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J Clin Oncol. 2016 Jul 10;34(20):2380-8. doi: 10.1200/JCO.2015.62.4544. Epub 2016 Apr 25.

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.

Author information

1
Eric C. Larsen, Maine Children's Cancer Program, Scarborough, ME; Meenakshi Devidas and Si Chen, University of Florida, Gainesville, FL; Wanda L. Salzer, US Army Medical Research and Materiel Command, Frederick; Michael J. Borowitz, Johns Hopkins Medical Institutions, Baltimore, MD; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT, Mignon L. Loh, University of California, San Francisco, San Francisco, CA; Leonard A. Mattano Jr, HARP Pharma Consulting, Mystic, CT; Catherine Cole, Princess Margaret Hospital for Children; University of Western Australia, Perth, Western Australia, Australia; Alisa Eicher, Doernbecher Children's Hospital, Portland, OR; Maureen Haugan, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Mark Sorenson, University of Iowa Hospitals and Clinics, Iowa City, IA; Nyla A. Heerema and Julie M. Gastier-Foster, The Ohio State University School of Medicine, Columbus, OH; Andrew A. Carroll, University of Alabama at Birmingham, Birmingham, AL; Brent L. Wood, University of Washington, Seattle, WA; Cheryl L. Willman, University of New Mexico, Albuquerque, NM; Naomi J. Winick, University of Texas Southwestern Medical Center, Dallas, TX; Stephen P. Hunger, Children's Hospital of Philadelphia; University of Pennsylvania, Philadelphia, PA; and William L. Carroll, New York University Medical Center, New York, NY. larsee1@mmc.org.
2
Eric C. Larsen, Maine Children's Cancer Program, Scarborough, ME; Meenakshi Devidas and Si Chen, University of Florida, Gainesville, FL; Wanda L. Salzer, US Army Medical Research and Materiel Command, Frederick; Michael J. Borowitz, Johns Hopkins Medical Institutions, Baltimore, MD; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT, Mignon L. Loh, University of California, San Francisco, San Francisco, CA; Leonard A. Mattano Jr, HARP Pharma Consulting, Mystic, CT; Catherine Cole, Princess Margaret Hospital for Children; University of Western Australia, Perth, Western Australia, Australia; Alisa Eicher, Doernbecher Children's Hospital, Portland, OR; Maureen Haugan, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Mark Sorenson, University of Iowa Hospitals and Clinics, Iowa City, IA; Nyla A. Heerema and Julie M. Gastier-Foster, The Ohio State University School of Medicine, Columbus, OH; Andrew A. Carroll, University of Alabama at Birmingham, Birmingham, AL; Brent L. Wood, University of Washington, Seattle, WA; Cheryl L. Willman, University of New Mexico, Albuquerque, NM; Naomi J. Winick, University of Texas Southwestern Medical Center, Dallas, TX; Stephen P. Hunger, Children's Hospital of Philadelphia; University of Pennsylvania, Philadelphia, PA; and William L. Carroll, New York University Medical Center, New York, NY.

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.

PMID:
27114587
PMCID:
PMC4981974
DOI:
10.1200/JCO.2015.62.4544
[Indexed for MEDLINE]
Free PMC Article

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