title: Feasibility of baseline neurocognitive assessment using Cogstate during the first month of therapy for childhood leukemia.
abstract: Neurocognitive impairment is frequently observed among acute lymphoblastic leukemia (ALL) survivors within the domains of intelligence, attention, processing speed, working memory, learning, and memory. However, few have investigated treatment-induced changes in neurocognitive function during the first months of treatment. Additionally, dysfunction during treatment may be preceded by changes in biomarkers measured within cerebrospinal fluid (CSF). Identification of acute declines in neurocognitive function, as well as predictive genotypes or biomarkers, could guide therapeutic trials of protective interventions.
  
  
  
  This study collects CSF while prospectively assessing neurocognitive functioning (working memory, executive function, learning, processing speed, and attention) of ALL patients using the Cogstate computerized battery at six time points during and after the 2 years of leukemia treatment on a Dana-Farber Cancer Institute ALL Consortium trial.
  
  
  
  Baseline data collected during the first 3 weeks of induction chemotherapy indicate reliable data as all subjects (N = 34) completed Cogstate baseline testing, while completion and performance checks indicate that 100 % of subjects completed testing and complied with test requirements. The majority (85 %) exhibited normal function compared with age peers. Preliminary analysis of CSF biomarkers (folate, homocysteine, 8-isoprostane, and myelin basic protein) similarly reveals values at baseline within expected normal ranges.
  
  
  
  The first month of induction therapy for ALL is a reliable baseline for detecting treatment-induced changes in neurocognitive functioning. Consequently, serial data collection might identify subgroups of ALL patients at increased risk for neurocognitive decline, warranting proactive interventions to improve their level of functioning both during treatment and into survivorship.
authors.affiliation: Division of Pediatric Hematology, Oncology, and Stem Cell Transplantation, Columbia University Medical Center, 161 Fort Washington Avenue, New York, NY, USA. sandss@mskcc.org.|Division of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, 641 Lexington Avenue 7th Floor, New York, NY, 10022, USA. sandss@mskcc.org.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Sands
authors.affiliation: Cogstate, Inc., 195 Church Street, New Haven, CT, USA.|Yale School of Medicine, Yale Child Study Center, 230 South Frontage Rd, New Haven, CT, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Harel
authors.affiliation: Division of Pediatric Hematology, Oncology, and Stem Cell Transplantation, Columbia University Medical Center, 161 Fort Washington Avenue, New York, NY, USA.
authors.forename: Mirko
authors.initials: M
authors.lastname: Savone
authors.affiliation: Division of Pediatric Hematology, Oncology, and Stem Cell Transplantation, Columbia University Medical Center, 161 Fort Washington Avenue, New York, NY, USA.
authors.forename: Kara
authors.initials: K
authors.lastname: Kelly
authors.affiliation: Department of Pediatrics, Albert Einstein College of Medicine, 3415 Bainbridge Avenue, Bronx, NY, USA.
authors.forename: Veena
authors.initials: V
authors.lastname: Vijayanathan
authors.affiliation: Division of Pediatric Hematology/Oncology, Department of Pediatrics, Alpert Medical School of Brown University, Providence, RI, USA.
authors.forename: Jennifer Greene
authors.initials: JG
authors.lastname: Welch
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute/Division of Pediatric Hematology-Oncology, Boston Children's Hospital, 450 Brookline Avenue, Boston, MA, USA.
authors.forename: Lynda
authors.initials: L
authors.lastname: Vrooman
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute/Division of Pediatric Hematology-Oncology, Boston Children's Hospital, 450 Brookline Avenue, Boston, MA, USA.
authors.forename: Lewis B
authors.initials: LB
authors.lastname: Silverman
authors.affiliation: Department of Pediatrics, Albert Einstein College of Medicine, 3415 Bainbridge Avenue, Bronx, NY, USA.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Cole
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D001288:Attention / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000134:cerebrospinal fluid*; D002648:Child; D002675:Child, Preschool; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000134:cerebrospinal fluid / Q000139:chemically induced / Q000175:diagnosis* / Q000209:etiology; D056344:Executive Function / Q000187:drug effects; D005260:Female; D006801:Humans; D007278:Injections, Spinal; D008297:Male; D008568:Memory / Q000187:drug effects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000134:cerebrospinal fluid* / Q000188:drug therapy* / Q000523:psychology; D017741:Survivors; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor
keywords: Acute lymphoblastic leukemia; Biomarkers; Late effects; Methotrexate; Neurocognitive; Neurotoxicity