# Identifying children with subclinical neurocognitive decline and susceptibility to oxidative damage during the early months of therapy for ALL

> **NIH NIH R01** · RBHS -CANCER INSTITUTE OF NEW JERSEY · 2021 · $682,392

## Abstract

Project Summary/Abstract
Title: Identifying children with subclinical neurocognitive decline and susceptibility to oxidative
damage during the early months of therapy for ALL
This proposal is in response to Provocative Question 7, “How can prediction models be developed and used to
identify patients at highest risk of treatment related complications?” We have previously identified genetic
variants conferring susceptibility to oxidative stress that are associated with inferior cognitive function after
treatment for acute lymphoblastic leukemia (ALL). In preparation for a clinical trial testing whether antioxidant
therapy can protect against treatment-induced neurocognitive decline, we will test the hypothesis that leukemia
therapy induces oxidative damage and measurable neurocognitive decline among susceptible individuals
during the first months of ALL therapy. The proposed prediction model will therefore identify patients with
childhood ALL at a time when a proactive intervention might prevent permanent treatment-induced cognitive
deficits. We will test this hypothesis in three related Specific Aims: (1) Prospectively demonstrate that
subclinical treatment-induced changes in cognitive function can be detected in the first three months of
treatment for ALL and predict dysfunction 1 year after treatment among children being treated for ALL on Dana
Farber Cancer Institute ALL Consortium protocol 16-001 at eight sites in the United States and Canada; (2)
Prospectively demonstrate relationships between treatment-induced changes in neurocognitive functioning and
targeted polymorphisms in genes conferring susceptibility to oxidative stress. and (3) Prospectively identify
relationships between gene variants and changes in biomarkers indicative of oxidative damage within the
central nervous system. Neurocognitive function will be assessed using a well-validated computer-based
instrument (Cogstate) at multiple time points during the two years of therapy and one year after completion of
treatment, allowing detection of subclinical changes in neurocognitive abilities from baseline. Latent Class
Mixture Modeling will be used to resolve distinct patterns of change in performance over time, and patterns of
changes from baseline during the first months of treatment will be linked to deficits persisting among survivors
more than one year after completion of treatment. This project will therefore identify patients with treatment-
related changes in neurocognitive function (Aim 1) at a point in therapy when an intervention might prevent
further decline. In addition, the project complements our laboratory efforts to understand the pathophysiology
of treatment-related cognitive decline, by testing the relationship between variants in genes related to oxidative
stress and cognitive decline (Aim 2) and biomarkers of oxidative damage (Aim 3). Thus, the results obtained
from this proposal are expected to have a positive impact because they will provide the foundation to ...

## Key facts

- **NIH application ID:** 10249976
- **Project number:** 5R01CA220568-04
- **Recipient organization:** RBHS -CANCER INSTITUTE OF NEW JERSEY
- **Principal Investigator:** Peter D. Cole
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $682,392
- **Award type:** 5
- **Project period:** 2018-09-17 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10249976

## Citation

> US National Institutes of Health, RePORTER application 10249976, Identifying children with subclinical neurocognitive decline and susceptibility to oxidative damage during the early months of therapy for ALL (5R01CA220568-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10249976. Licensed CC0.

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