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Blood, 15 June 2008, Vol. 111, No. 12, pp. 5477-5485.
Prepublished online as a Blood First Edition Paper on April 3, 2008; DOI 10.1182/blood-2008-01-132837.
 Previous Article | Next Article 
Submitted January 18, 2008
Accepted March 9, 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
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, and Bruce M Camitta
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, United States
Children's Oncology Group and the College of Medicine, University of Florida, Gainesville, FL, United States
Heath Science Center, University of Colorado Denver and The Children's Hospital, Aurora, CO, United States
Cook Children's Hospital, Fort Worth, TX, United States
University of Alabama, Birmingham, Birmingham, AL, United States
New York University School of Medicine, New York, NY, United States
Duke University School of Medicine, Durham, NC, United States
University of Mississippi School of Medicine, Jackson, MI, United States
Mayo Clinic, Rochester, MN, United States
University of New Mexico School of Medicine, Albuquerque, NM, United States
University of Texas Southwestern School of Medicine, Dallas, TX, United States
Midwest Children's Cancer Center, Medical College of Wisconsin, Milwaukee, WS, United States
* Corresponding author; email: mborowit{at}jhmi.edu.
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-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 0.01-0.1% day 29 MRD had poor outcome compared to MRD negative patients (59±5% vs 88±1% 5 y EFS). Presence of good prognostic markers TEL-AML1 or trisomies of chromosomes 4 and 10 still provided additional prognostic information, but not in NCI HR patients who were MRD positive. The few patients with detectable MRD at end consolidation fared especially poorly with only a 43±7% 5 y EFS. D29 marrow MRD was the most important prognostic variable in multivariate 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±1% 5 y EFS with non-intensive therapy. These studies are registered at www.ClinicalTrials.gov as NCT00005585, NCT00005596, and NCT00005603.
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