Neurocognitive and psychosocial outcomes in survivors of childhood leukemia with Down syndrome

Abstract

Objective: The primary aim of this study was to assess the feasibility of a developmentally tailored neurocognitive assessment in survivors of childhood acute leukemia with Down syndrome (DS-leukemia). A secondary aim was to compare outcomes in the DS-leukemia group to a historical comparison group of individuals with DS and no history of childhood cancer.

Methods: Survivors of DS-leukemia (n = 43; 56% male, mean [SD] age at diagnosis = 4.3 [4.5] years; age at evaluation = 15 [7.9] years) completed a neurocognitive assessment battery that included direct measures of attention, executive function, and processing speed, and proxy ratings of attention problems and executive dysfunction. Direct assessment outcomes were compared to a historical comparison cohort of individuals with DS and no history of childhood cancer (DS-control; n = 117; 56% male, mean [SD] age at evaluation = 12.7 [3.4] years).

Results: Rates of valid task completion ranged from 54% to 95%, suggesting feasibility for most direct assessment measures. Compared to the DS-control group, the DS-leukemia group had significantly lower completion rates on measures of executive function (p = 0.008) and processing speed (p = 0.018) compared to the DS-control group. There were no other significant group differences in completion rates. Compared to the DS-control group, the DS-leukemia group had significantly more accurate performance on two measures of executive function (p = 0.032; p = 0.005). Compared to the DS-control group, the DS-leukemia group had significantly more problems with executive function as identified on proxy ratings (6.5% vs. 32.6%, p = <0.001).

Conclusion: Children with Down syndrome (DS) are at increased risk for developing acute leukemia compared to the general population but are systematically excluded from neurocognitive outcome studies among leukemia survivors. This study demonstrated the feasibility of evaluating neurocognitive late effects in leukemia survivors with DS using novel measures appropriate for populations with intellectual developmental disorder.

Keywords: childhood ALL; neurocognitive late effects; quality of life; survivorship.

FIGURE 1

Study flow chart. Study population is survivors of DS‐leukemia treated at St. Jude Children’s Research Hospital between 1980 and 2015.

FIGURE 2

Frequency of caregiver ratings of attention problems and executive dysfunction for the DS‐leukemia and DS‐control groups. BRIEF Scales: Global Executive, Inhibit, Working Memory, Shift, Emotion Regulation, Plan/Organize. CBCL Scale: Attention Problems. Scores are considered clinically significant if they are ≥2 standard deviations above the normative mean, with higher scores indicating more problems. The expected frequency of clinically significant elevations in the normative population is 7%. Two‐sided p‐values are from chi‐square frequency comparisons between the DS‐leukemia and DS‐control groups.

FIGURE 3

Frequency of caregiver ratings of attention problems and executive dysfunction for the DS‐ALL and DS‐AML groups. BRIEF Scales: Global Executive, Inhibit, Working Memory, Shift, Emotion Regulation, Plan/Organize. CBCL Scale: Attention Problems. Scores are considered clinically significant if they are ≥2 standard deviations above the normative mean, with higher scores indicating more problems. The expected frequency of clinically significant elevations in the normative population is 7%. Two‐sided p‐values are from chi‐square frequency comparisons between the DS‐leukemia and DS‐control groups.