Additional doses of intrathecal therapy may lead to significant reductions in the rate of central nervous system (CNS) relapse in pediatric patients with high-risk acute lymphoblastic leukemia (ALL). Results from the phase 3 St Jude Total Therapy Study 16 clinical trial ( Identifier: NCT00549848) were published in the Journal of Clinical Oncology and described more than a 3-fold reduction in CNS relapse, from 5.7% of patients to 1.8%, the lowest reported CNS relapse rate in high-risk patients of any study to date.

The study enrolled 598 patients between the ages of 0 and 18 years who were treated at St Jude Children’s Hospital from 2007 to 2017. Researchers evaluated interventions to reduce the risk for CNS relapse in patients at high risk.

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The study had 2 main research objectives. Firstly, researchers compared 2 doses of PEG-asparaginase (2500 U/m2 vs 3500 U/m2) to be given on the first day of continuation treatment. They found no significant difference in cumulative risk for CNS relapse or continuous complete remission rate with randomization of these doses.

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The second objective was to determine whether early intensification of triple intrathecal chemotherapy (methotrexate, hydrocortisone, and cytarabine) yielded reduced rates of CNS relapse in patients identified to be at high risk for relapse. The researchers found that 2 additional doses of triple intrathecal chemotherapy during the first 2 weeks of remission induction were associated with reduced risk for CNS relapse in high-risk patients. Of note, this was accompanied by no substantial increase in toxicity.

The rate of overall survival at 5 years was 94.1%, and the rate of event-free survival at 5 years was 88.2%. Cumulative risk for any relapse was 6.6%, with 4.6% risk for isolated hematologic relapse, 1.5% risk for isolated or combined CNS relapse, and a single patient experiencing a single-site testicular relapse.

The researchers presented additional evidence that rates of CNS relapse in pediatric patients with leukemia could be further driven down without substantially increasing toxicity or using prophylactic cranial radiation, which comes with a host of well-described long- and short-term side effects.

The ongoing Total Therapy Study 17 trial ( Identifier: NCT03117751) incorporates immunotherapies such as chimeric antigen receptor T-cells and other targeted therapies and continues to further stratify patients based on their risk for relapse, with the hope of further reducing relapse rates.


1. Jeha S, Pei D, Choi J, et al. Improved CNS control of childhood acute lymphoblastic leukemia without cranial irradiation: St Jude Total Therapy Study 16 [published online October 28, 2019]. J Clin Oncol. doi:10.1200/JCO.19.01692