Prognostic significance of minimal residual disease in high risk B-ALL: a report from Children's Oncology Group study AALL0232
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...
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| Vydáno v: | Blood Ročník 126; číslo 8; s. 964 - 971 |
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| Médium: | Journal Article |
| Jazyk: | angličtina |
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United States
20.08.2015
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| ISSN: | 1528-0020 |
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| Abstract | 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. |
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| AbstractList | 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. |
| Author | Winick, Naomi J Devidas, Meenakshi Salzer, Wanda L Dai, Yunfeng Heerema, Nyla A Willman, Cheryl L Raetz, Elizabeth A Nachman, James B Gastier-Foster, Julie M Carroll, Andrew J Larsen, Eric Wood, Brent L Loh, Mignon L Hunger, Stephen P Borowitz, Michael J Carroll, William L |
| Author_xml | – sequence: 1 givenname: Michael J surname: Borowitz fullname: Borowitz, Michael J organization: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD – sequence: 2 givenname: Brent L surname: Wood fullname: Wood, Brent L organization: Department of Laboratory Medicine, University of Washington, Seattle, WA – sequence: 3 givenname: Meenakshi surname: Devidas fullname: Devidas, Meenakshi organization: Department of Biostatistics, Colleges of Medicine and Public Health & Health Professions, University of Florida, Gainesville, FL – sequence: 4 givenname: Mignon L surname: Loh fullname: Loh, Mignon L organization: Benioff Children's Hospital and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA – sequence: 5 givenname: Elizabeth A surname: Raetz fullname: Raetz, Elizabeth A organization: Department of Pediatrics, University of Utah, Salt Lake City, UT – sequence: 6 givenname: Wanda L surname: Salzer fullname: Salzer, Wanda L organization: US Army Medical Research and Materiel Command, Fort Detrick, MD – sequence: 7 givenname: James B surname: Nachman fullname: Nachman, James B organization: Department of Pediatrics, University of Chicago, Chicago, IL – sequence: 8 givenname: Andrew J surname: Carroll fullname: Carroll, Andrew J organization: Department of Genetics, University of Alabama at Birmingham, Birmingham, AL – sequence: 9 givenname: Nyla A surname: Heerema fullname: Heerema, Nyla A organization: Department of Pathology, The Ohio State University School of Medicine, Columbus, OH – sequence: 10 givenname: Julie M surname: Gastier-Foster fullname: Gastier-Foster, Julie M organization: Nationwide Children's Hospital, Columbus, OH – sequence: 11 givenname: Cheryl L surname: Willman fullname: Willman, Cheryl L organization: Cancer Center and Departments of Internal Medicine and Pathology, University of New Mexico, Albuquerque, NM – sequence: 12 givenname: Yunfeng surname: Dai fullname: Dai, Yunfeng organization: Department of Biostatistics, Colleges of Medicine and Public Health & Health Professions, University of Florida, Gainesville, FL – sequence: 13 givenname: Naomi J surname: Winick fullname: Winick, Naomi J organization: University of Texas Southwestern Medical Center, Dallas, TX – sequence: 14 givenname: Stephen P surname: Hunger fullname: Hunger, Stephen P organization: Department of Pediatrics and the Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA – sequence: 15 givenname: William L surname: Carroll fullname: Carroll, William L organization: Department of Pediatrics and The New York University Cancer Institute, New York University Medical Center, New York, NY; and – sequence: 16 givenname: Eric surname: Larsen fullname: Larsen, Eric organization: Maine Children's Cancer Program, Scarborough, ME |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26124497$$D View this record in MEDLINE/PubMed |
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| SubjectTerms | Antineoplastic Agents - administration & dosage Asparaginase - administration & dosage Child Child, Preschool Dexamethasone - administration & dosage Disease-Free Survival Dose-Response Relationship, Drug Female Flow Cytometry Humans Induction Chemotherapy Kaplan-Meier Estimate Leucovorin - administration & dosage Maintenance Chemotherapy Male Methotrexate - administration & dosage Neoplasm, Residual - pathology Polyethylene Glycols - administration & dosage Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - drug therapy Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - mortality Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - pathology Prednisone - administration & dosage Prognosis Proportional Hazards Models Risk Factors |
| Title | Prognostic significance of minimal residual disease in high risk B-ALL: a report from Children's Oncology Group study AALL0232 |
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