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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.
Afiliação
  • Borowitz MJ; Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD;
  • Wood BL; Department of Laboratory Medicine, University of Washington, Seattle, WA;
  • Devidas M; Department of Biostatistics, Colleges of Medicine and Public Health & Health Professions, University of Florida, Gainesville, FL;
  • Loh ML; Benioff Children's Hospital and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA;
  • Raetz EA; Department of Pediatrics, University of Utah, Salt Lake City, UT;
  • Salzer WL; US Army Medical Research and Materiel Command, Fort Detrick, MD;
  • Nachman JB; Department of Pediatrics, University of Chicago, Chicago, IL;
  • Carroll AJ; Department of Genetics, University of Alabama at Birmingham, Birmingham, AL;
  • Heerema NA; Department of Pathology, The Ohio State University School of Medicine, Columbus, OH;
  • Gastier-Foster JM; Nationwide Children's Hospital, Columbus, OH;
  • Willman CL; Cancer Center and Departments of Internal Medicine and Pathology, University of New Mexico, Albuquerque, NM;
  • Dai Y; Department of Biostatistics, Colleges of Medicine and Public Health & Health Professions, University of Florida, Gainesville, FL;
  • Winick NJ; University of Texas Southwestern Medical Center, Dallas, TX;
  • Hunger SP; Department of Pediatrics and the Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA;
  • Carroll WL; Department of Pediatrics and The New York University Cancer Institute, New York University Medical Center, New York, NY; and.
  • Larsen E; Maine Children's Cancer Program, Scarborough, ME.
Blood ; 126(8): 964-71, 2015 Aug 20.
Article em En | MEDLINE | ID: mdl-26124497
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 × 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 <0.01% had a 5-year event-free survival (EFS) of 87% ± 1% vs 74% ± 4% for those with MRD 0.01% to 0.1%; increasing MRD amounts was associated with progressively worse outcome. Subjects converting from MRD positive to negative by end consolidation had a relatively favorable 79% ± 5% 5-year disease-free survival vs 39% ± 7% for those with MRD ≥0.01%. Although HD-MTX was superior to C-MTX, MRD retained prognostic significance in both groups (86% ± 2% vs 58% ± 4% for MRD-negative vs positive C-MTX subjects; 88% ± 2% vs 68% ± 4% for HD-MTX subjects). Intensified therapy given to subjects with 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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leucemia-Linfoma Linfoblástico de Células Precursoras B / Neoplasia Residual / Antineoplásicos Tipo de estudo: Clinical_trials / Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Child / Child, preschool / Female / Humans / Male Idioma: En Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leucemia-Linfoma Linfoblástico de Células Precursoras B / Neoplasia Residual / Antineoplásicos Tipo de estudo: Clinical_trials / Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Child / Child, preschool / Female / Humans / Male Idioma: En Ano de publicação: 2015 Tipo de documento: Article