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.

نویسندگان

  • 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
  • Martin Schrappe
چکیده

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.

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عنوان ژورنال:
  • Blood

دوره 115 16  شماره 

صفحات  -

تاریخ انتشار 2010