Prognostic significance of minimal residual disease in high risk B-ALL

A report from Children's Oncology Group study AALL0232

Michael J Borowitz, Brent L. Wood, Meenakshi Devidas, Mignon L. Loh, Elizabeth A. Raetz, Wanda L. Salzer, James B. Nachman, Andrew J. Carroll, Nyla A. Heerema, Julie M. Gastier-Foster, Cheryl L. Willman, Yunfeng Dai, Naomi J. Winick, Stephen P. Hunger, William L. Carroll, Eric Larsen

Research output: Contribution to journalArticle

Abstract

Minimal residual disease (MRD) is highly prognostic in pediatric B-precursor acute lymphoblastic leukemia (B-ALL). In Children's Oncology Group high-risk B-ALL study AALL0232, we investigated MRD in subjects randomized in a 2 x 2 factorial design to receive either high-dose methotrexate (HD-MTX) or Capizzi methotrexate (C-MTX) during interim maintenance (IM) or prednisone or dexamethasone during induction. Subjects with end-induction MRD ≥0.1% or those with morphologic slow early response were nonrandomly assigned to receive a second IM and delayed intensification phase. MRD was measured by 6-color flow cytometry in 1 of 2 reference labs, with excellent agreement between the two. Subjects with end-induction MRD 0.1% did not improve either 5-year EFS or overall survival (OS). However, these subjects showed an early relapse rate similar to that seen in MRD-negative ones, with EFS/OS curves for patients with 0.1% to 1% MRD crossing those with 0.01% to 0.1% MRD at 3 and 4 years, thus suggesting that the intensified therapy altered the disease course of MRD-positive subjects. Additional interventions targeted at the MRD-positive group may further improve outcome. This trial was registered at www.clinicaltrials.gov as #NCT00075725.

Original languageEnglish (US)
Pages (from-to)964-971
Number of pages8
JournalBlood
Volume126
Issue number8
DOIs
StatePublished - Aug 20 2015

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Oncology
Residual Neoplasm
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Methotrexate
Maintenance
Survival
Pediatrics
Flow cytometry
Prednisone
Dexamethasone
Flow Cytometry
Color
Recurrence

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Prognostic significance of minimal residual disease in high risk B-ALL : A report from Children's Oncology Group study AALL0232. / Borowitz, Michael J; Wood, Brent L.; Devidas, Meenakshi; Loh, Mignon L.; Raetz, Elizabeth A.; Salzer, Wanda L.; Nachman, James B.; Carroll, Andrew J.; Heerema, Nyla A.; Gastier-Foster, Julie M.; Willman, Cheryl L.; Dai, Yunfeng; Winick, Naomi J.; Hunger, Stephen P.; Carroll, William L.; Larsen, Eric.

In: Blood, Vol. 126, No. 8, 20.08.2015, p. 964-971.

Research output: Contribution to journalArticle

Borowitz, MJ, Wood, BL, Devidas, M, Loh, ML, Raetz, EA, Salzer, WL, Nachman, JB, Carroll, AJ, Heerema, NA, Gastier-Foster, JM, Willman, CL, Dai, Y, Winick, NJ, Hunger, SP, Carroll, WL & Larsen, E 2015, 'Prognostic significance of minimal residual disease in high risk B-ALL: A report from Children's Oncology Group study AALL0232', Blood, vol. 126, no. 8, pp. 964-971. https://doi.org/10.1182/blood-2015-03-633685
Borowitz, Michael J ; Wood, Brent L. ; Devidas, Meenakshi ; Loh, Mignon L. ; Raetz, Elizabeth A. ; Salzer, Wanda L. ; Nachman, James B. ; Carroll, Andrew J. ; Heerema, Nyla A. ; Gastier-Foster, Julie M. ; Willman, Cheryl L. ; Dai, Yunfeng ; Winick, Naomi J. ; Hunger, Stephen P. ; Carroll, William L. ; Larsen, Eric. / Prognostic significance of minimal residual disease in high risk B-ALL : A report from Children's Oncology Group study AALL0232. In: Blood. 2015 ; Vol. 126, No. 8. pp. 964-971.
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abstract = "Minimal residual disease (MRD) is highly prognostic in pediatric B-precursor acute lymphoblastic leukemia (B-ALL). In Children's Oncology Group high-risk B-ALL study AALL0232, we investigated MRD in subjects randomized in a 2 x 2 factorial design to receive either high-dose methotrexate (HD-MTX) or Capizzi methotrexate (C-MTX) during interim maintenance (IM) or prednisone or dexamethasone during induction. Subjects with end-induction MRD ≥0.1{\%} or those with morphologic slow early response were nonrandomly assigned to receive a second IM and delayed intensification phase. MRD was measured by 6-color flow cytometry in 1 of 2 reference labs, with excellent agreement between the two. Subjects with end-induction MRD 0.1{\%} did not improve either 5-year EFS or overall survival (OS). However, these subjects showed an early relapse rate similar to that seen in MRD-negative ones, with EFS/OS curves for patients with 0.1{\%} to 1{\%} MRD crossing those with 0.01{\%} to 0.1{\%} MRD at 3 and 4 years, thus suggesting that the intensified therapy altered the disease course of MRD-positive subjects. Additional interventions targeted at the MRD-positive group may further improve outcome. This trial was registered at www.clinicaltrials.gov as #NCT00075725.",
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AU - Loh, Mignon L.

AU - Raetz, Elizabeth A.

AU - Salzer, Wanda L.

AU - Nachman, James B.

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AU - Willman, Cheryl L.

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