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
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, 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
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 https://ichgcp.net/clinical-trials-registry/NCT00430118" title="See in ClinicalTrials.gov">NCT00430118 for BFM and NCT00613457 for AIEOP.
Source: PubMed