A comparison of neurocognitive functioning in children previously randomized to dexamethasone or prednisone in the treatment of childhood acute lymphoblastic leukemia

Abstract

In previous clinical trials of childhood acute lymphoblastic leukemia (ALL), dexamethasone resulted in higher event-free survival rates than prednisone, presumably due to greater central nervous system penetration. Dexamethasone's association with long-term neurocognitive toxicity is unknown. In this multisite study, we measured neurocognitive functioning in 92 children with standard-risk ALL, 1 to 9.99 years at diagnosis, at a mean of 9.8 years after randomization to prednisone (n = 41) or dexamethasone (n = 51) on Children's Cancer Group (CCG) 1922. No significant overall differences in mean neurocognitive and academic performance scores were found between the prednisone and dexamethasone groups after adjusting for age, sex, and time since diagnosis. The exception was that patients receiving dexamethasone scored one-third of a standard deviation worse on word reading (98.8 +/- 1.7 vs 104.9 +/- 1.8; P = .02). There were no group differences in the distribution of test scores or the parents' report of neurologic complications, psychotropic drug use, and special education. Further analyses suggested for the dexamethasone group, older age of diagnosis was associated with worse neurocognitive functioning; for the prednisone group, younger age at diagnosis was associated with worse functioning. In conclusion, our study did not demonstrate any meaningful differences in long-term cognitive functioning of childhood ALL patients based on corticosteroid randomization. This study is registered with http://www.clinicaltrials.gov under NCT00085176.

Figure 1

Sex-specific differences in processing speed between dexamethasone and prednisone. Interactions for other neurocognitive outcomes are not displayed because they were not significant at P < .05. Data are presented as least squares means (SE) from multiple linear regression adjusted for age at diagnosis and time elapsed since diagnosis. The P value for interaction represents the test of whether the magnitude of group differences was dependent on sex. Bracketed P values represent sex-specific comparisons between dexamethasone and prednisone.

Figure 2

Age at diagnosis-specific differences in neurocognitive outcomes between dexamethasone and prednisone. Only neurocognitive outcomes for which the interaction is significant (P < .05) are displayed: (A) WISC-IV full scale IQ, (B) WISC-IV processing speed index, (C) WIAT II-A spelling, (D) WIAT II-A word reading. Data are presented as least squares means (SE) from multiple linear regression adjusted for sex and time elapsed since diagnosis. The P values for interactions refer to tests of whether the magnitude of group differences was dependent on age at diagnosis. Bracketed P values represent age-specific comparisons between dexamethasone and prednisone.