Neurocognitive Functioning of Children Treated for High-Risk B-Acute Lymphoblastic Leukemia Randomly Assigned to Different Methotrexate and Corticosteroid Treatment Strategies: A Report from the Children's Oncology Group

Neurocognitive Functioning of Children Treated for High-Risk B-Acute Lymphoblastic Leukemia Randomly Assigned to Different Methotrexate and Corticosteroid Treatment Strategies: A Report from the Children's Oncology Group
Survivors of childhood ALL are at increased risk for a number of late effects due to treatment, individual and environmental factors, including neurocognitive deficits. This study examined whether there was a difference in neurocognitive outcomes based on the treatment administered during a COG protocol for high-risk B-ALL, with the goal of being able to identify those at increased risk to facilitate earlier intervention. Specifically, this study examined the effect of steroid choice and dosage and method of methotrexate administration on intellectual functioning, working memory and processing speed via a randomized control trial.
192 children who had been enrolled on the COG protocol AALL0232 were examined for IQ, working memory and processing speed 8-24 months after the completion of their HR B-ALL therapy. The children had been randomly assigned, during the initial AALL0232 protocol, to receive either prednisone or dexamethasone (during induction), and to receive either four courses of high dose methotrexate with leucovorin rescue or five doses of escalating dose methotrexate (Capizzi) with PEG asparaginase (during interim maintenance).
After controlling for age, gender, race, ethnicity, time since diagnosis and type of medical insurance, there was no significant difference in IQ, working memory or processing speed found 8-24 months post completion of therapy comparing the different treatment groups. However, both, age and type of medical insurance were found to be significant predictors of decreased IQ (P 0.001), age was also found to be associated with decreased processing speed (P = 0.02) and insurance type (public health insurance rather than private or military insurance) with decreased working memory (P 0.001).
Limitations of this study included its small size, as less than 20% of eligible subjects participated, and the generally younger age and less ethnic diversity of patients captured in this trial. The cross-sectional design is also a limitation, as it would be more useful to measure neurocognitive function longitudinally over time. Finally, there are limitations inherent in the tests used to estimate neurocognitive function.
No association between increased neurocognitive late effects and choice of steroid and type of methotrexate administration was found in children who received treatment for high-risk B-ALL; however, there was an increased risk of neurocognitive dysfunction in younger children, and those from a lower socioeconomic status (estimated by type of medical insurance coverage), who might benefit from earlier neurocognitive interventions.