Faculty Collaboration Database

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 2008 Jun 15;111(12):5477-85

Date

04/05/2008

Pubmed ID

18388178

Pubmed Central ID

PMC2424148

DOI

10.1182/blood-2008-01-132837

Scopus ID

2-s2.0-47049093795 (requires institutional sign-in at Scopus site)   665 Citations

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 Institute 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 List

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, Children's Oncology Group

MESH terms used to index this publication - Major topics in bold

Biomarkers, Tumor
Bone Marrow
Child
Clinical Trials as Topic
Core Binding Factor Alpha 2 Subunit
Disease-Free Survival
Humans
Multivariate Analysis
Neoplasm, Residual
Oncogene Proteins, Fusion
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Prognosis
Proportional Hazards Models
Recurrence
Risk Factors
Treatment Outcome