; Nina Kadan-Lottick; Karen McKinley; Anne K Millham; Ida Moore; M Fatih Okcu; Catherine L Woodman; Pim Brouwers; F Daniel Armstrong Journal: Arch Pediatr Adolesc Med Date: 2007-08
Authors: Marilyn Hockenberry; Kevin Krull; Ki Moore; Mary Ann Gregurich; Marissa E Casey; Kris Kaemingk Journal: J Pediatr Hematol Oncol Date: 2007-08 Impact factor: 1.289
Authors: Brenda J Spiegler; Kimberly Kennedy; Ronnen Maze; Mark L Greenberg; Sheila Weitzman; Johann K Hitzler; Paul C Nathan Journal: J Clin Oncol Date: 2006-08-20 Impact factor: 44.544
Authors: Deborah P Waber; Jennifer Turek; Lori Catania; Kristen Stevenson; Philippe Robaey; Ivonne Romero; Heather Adams; Cheryl Alyman; Christine Jandet-Brunet; Donna S Neuberg; Stephen E Sallan; Lewis B Silverman Journal: J Clin Oncol Date: 2007-11-01 Impact factor: 44.544
Authors: Ida M Ki Moore; Petra Miketova; Marilyn Hockenberry; Kevin Krull; Alice Pasvogel; Marissa Carey; Kris Kaemingk Journal: Biol Res Nurs Date: 2008-04 Impact factor: 2.522
Authors: Nicholas S Phillips; Yin Ting Cheung; John O Glass; Matthew A Scoggins; Wei Liu; Robert J Ogg; Daniel A Mulrooney; Ching-Hon Pui; Leslie L Robison; Wilburn E Reddick; Melissa M Hudson; Kevin R Krull Journal: Pediatr Blood Cancer Date: 2019-08-12 Impact factor: 3.167
Authors: Olga A Taylor; Marilyn J Hockenberry; Kathy McCarthy; Patricia Gundy; David Montgomery; Adam Ross; Michael E Scheurer; Ida M Moore Journal: J Pediatr Oncol Nurs Date: 2015-01-30 Impact factor: 1.636
Authors: Yin Ting Cheung; Raja B Khan; Wei Liu; Tara M Brinkman; Michelle N Edelmann; Wilburn E Reddick; Deqing Pei; Angela Panoskaltsis-Mortari; Deokumar Srivastava; Cheng Cheng; Leslie L Robison; Melissa M Hudson; Ching-Hon Pui; Kevin R Krull Journal: JAMA Oncol Date: 2018-07-12 Impact factor: 31.777
Authors: Marilyn J Hockenberry; Olga A Taylor; Patricia M Gundy; Adam K Ross; Alice Pasvogel; David Montgomery; Phillip Ribbeck; Kathy McCarthy; Ida Moore Journal: Biol Res Nurs Date: 2013-08-15 Impact factor: 2.522
Authors: Yin Ting Cheung; Michelle N Edelmann; Daniel A Mulrooney; Daniel M Green; Wassim Chemaitilly; Neena John; Leslie L Robison; Melissa M Hudson; Kevin R Krull Journal: Cancer Epidemiol Biomarkers Prev Date: 2016-06-26 Impact factor: 4.254