Benefit of Dexamethasone and High-Dose Methotrexate in Children/Young Adults With High-Risk B-Acute Lymphoblastic Leukemia


Key Points

  • Mature results indicate superiority of high-dose vs Capizzi methotrexate.
  • Dexamethasone during induction was associated with benefit in children aged 1 to 9 years, but not in older patients.

As reported by Larsen et al in the Journal of Clinical Oncology, final data from the Children’s Oncology Group (COG) AALL0232 trial indicate that the event-free survival benefit of high-dose methotrexate was maintained in children/young adults with high-risk B-acute lymphoblastic leukemia. Dexamethasone in combination with high-dose methotrexate was of benefit in younger children.

Study Details

In the trial, 2,914 patients aged 1 to 30 years were randomized in 2:3:2 factorial fashion between January 2004 and January 2011 to receive dexamethasone (14 days) vs prednisone (28 days) during induction, and high-dose methotrexate vs Capizzi escalating-dose methotrexate plus pegaspargase (Oncaspar) during interim maintenance 1.

Interim and Final Results

Interim analysis showed superiority of high-dose methotrexate regimens, leading to cessation of enrollment in January 2011. At that time, 5-year event-free survival was 82% among patients receiving high-dose methotrexate during interim maintenance 1 vs 75.4% among those receiving Capizzi methotrexate (P = .006).

Mature final data showed 5-year event-free survival rates of 79.6% for high-dose vs 75.2% for Capizzi methotrexate (P = .008), with high-dose methotrexate being associated with decreased marrow and central nervous system recurrences.

Patients aged 1 to 9 years who received dexamethasone and high-dose methotrexate had better 5-year event-free survival vs those receiving other regimens (91.2% vs 83.2% for dexamethasone plus Capizzi methotrexate, 80.8% for prednisone plus high-dose methotrexate, and 82.1% for prednisone plus Capizzi methotrexate; P = .015). No benefit of dexamethasone during induction was observed in older patients, who had excess rates of osteonecrosis.

The investigators concluded, “High-dose methotrexate is superior to Capizzi methotrexate for the treatment of high-risk B-acute lymphoblastic leukemia, with no increase in acute toxicity. Dexamethasone given during induction benefited younger children but provided no benefit and was associated with a higher risk of osteonecrosis among participants 10 years and older.”

The study was supported by the Children’s Oncology Group and National Cancer Institute.

Eric C. Larsen, MD, of Maine Children’s Cancer Program, Scarborough, is the corresponding author for the Journal of Clinical Oncology article. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.