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 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.
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA. mborowit@jhmi.edu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Borowitz
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Devidas
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Hunger
authors.forename: W Paul
authors.initials: WP
authors.lastname: Bowman
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Carroll
authors.forename: William L
authors.initials: WL
authors.lastname: Carroll
authors.forename: Stephen
authors.initials: S
authors.lastname: Linda
authors.forename: Paul L
authors.initials: PL
authors.lastname: Martin
authors.forename: D Jeanette
authors.initials: DJ
authors.lastname: Pullen
authors.forename: David
authors.initials: D
authors.lastname: Viswanatha
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Willman
authors.forename: Naomi
authors.initials: N
authors.lastname: Winick
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Camitta
mesh_terms: D014408:Biomarkers, Tumor; D001853:Bone Marrow / Q000473:pathology; D002648:Child; D002986:Clinical Trials as Topic; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D018572:Disease-Free Survival; D006801:Humans; D015999:Multivariate Analysis; D018365:Neoplasm, Residual / Q000235:genetics / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D011379:Prognosis; D016016:Proportional Hazards Models; D012008:Recurrence; D012307:Risk Factors; D016896:Treatment Outcome; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D014408:Biomarkers, Tumor; D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein