Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors

A Children's Oncology Group study

Michael J Borowitz, Meenakshi Devidas, Stephen P. Hunger, W. Paul Bowman, Andrew J. Carroll, William L. Carroll, Stephen Linda, Paul L. Martin, D. Jeanette Pullen, David Viswanatha, Cheryl L. Willman, Naomi Winick, Bruce M. Camitta

Research output: Contribution to journalArticle

Abstract

Minimal residual disease (MRD) is an important predictor of relapse in acute lymphoblastic leukemia (ALL), but its relationship to other prognostic variables has not been fully assessed. The Children's Oncology Group studied the prognostic impact of MRD measured by flow cytometry in the peripheral blood at day 8, and in end-induction (day 29) and end-consolidation marrows in 2143 children with precursor B-cell ALL (B-ALL). The presence of MRD in day-8 blood and day-29 marrow MRD was associated with shorter event-free survival (EFS) in all risk groups; even patients with 0.01% to 0.1 % day-29 MRD had poor outcome compared with patients negative for MRD patients (59% ± 5% vs 88% ± 1% 5-year EFS). Presence of good prognostic markers TEL-AML1 or trisomies of chromosomes 4 and 10 still provided additional prognostic information, but not in National Cancer Insitute high-risk (NCI HR) patients who were MRD +. The few patients with detectable MRD at end of consolidation fared especially poorly, with only a 43% plus or minus 7% 5-year EFS. Day-29 marrow MRD was the most important prognostic variable in multi-variate analysis. The 12% of patients with all favorable risk factors, including NCI risk group, genetics, and absence of days 8 and 29 MRD, had a 97% plus or minus 1% 5-year EFS with nonintensive therapy. These studies are registered at www.clinicaltrials.gov as NCT00005585, NCT00005596, and NCT00005603.

Original languageEnglish (US)
Pages (from-to)5477-5485
Number of pages9
JournalBlood
Volume111
Issue number12
DOIs
StatePublished - Jun 15 2008

Fingerprint

Oncology
Residual Neoplasm
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Disease-Free Survival
Bone Marrow
Consolidation
Blood
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
Chromosomes, Human, Pair 10
Chromosomes, Human, Pair 4
Flow cytometry
Trisomy
Chromosomes
Flow Cytometry
Cells
Recurrence

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors : A Children's Oncology Group study. / Borowitz, Michael J; Devidas, Meenakshi; Hunger, Stephen P.; Bowman, W. Paul; Carroll, Andrew J.; Carroll, William L.; Linda, Stephen; Martin, Paul L.; Pullen, D. Jeanette; Viswanatha, David; Willman, Cheryl L.; Winick, Naomi; Camitta, Bruce M.

In: Blood, Vol. 111, No. 12, 15.06.2008, p. 5477-5485.

Research output: Contribution to journalArticle

Borowitz, MJ, Devidas, M, Hunger, SP, Bowman, WP, Carroll, AJ, Carroll, WL, Linda, S, Martin, PL, Pullen, DJ, Viswanatha, D, Willman, CL, Winick, N & Camitta, BM 2008, 'Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: A Children's Oncology Group study', Blood, vol. 111, no. 12, pp. 5477-5485. https://doi.org/10.1182/blood-2008-01-132837
Borowitz, Michael J ; Devidas, Meenakshi ; Hunger, Stephen P. ; Bowman, W. Paul ; Carroll, Andrew J. ; Carroll, William L. ; Linda, Stephen ; Martin, Paul L. ; Pullen, D. Jeanette ; Viswanatha, David ; Willman, Cheryl L. ; Winick, Naomi ; Camitta, Bruce M. / Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors : A Children's Oncology Group study. In: Blood. 2008 ; Vol. 111, No. 12. pp. 5477-5485.
@article{aaaf92fc08d14bbe9922e6fe3dffc9d9,
title = "Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: A Children's Oncology Group study",
abstract = "Minimal residual disease (MRD) is an important predictor of relapse in acute lymphoblastic leukemia (ALL), but its relationship to other prognostic variables has not been fully assessed. The Children's Oncology Group studied the prognostic impact of MRD measured by flow cytometry in the peripheral blood at day 8, and in end-induction (day 29) and end-consolidation marrows in 2143 children with precursor B-cell ALL (B-ALL). The presence of MRD in day-8 blood and day-29 marrow MRD was associated with shorter event-free survival (EFS) in all risk groups; even patients with 0.01{\%} to 0.1 {\%} day-29 MRD had poor outcome compared with patients negative for MRD patients (59{\%} ± 5{\%} vs 88{\%} ± 1{\%} 5-year EFS). Presence of good prognostic markers TEL-AML1 or trisomies of chromosomes 4 and 10 still provided additional prognostic information, but not in National Cancer Insitute high-risk (NCI HR) patients who were MRD +. The few patients with detectable MRD at end of consolidation fared especially poorly, with only a 43{\%} plus or minus 7{\%} 5-year EFS. Day-29 marrow MRD was the most important prognostic variable in multi-variate analysis. The 12{\%} of patients with all favorable risk factors, including NCI risk group, genetics, and absence of days 8 and 29 MRD, had a 97{\%} plus or minus 1{\%} 5-year EFS with nonintensive therapy. These studies are registered at www.clinicaltrials.gov as NCT00005585, NCT00005596, and NCT00005603.",
author = "Borowitz, {Michael J} and Meenakshi Devidas and Hunger, {Stephen P.} and Bowman, {W. Paul} and Carroll, {Andrew J.} and Carroll, {William L.} and Stephen Linda and Martin, {Paul L.} and Pullen, {D. Jeanette} and David Viswanatha and Willman, {Cheryl L.} and Naomi Winick and Camitta, {Bruce M.}",
year = "2008",
month = "6",
day = "15",
doi = "10.1182/blood-2008-01-132837",
language = "English (US)",
volume = "111",
pages = "5477--5485",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "12",

}

TY - JOUR

T1 - Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors

T2 - A Children's Oncology Group study

AU - Borowitz, Michael J

AU - Devidas, Meenakshi

AU - Hunger, Stephen P.

AU - Bowman, W. Paul

AU - Carroll, Andrew J.

AU - Carroll, William L.

AU - Linda, Stephen

AU - Martin, Paul L.

AU - Pullen, D. Jeanette

AU - Viswanatha, David

AU - Willman, Cheryl L.

AU - Winick, Naomi

AU - Camitta, Bruce M.

PY - 2008/6/15

Y1 - 2008/6/15

N2 - Minimal residual disease (MRD) is an important predictor of relapse in acute lymphoblastic leukemia (ALL), but its relationship to other prognostic variables has not been fully assessed. The Children's Oncology Group studied the prognostic impact of MRD measured by flow cytometry in the peripheral blood at day 8, and in end-induction (day 29) and end-consolidation marrows in 2143 children with precursor B-cell ALL (B-ALL). The presence of MRD in day-8 blood and day-29 marrow MRD was associated with shorter event-free survival (EFS) in all risk groups; even patients with 0.01% to 0.1 % day-29 MRD had poor outcome compared with patients negative for MRD patients (59% ± 5% vs 88% ± 1% 5-year EFS). Presence of good prognostic markers TEL-AML1 or trisomies of chromosomes 4 and 10 still provided additional prognostic information, but not in National Cancer Insitute high-risk (NCI HR) patients who were MRD +. The few patients with detectable MRD at end of consolidation fared especially poorly, with only a 43% plus or minus 7% 5-year EFS. Day-29 marrow MRD was the most important prognostic variable in multi-variate analysis. The 12% of patients with all favorable risk factors, including NCI risk group, genetics, and absence of days 8 and 29 MRD, had a 97% plus or minus 1% 5-year EFS with nonintensive therapy. These studies are registered at www.clinicaltrials.gov as NCT00005585, NCT00005596, and NCT00005603.

AB - Minimal residual disease (MRD) is an important predictor of relapse in acute lymphoblastic leukemia (ALL), but its relationship to other prognostic variables has not been fully assessed. The Children's Oncology Group studied the prognostic impact of MRD measured by flow cytometry in the peripheral blood at day 8, and in end-induction (day 29) and end-consolidation marrows in 2143 children with precursor B-cell ALL (B-ALL). The presence of MRD in day-8 blood and day-29 marrow MRD was associated with shorter event-free survival (EFS) in all risk groups; even patients with 0.01% to 0.1 % day-29 MRD had poor outcome compared with patients negative for MRD patients (59% ± 5% vs 88% ± 1% 5-year EFS). Presence of good prognostic markers TEL-AML1 or trisomies of chromosomes 4 and 10 still provided additional prognostic information, but not in National Cancer Insitute high-risk (NCI HR) patients who were MRD +. The few patients with detectable MRD at end of consolidation fared especially poorly, with only a 43% plus or minus 7% 5-year EFS. Day-29 marrow MRD was the most important prognostic variable in multi-variate analysis. The 12% of patients with all favorable risk factors, including NCI risk group, genetics, and absence of days 8 and 29 MRD, had a 97% plus or minus 1% 5-year EFS with nonintensive therapy. These studies are registered at www.clinicaltrials.gov as NCT00005585, NCT00005596, and NCT00005603.

UR - http://www.scopus.com/inward/record.url?scp=47049093795&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=47049093795&partnerID=8YFLogxK

U2 - 10.1182/blood-2008-01-132837

DO - 10.1182/blood-2008-01-132837

M3 - Article

VL - 111

SP - 5477

EP - 5485

JO - Blood

JF - Blood

SN - 0006-4971

IS - 12

ER -