Neurocognitive outcomes decades after treatment for childhood acute lymphoblastic leukemia: a report from the St Jude lifetime cohort study

Abstract

Purpose: To determine rates, patterns, and predictors of neurocognitive impairment in adults decades after treatment for childhood acute lymphoblastic leukemia (ALL).

Patients and methods: Survivors of childhood ALL treated at St Jude Children's Research Hospital who were still alive at 10 or more years after diagnosis and were age ≥ 18 years were recruited for neurocognitive testing. In all, 1,014 survivors were eligible, 738 (72.8%) agreed to participate, and 567 (76.8%) of these were evaluated. Mean age was 33 years; mean time since diagnosis was 26 years. Medical record abstraction was performed for data on doses of cranial radiation therapy (CRT) and cumulative chemotherapy. Multivariable modeling was conducted and glmulti package was used to select the best model with minimum Akaike information criterion.

Results: Impairment rates across neurocognitive domains ranged from 28.6% to 58.9%, and those treated with chemotherapy only demonstrated increased impairment in all domains (all P values < .006). In survivors who received no CRT, dexamethasone was associated with impaired attention (relative risk [RR], 2.12; 95% CI, 1.11 to 4.03) and executive function (RR, 2.42; 95% CI, 1.20 to 4.91). The impact of CRT was dependent on young age at diagnosis for intelligence, academic, and memory functions. Risk for executive function problems increased with survival time in a CRT dose-dependent fashion. In all survivors, self-reported behavior problems increased by 5% (RR, 1.05; 95% CI, 1.01 to 1.09) with each year from diagnosis. Impairment was associated with reduced educational attainment and unemployment.

Conclusion: This study demonstrates persistent and significant neurocognitive impairment in adult survivors of childhood ALL and warrants ongoing monitoring of brain health to facilitate successful adult development and to detect early onset of decline as survivors mature.

Fig 1.

Percentage of survivors with severe impairment across eight domains of neurocognitive function. Rates are presented by treatment exposure (no cranial radiation therapy [CRT], 18-Gy CRT, and 24-Gy CRT) within three groupings of current age (< 30, 30 to 35, and ≥ 36 years old). No data are presented for the no-CRT group at ≥ 36 years of age and the 24-Gy CRT group at age younger than 30 years because of few survivors being in these cells. The dotted line at the bottom of the figure represents the expected level of severe impairment in the general population.

Fig 2.

(A) Relative risk for severe neurocognitive impairment in academic skills and memory by age at diagnosis and dose of cranial radiation therapy (CRT). (B) Relative risk for severe neurocognitive impairment in executive function by time since diagnosis and dose of CRT. For each dose grouping of CRT (18 Gy or 24 Gy), relative risk is calculated in reference to the no-CRT group, which is represented by the solid back horizontal line.