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Feasibility of baseline neurocognitive assessment using Cogstate during the first month of therapy for childhood leukemia

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

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Acknowledgments

Patients were enrolled at the following sites: Columbia University Medical Center, New York, NY; The Children’s Hospital at Montefiore, Bronx, NY; Dana-Farber Cancer Institute/Boston Children’s Hospital, Boston, NY; and Hasbro Children’s Hospital, Providence, RI. This work was supported in part by NIH/NCI R21-CA187226.

Author information

Authors and Affiliations

  1. Division of Pediatric Hematology, Oncology, and Stem Cell Transplantation, Columbia University Medical Center, 161 Fort Washington Avenue, New York, NY, USA

    Stephen A. Sands, Mirko Savone & Kara Kelly

  2. Division of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, 641 Lexington Avenue 7th Floor, New York, NY, 10022, USA

    Stephen A. Sands

  3. Cogstate, Inc., 195 Church Street, New Haven, CT, USA

    Brian T. Harel

  4. Yale School of Medicine, Yale Child Study Center, 230 South Frontage Rd, New Haven, CT, USA

    Brian T. Harel

  5. Department of Pediatrics, Albert Einstein College of Medicine, 3415 Bainbridge Avenue, Bronx, NY, USA

    Veena Vijayanathan & Peter D. Cole

  6. Division of Pediatric Hematology/Oncology, Department of Pediatrics, Alpert Medical School of Brown University, Providence, RI, USA

    Jennifer Greene Welch

  7. Department of Pediatric Oncology, Dana-Farber Cancer Institute/Division of Pediatric Hematology-Oncology, Boston Children’s Hospital, 450 Brookline Avenue, Boston, MA, USA

    Lynda Vrooman & Lewis B. Silverman

Authors
  1. Stephen A. Sands
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  9. Peter D. Cole
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Corresponding author

Correspondence to Stephen A. Sands.

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Conflict of interest

The authors declare that they have no conflict of interest, with the exception of Brian Harel who was an employee and a stockholder of Cogstate until February 2016.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Sands, S.A., Harel, B.T., Savone, M. et al. Feasibility of baseline neurocognitive assessment using Cogstate during the first month of therapy for childhood leukemia. Support Care Cancer 25, 449–457 (2017). https://doi.org/10.1007/s00520-016-3422-9

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  • DOI: https://doi.org/10.1007/s00520-016-3422-9

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