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-BFMALL 2000 study

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 KoehlerDaniela Silvestri, Jutta Bradtke, Rosanna Parasole, Rita Beier, Jacques J M Van Dongen, Andrea Biondi, Martin Schrappe

Research output: Contribution to journalArticle

Abstract

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. (Blood. 2010;115(16):3206-3214)

Original languageEnglish
Pages (from-to)3206-3214
Number of pages9
JournalBlood
Volume115
Issue number16
DOIs
Publication statusPublished - Apr 22 2010

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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    Conter, V., Bartram, C. R., Valsecchi, M. G., Schrauder, A., Panzer-Grümayer, R., Möricke, A., Aricò, M., Zimmermann, M., Mann, G., De Rossi, G., Stanulla, M., Locatelli, F., Basso, G., Niggli, F., Barisone, E., Henze, G., Ludwig, W. D., Haas, O. A., Cazzaniga, G., ... Schrappe, M. (2010). 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-BFMALL 2000 study. Blood, 115(16), 3206-3214. https://doi.org/10.1182/blood-2009-10-248146