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Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP-BFM ALL 2000 study

The Associazione Italiana di Ematologia Oncologia Pediatrica and the Berlin-Frankfurt-Münster Acute Lymphoblastic Leukemia (AIEOP-BFM ALL 2000) study has for the first time introduced standardized quantitative assessment of minimal residual disease (MRD) based on immunoglobulin and T-cell receptor...

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Main Authors: Conter, Valentino (Author) , Bartram, Claus R. (Author) , Valsecchi, Maria Grazia (Author) , Schrauder, André (Author) , Panzer-Grümayer, Renate (Author) , Möricke, Anja (Author) , Aricò, Maurizio (Author) , Zimmermann, Martin (Author) , Mann, Georg (Author) , De Rossi, Giulio (Author) , Stanulla, Martin (Author) , Locatelli, Franco (Author) , Basso, Giuseppe (Author) , Niggli, Felix (Author) , Barisone, Elena (Author) , Henze, Günter (Author) , Ludwig, Wolf-Dieter (Author) , Haas, Oskar A. (Author) , Cazzaniga, Giovanni (Author) , Köhler, Rolf (Author) , Silvestri, Daniela (Author) , Bradtke, Jutta (Author) , Parasole, Rosanna (Author) , Beier, Rita (Author) , van Dongen, Jacques J. M. (Author) , Biondi, Andrea (Author) , Schrappe, Martin (Author)
Format: Article (Journal)
Language:English
Published: 14 December 2020
In: Blood
Year: 2010, Volume: 115, Issue: 16, Pages: 3206-3214
ISSN:1528-0020
DOI:10.1182/blood-2009-10-248146
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/blood-2009-10-248146
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Author Notes:Valentino Conter, Claus R. Bartram, Maria Grazia Valsecchi, André Schrauder, Renate Panzer-Grümayer, Anja Möricke, Maurizio Aricò, Martin Zimmermann, Georg Mann, Giulio De Rossi, Martin Stanulla, Franco Locatelli, Giuseppe Basso, Felix Niggli, Elena Barisone, Günter Henze, Wolf-Dieter Ludwig, Oskar A. Haas, Giovanni Cazzaniga, Rolf Koehler, Daniela Silvestri, Jutta Bradtke, Rosanna Parasole, Rita Beier, Jacques J.M. van Dongen, Andrea Biondi, and Martin Schrappe

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245 1 0 |a Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia  |b results in 3184 patients of the AIEOP-BFM ALL 2000 study  |c Valentino Conter, Claus R. Bartram, Maria Grazia Valsecchi, André Schrauder, Renate Panzer-Grümayer, Anja Möricke, Maurizio Aricò, Martin Zimmermann, Georg Mann, Giulio De Rossi, Martin Stanulla, Franco Locatelli, Giuseppe Basso, Felix Niggli, Elena Barisone, Günter Henze, Wolf-Dieter Ludwig, Oskar A. Haas, Giovanni Cazzaniga, Rolf Koehler, Daniela Silvestri, Jutta Bradtke, Rosanna Parasole, Rita Beier, Jacques J.M. van Dongen, Andrea Biondi, and Martin Schrappe 
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520 |a The Associazione Italiana di Ematologia Oncologia Pediatrica and the Berlin-Frankfurt-Münster Acute Lymphoblastic Leukemia (AIEOP-BFM ALL 2000) study has for the first time introduced standardized quantitative assessment of minimal residual disease (MRD) based on immunoglobulin and T-cell receptor gene rearrangements as polymerase chain reaction targets (PCR-MRD), at 2 time points (TPs), to stratify patients in a large prospective study. Patients with precursor B (pB) ALL (n = 3184) were considered MRD standard risk (MRD-SR) if MRD was already negative at day 33 (analyzed by 2 markers, with a sensitivity of at least 10(-4)); MRD high risk (MRD-HR) if 10(-3) or more at day 78 and MRD intermediate risk (MRD-IR): others. MRD-SR patients were 42% (1348): 5-year event-free survival (EFS, standard error) is 92.3% (0.9). Fifty-two percent (1647) were MRD-IR: EFS 77.6% (1.3). Six percent of patients (189) were MRD-HR: EFS 50.1% (4.1; P < .001). PCR-MRD discriminated prognosis even on top of white blood cell count, age, early response to prednisone, and genotype. MRD response detected by sensitive quantitative PCR at 2 predefined TPs is highly predictive for relapse in childhood pB-ALL. The study is registered at http://clinicaltrials.gov: NCT00430118 for BFM and NCT00613457 for AIEOP. 
650 4 |a Adolescent 
650 4 |a Antineoplastic Combined Chemotherapy Protocols 
650 4 |a Biomarkers, Tumor 
650 4 |a Child 
650 4 |a Child, Preschool 
650 4 |a Disease-Free Survival 
650 4 |a Gene Rearrangement, B-Lymphocyte 
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650 4 |a Humans 
650 4 |a Infant 
650 4 |a Kaplan-Meier Estimate 
650 4 |a Neoplasm, Residual 
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650 4 |a Prognosis 
650 4 |a Receptors, Antigen, B-Cell 
650 4 |a Receptors, Antigen, T-Cell 
650 4 |a Remission Induction 
650 4 |a Reverse Transcriptase Polymerase Chain Reaction 
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