Comparison of Neurocognitive Functioning in Children Previously Randomly Assigned to Intrathecal Methotrexate Compared With Triple Intrathecal Therapy for the Treatment of Childhood Acute Lymphoblastic Leukemia

Abstract

Purpose For the majority of children with acute lymphoblastic leukemia (ALL), CNS prophylaxis consists of either intrathecal (IT) methotrexate or triple IT therapy (ie, methotrexate with both cytarabine and hydrocortisone). The long-term neurotoxicities of these two IT strategies have not yet been directly compared. Patients and Methods In this multisite study, 171 children with standard-risk ALL, age 1 to 9.99 years at diagnosis, previously randomly assigned to IT methotrexate (n = 82) or to triple IT therapy (n = 89) on CCG 1952, underwent neurocognitive evaluation by a licensed psychologist at a mean of 5.9 years after random assignment. Results Patients who received IT methotrexate had a mean Processing Speed Index that was 3.6 points lower, about one fourth of a standard deviation, than those who received triple IT therapy (P = .04) after analysis was adjusted for age, sex, and time since diagnosis. Likewise, 19.5% of children in the IT methotrexate group had a Processing Speed Index score in the below-average range compared with 6.9% in the triple IT therapy group (P = .02). Otherwise, the groups performed similarly on tests of full-scale intelligence quotient, academic achievement, attention/concentration, memory, and visual motor integration. The association of treatment with measures of cognitive functioning was not modified by sex or age at diagnosis. In the post-therapy period, there were no group differences in special education services, neurologic events, or use of psychotropic medications. Conclusion This study did not show any clinically meaningful differences in neurocognitive functioning between patients previously randomly assigned to IT methotrexate or triple IT therapy except for a small difference in processing speed in the IT methotrexate group.

The Behavior Rating Inventory of Executive Function (BRIEF) to Identify Pediatric Acute Lymphoblastic Leukemia (ALL) Survivors At Risk for Neurocognitive Impairment

“…There were no differences between participants and non-participants with respect to age at diagnosis, elapsed time since treatment, or gender. [27, 29] Also see supplementary materials for additional information.…”

Neuromuscular impairments in adult survivors of childhood acute lymphoblastic leukemia

“…1 Contemporary therapy has diminished relapse rates, 2 second malignant neoplasms, 3 and severe neurocognitive outcomes. 4, 5 Nevertheless, current treatment regimens contain chemotherapeutic agents that have the potential to interfere with long-term neuromuscular health and physical function. 6 …”

Mathematics intervention for prevention of neurocognitive deficits in childhood leukemia

“…While the adverse effects of central nervous system (CNS) radiation are well documented, [3–7] intrathecal and systemic methotrexate are also associated with neuroanatomical changes, [8–10] and academic and cognitive problems. [11–16] Recent work also demonstrates systemic methotrexate therapy is associated with impairment in working memory and visual-spatial organization and reasoning. [17] Two meta-analytic reviews confirm the existence of significant neurocognitive sequelae in children treated for leukemia with and without radiation.…”