Dexamethasone and High-Dose Methotrexate Improve Outcome for Children and Young Adults With High-Risk B-Acute Lymphoblastic Leukemia: A Report From Children's Oncology Group Study AALL0232.

Abstract

PURPOSE:

Survival for children and young adults with high-risk B-acute lymphoblastic leukemia has improved significantly, but 20% to 25% of patients are not cured. Children's Oncology Group study AALL0232 tested two interventions to improve survival.

PATIENTS AND METHODS:

Between January 2004 and January 2011, AALL0232 enrolled 3,154 participants 1 to 30 years old with newly diagnosed high-risk B-acute lymphoblastic leukemia. By using a 2 × 2 factorial design, 2,914 participants were randomly assigned to receive dexamethasone (14 days) versus prednisone (28 days) during induction and high-dose methotrexate versus Capizzi escalating-dose methotrexate plus pegaspargase during interim maintenance 1.

RESULTS:

Planned interim monitoring showed the superiority of the high-dose methotrexate regimens, which exceeded the predefined boundary and led to cessation of enrollment in January 2011. At that time, participants randomly assigned to high-dose methotrexate during interim maintenance 1 versus those randomly assigned to Capizzi methotrexate had a 5-year event-free survival (EFS) of 82% versus 75.4% (P = .006). Mature final data showed 5-year EFS rates of 79.6% for high-dose methotrexate and 75.2% for Capizzi methotrexate (P = .008). High-dose methotrexate decreased both marrow and CNS recurrences. Patients 1 to 9 years old who received dexamethasone and high-dose methotrexate had a superior outcome compared with those who received the other three regimens (5-year EFS, 91.2% v 83.2%, 80.8%, and 82.1%; P = .015). Older participants derived no benefit from dexamethasone during induction and experienced excess rates of osteonecrosis.

CONCLUSION:

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.

• Authors: Eric C Larsen, Meenakshi Devidas, Si Chen, Wanda L Salzer, Elizabeth A Raetz, Mignon L Loh, Leonard A Mattano Jr, Catherine Cole, Alisa Eicher, Maureen Haugan, Mark Sorenson, Nyla A Heerema, Andrew A Carroll, Julie M Gastier-Foster, Michael J Borowitz, Brent L Wood, Cheryl L Willman, Naomi J Winick, Stephen P Hunger, William L Carroll
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 34 Issue 20 Pg. 2380-8 (07 10 2016) ISSN: 1527-7755 [Electronic] United States
• PMID: 27114587 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
• Copyright: © 2016 by American Society of Clinical Oncology.

Chemical References

• Dexamethasone
• Methotrexate

Topics

• Adult
• Child
• Child, Preschool
• Dexamethasone (administration & dosage, adverse effects)
• Female
• Humans
• Infant
• Male
• Methotrexate (administration & dosage, adverse effects)
• Precursor B-Cell Lymphoblastic Leukemia-Lymphoma (drug therapy, mortality)
• Young Adult