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Comparison of Long-Term Neurocognitive Outcomes in Young Children With Acute Lymphoblastic Leukemia Treated With Cranial Radiation or High-Dose or Very High-Dose Intravenous Methotrexate

Brenda J. Spiegler, Kimberly Kennedy, Ronnen Maze, Mark L. Greenberg, Sheila Weitzman, Johann K. Hitzler, Paul C. Nathan

From the Department of Paediatrics, Division of Haematology/Oncology; and the Department of Psychology, The Hospital for Sick Children, The University of Toronto, Toronto, Ontario, Canada

Address reprint requests to Brenda J. Spiegler, PhD, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada; e-mail: brenda.spiegler{at}sickkids.ca

PURPOSE: Cranial radiation therapy (CRT) is associated with neurocognitive morbidity in survivors of childhood acute lymphoblastic leukemia (ALL). For most patients, CRT has been replaced with intensified systemic and intrathecal chemotherapy, often including methotrexate (MTX). The impact of chemotherapy-only protocols on neurocognitive outcomes is unclear, and the importance of systemic MTX dose has not been established.

PATIENTS AND METHODS: Seventy nine of 120 eligible children diagnosed with high-risk ALL between the ages of 1.0 and 4.9 years participated in this retrospective cohort study. All patients were treated on a uniform chemotherapy protocol with one of three modalities of CNS prophylaxis, depending on their treatment era. In addition to intrathecal therapy, CNS-directed therapy consisted of CRT (18 Gy in 10 fractions) in 25 patients, high-dose intravenous (IV) MTX (8 g/m² x 3 doses) in 32 patients and very high-dose IV MTX (33.6 g/m² x 3 doses) in 22 patients. Participants completed tests of intelligence, academic achievement, attention, and memory.

RESULTS: Neurocognitive assessment was conducted at least 5 years after diagnosis (mean, 10.5 years, standard deviation, 2.7 years). No difference was detected on any neurocognitive measure between children treated with high-dose or very high-dose IV MTX. The combined MTX groups scored near the population mean on 17/18 measures. Children treated with CRT performed more poorly than the MTX group on most measures.

CONCLUSION: Treatment strategies for young children with ALL that avoid CRT are associated with good long-term neurocognitive outcomes. In this cohort, the dose of IV MTX did not influence these outcomes.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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Related Correspondence

• Comparison of Long-Term Neurocognitive Outcomes in Young Children With Acute Lymphatic Leukemia Treated With Cranial Radiation or High-Dose or Very High-Dose Intravenous Methotrexate
  Ian J. Cohen
  JCO 2007 25: 734-735 [Full Text]

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