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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: 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.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.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.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.

SUBMITTER: Kadan-Lottick NS

PROVIDER: S-EPMC2793042 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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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.

Kadan-Lottick Nina S NS Brouwers Pim P Breiger David D Kaleita Thomas T Dziura James J Northrup Veronika V Chen Lu L Nicoletti Megan M Bostrom Bruce B Stork Linda L Neglia Joseph P JP

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20091102 35

<h4>Purpose</h4>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.<h4>Patients and methods</h4>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 ...[more]

PMID: 19884541

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Project description:ObjectiveChildren with acute lymphoblastic leukemia (ALL) are at risk for neurocognitive deficits, and examining individual variability is essential to understand these risks. This study evaluated latent longitudinal trajectories and risk factors of neurocognitive outcomes in childhood ALL.MethodsThere were 233 participants with ALL who were enrolled on a phase 3, risk-stratified chemotherapy-only clinical trial (NCT00137111) and who completed protocol-directed neurocognitive assessments [47.6% female, mean (SD) = 6.6 (3.7) years]. Measures of sustained attention, learning/memory, and parent ratings of attention were completed during and after treatment. Longitudinal latent class analyses were used to classify participants into distinct trajectories. Logistic regression was used to identify predictors of class membership.ResultsWithin the overall group, attention performance was below age expectations across time (Conners Continuous Performance Test detectability/variability, p < 0.01); memory performance and parent ratings were below expectations at later phases (California Verbal Learning Test learning slope, p < 0.05; Conners Parent Rating Scale, Revised attention/learning, p < 0.05). Most participants (80-89%) had stable neurocognitive profiles; smaller groups showed declining (3-6%) or improving (3-11%) trajectories. Older age (p = 0.020), female sex (p = 0.018), and experiencing sepsis (p = 0.047) were associated with greater attention problems over time. Lower baseline IQ was associated with improved memory (p = 0.035) and fewer ratings of attention problems (p = 0.013) over time.ConclusionsMost patients with ALL have stable neurocognitive profiles. Smaller groups have significant impairments shortly after diagnosis or have worsening performance over time. A tiered assessment approach, which includes consideration of individual and clinical risk factors, may be useful for monitoring neurocognitive functioning during treatment and survivorship.

Dataset Information

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.

Publications

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.

Similar Datasets

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