Cognitive outcomes following contemporary treatment without cranial irradiation for childhood acute lymphoblastic leukemia

Abstract

Background: Treatment of acute lymphoblastic leukemia (ALL) has included the use of prophylactic cranial irradiation in up to 20% of children with high-risk disease despite known cognitive risks of this treatment modality.

Methods: Patients enrolled on the St Jude ALL Total Therapy Study XV, which omitted prophylactic cranial irradiation in all patients, were assessed 120 weeks after completion of consolidation therapy (n = 243) using a comprehensive cognitive battery. χ(2) analysis was used to compare the percentage of below-average performers among the entire ALL patient group to the expected rate based on the normative sample. Univariate logistic regression was used to estimate the effect of intensity of chemotherapy (treatment arm), age at diagnosis, and sex on the probability of below-average performance. All statistical tests were two-sided.

Results: Overall, the ALL group had a statistically significantly higher risk for below-average performance on a measure of sustained attention (67.31% more than 1 SD below the normative mean for omission errors, P < .001) but not on measures of intellectual functioning, academic skills, or memory. Patients given higher intensity chemotherapy were at greater risk for below-average performance compared with those given lower intensity therapy on measures of processing speed (27.14% vs 6.25%, P = .009) and academic abilities (Math Reasoning: 18.60% vs 3.90%, P = .008; Word Reading: 20.00% vs 2.60%, P = .007; Spelling: 27.91% vs 3.90%, P = .001) and had higher parent-reported hyperactivity (23.00% vs 9.84%, P = .018) and learning problems (35.00% vs 16.39%, P = .005). Neither age at diagnosis nor sex was associated with risk for below-average cognitive performance.

Conclusions: Omitting cranial irradiation may help preserve global cognitive abilities, but treatment with chemotherapy alone is not without risks. Caregiver education and development of interventions should address both early attention deficits and cognitive late effects.

Figure 1.

Performance related to treatment risk arm. Black line indicates the expected rate of below-average scores (16%). The asterisk signifies a statistically significant difference in rate of below-average performance between low- and standard/high-risk arms based on univariate logistic regression. All statistical tests were two-sided. WIAT = Wechsler Individual Achievement Test; CPT = Conners’ Continuous Performance Test; CVLT = California Verbal Learning Test; CPRS = Conners’ Parent Rating Scale; FSIQ = Full Scale Intelligence Quotient; FFD= Freedom From Distractibility Index; RT = reaction time; SD = short delay; LD = long delay; Proc Speed = processing speed; Impuls-Hyper = Impulsivity–Hyperactivity Index.

Figure 2.

Performance related to age at diagnosis. Black line indicates the expected rate of below-average scores (16%). All statistical tests were two-sided. WIAT = Wechsler Individual Achievement Test; CPT = Conners’ Continuous Performance Test; CVLT = California Verbal Learning Test; CPRS = Conners’ Parent Rating Scale; FSIQ = Full Scale Intelligence Quotient; FFD = Freedom From Distractibility Index; RT = reaction time; SD = short delay; LD = long delay; Proc Speed = processing speed; Impuls-Hyper = Impulsivity–Hyperactivity Index.

Figure 3.

Performance related to sex. Black line indicates the expected rate of below-average scores (16%). All statistical tests were two-sided. WIAT = Wechsler Individual Achievement Test; CPT = Conners’ Continuous Performance Test; CVLT = California Verbal Learning Test; CPRS = Conners’ Parent Rating Scale; FSIQ = Full Scale Intelligence Quotient; FFD = Freedom From Distractibility Index; RT = reaction time; SD = short delay; LD = long delay; Proc Speed = processing speed; Impuls-Hyper = Impulsivity–Hyperactivity Index.