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

Eric C. Larsen, Meenakshi Devidas, Si Chen, Wanda L. Salzer, Elizabeth A. Raetz, Mignon L. Loh, Leonard A. Mattano, 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

Research output: Contribution to journalArticle

86 Citations (Scopus)

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). Highdose 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.

Original languageEnglish (US)
Pages (from-to)2380-2388
Number of pages9
JournalJournal of Clinical Oncology
Volume34
Issue number20
DOIs
StatePublished - Jul 10 2016

Fingerprint

Precursor Cell Lymphoblastic Leukemia-Lymphoma
Methotrexate
Dexamethasone
Young Adult
Disease-Free Survival
Osteonecrosis
Maintenance
Survival
Prednisone
Survival Rate
Bone Marrow
Recurrence

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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. / Larsen, Eric C.; Devidas, Meenakshi; Chen, Si; Salzer, Wanda L.; Raetz, Elizabeth A.; Loh, Mignon L.; Mattano, Leonard A.; Cole, Catherine; Eicher, Alisa; Haugan, Maureen; Sorenson, Mark; Heerema, Nyla A.; Carroll, Andrew A.; Gastier-Foster, Julie M.; Borowitz, Michael J.; Wood, Brent L.; Willman, Cheryl L.; Winick, Naomi J.; Hunger, Stephen P.; Carroll, William L.

In: Journal of Clinical Oncology, Vol. 34, No. 20, 10.07.2016, p. 2380-2388.

Research output: Contribution to journalArticle

Larsen, EC, Devidas, M, Chen, S, Salzer, WL, Raetz, EA, Loh, ML, Mattano, LA, Cole, C, Eicher, A, Haugan, M, Sorenson, M, Heerema, NA, Carroll, AA, Gastier-Foster, JM, Borowitz, MJ, Wood, BL, Willman, CL, Winick, NJ, Hunger, SP & Carroll, WL 2016, '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', Journal of Clinical Oncology, vol. 34, no. 20, pp. 2380-2388. https://doi.org/10.1200/JCO.2015.62.4544
Larsen, Eric C. ; Devidas, Meenakshi ; Chen, Si ; Salzer, Wanda L. ; Raetz, Elizabeth A. ; Loh, Mignon L. ; Mattano, Leonard A. ; Cole, Catherine ; Eicher, Alisa ; Haugan, Maureen ; Sorenson, Mark ; Heerema, Nyla A. ; Carroll, Andrew A. ; Gastier-Foster, Julie M. ; Borowitz, Michael J. ; Wood, Brent L. ; Willman, Cheryl L. ; Winick, Naomi J. ; Hunger, Stephen P. ; Carroll, William L. / 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. In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 20. pp. 2380-2388.
@article{166276a2cd054260a9f2b618215346ce,
title = "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). Highdose 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.",
author = "Larsen, {Eric C.} and Meenakshi Devidas and Si Chen and Salzer, {Wanda L.} and Raetz, {Elizabeth A.} and Loh, {Mignon L.} and Mattano, {Leonard A.} and Catherine Cole and Alisa Eicher and Maureen Haugan and Mark Sorenson and Heerema, {Nyla A.} and Carroll, {Andrew A.} and Gastier-Foster, {Julie M.} and Borowitz, {Michael J.} and Wood, {Brent L.} and Willman, {Cheryl L.} and Winick, {Naomi J.} and Hunger, {Stephen P.} and Carroll, {William L.}",
year = "2016",
month = "7",
day = "10",
doi = "10.1200/JCO.2015.62.4544",
language = "English (US)",
volume = "34",
pages = "2380--2388",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "20",

}

TY - JOUR

T1 - Dexamethasone and high-dose methotrexate improve outcome for children and young adults with high-risk B-acute lymphoblastic leukemia

T2 - A report from children's oncology group study AALL0232

AU - Larsen, Eric C.

AU - Devidas, Meenakshi

AU - Chen, Si

AU - Salzer, Wanda L.

AU - Raetz, Elizabeth A.

AU - Loh, Mignon L.

AU - Mattano, Leonard A.

AU - Cole, Catherine

AU - Eicher, Alisa

AU - Haugan, Maureen

AU - Sorenson, Mark

AU - Heerema, Nyla A.

AU - Carroll, Andrew A.

AU - Gastier-Foster, Julie M.

AU - Borowitz, Michael J.

AU - Wood, Brent L.

AU - Willman, Cheryl L.

AU - Winick, Naomi J.

AU - Hunger, Stephen P.

AU - Carroll, William L.

PY - 2016/7/10

Y1 - 2016/7/10

N2 - 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). Highdose 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.

AB - 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). Highdose 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.

UR - http://www.scopus.com/inward/record.url?scp=84977505620&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84977505620&partnerID=8YFLogxK

U2 - 10.1200/JCO.2015.62.4544

DO - 10.1200/JCO.2015.62.4544

M3 - Article

VL - 34

SP - 2380

EP - 2388

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 20

ER -