title: Dexamethasone vs prednisone in induction treatment of pediatric ALL: results of the randomized trial AIEOP-BFM ALL 2000.
abstract: Induction therapy for childhood acute lymphoblastic leukemia (ALL) traditionally includes prednisone; yet, dexamethasone may have higher antileukemic potency, leading to fewer relapses and improved survival. After a 7-day prednisone prephase, 3720 patients enrolled on trial Associazione Italiana di Ematologia e Oncologia Pediatrica and Berlin-Frankfurt-Münster (AIEOP-BFM) ALL 2000 were randomly selected to receive either dexamethasone (10 mg/m(2) per day) or prednisone (60 mg/m(2) per day) for 3 weeks plus tapering in induction. The 5-year cumulative incidence of relapse (± standard error) was 10.8 ± 0.7% in the dexamethasone and 15.6 ± 0.8% in the prednisone group (P < .0001), showing the largest effect on extramedullary relapses. The benefit of dexamethasone was partially counterbalanced by a significantly higher induction-related death rate (2.5% vs 0.9%, P = .00013), resulting in 5-year event-free survival rates of 83.9 ± 0.9% for dexamethasone and 80.8 ± 0.9% for prednisone (P = .024). No difference was seen in 5-year overall survival (OS) in the total cohort (dexamethasone, 90.3 ± 0.7%; prednisone, 90.5 ± 0.7%). Retrospective analyses of predefined subgroups revealed a significant survival benefit from dexamethasone only for patients with T-cell ALL and good response to the prednisone prephase (prednisone good-response [PGR]) (dexamethasone, 91.4 ± 2.4%; prednisone, 82.6 ± 3.2%; P = .036). In patients with precursor B-cell ALL and PGR, survival after relapse was found to be significantly worse if patients were previously assigned to the dexamethasone arm. We conclude that, for patients with PGR in the large subgroup of precursor B-cell ALL, dexamethasone especially reduced the incidence of better salvageable relapses, resulting in inferior survival after relapse. This explains the lack of benefit from dexamethasone in overall survival that we observed in the total cohort except in the subset of T-cell ALL patients with PGR. This trial was registered at www.clinicaltrials.gov (BFM: NCT00430118, AIEOP: NCT00613457).
authors.affiliation: Department of Pediatrics, Christian-Albrechts-University Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany;
authors.forename: Anja
authors.initials: A
authors.lastname: Möricke
authors.affiliation: Division of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany;
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
authors.affiliation: Medical Statistics Unit, Department of Clinical Medicine and Prevention, University of Milano-Bicocca, Monza, Italy; Department of Pediatrics, University of Milano-Bicocca, Ospedale S. Gerardo, Monza, Italy;
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Valsecchi
authors.affiliation: Division of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany;
authors.forename: Martin
authors.initials: M
authors.lastname: Stanulla
authors.affiliation: Department of Pediatrics, University of Milano-Bicocca, Ospedale S. Gerardo, Monza, Italy; Centro M. Tettamanti, Clinica Pediatrica Università Milano-Bicocca, Monza, Italy;
authors.forename: Andrea
authors.initials: A
authors.lastname: Biondi
authors.affiliation: Department of Pediatrics, St. Anna Children's Cancer Research Institute and St. Anna Children's Hospital, Medical University School, Vienna, Austria;
authors.forename: Georg
authors.initials: G
authors.lastname: Mann
authors.affiliation: Department of Pediatric Hemato-Oncology, Ospedale Bambin Gesù, Rome, University of Pavia, Pavia, Italy;
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.affiliation: Centro M. Tettamanti, Clinica Pediatrica Università Milano-Bicocca, Monza, Italy;
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cazzaniga
authors.affiliation: Department of Pediatric Oncology, University Children's Hospital, Zürich, Switzerland;
authors.forename: Felix
authors.initials: F
authors.lastname: Niggli
authors.affiliation: Direzione Generale, Azienda Sanitaria Provinciale, Ragusa, Italy;
authors.forename: Maurizio
authors.initials: M
authors.lastname: Aricò
authors.affiliation: Institute of Human Genetics, Ruprecht-Karls-University, Heidelberg, Germany;
authors.forename: Claus R
authors.initials: CR
authors.lastname: Bartram
authors.affiliation: Department of Pediatrics, St. Anna Children's Cancer Research Institute and St. Anna Children's Hospital, Medical University School, Vienna, Austria;
authors.forename: Andishe
authors.initials: A
authors.lastname: Attarbaschi
authors.affiliation: Medical Statistics Unit, Department of Clinical Medicine and Prevention, University of Milano-Bicocca, Monza, Italy; Department of Pediatrics, University of Milano-Bicocca, Ospedale S. Gerardo, Monza, Italy;
authors.forename: Daniela
authors.initials: D
authors.lastname: Silvestri
authors.affiliation: Division of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany; Department of Pediatric Hematology and Oncology, University Hospital, Essen, Germany;
authors.forename: Rita
authors.initials: R
authors.lastname: Beier
authors.affiliation: Pediatric Hemato-Oncology, Department of Women's and Children's Health, University of Padova, Padova, Italy;
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
authors.affiliation: Hematology/Oncology, Robert-Rössle-Klinik at the HELIOS Klinikum, Charité, Berlin, Germany;
authors.forename: Richard
authors.initials: R
authors.lastname: Ratei
authors.affiliation: Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany;
authors.forename: Andreas E
authors.initials: AE
authors.lastname: Kulozik
authors.affiliation: Department of Pediatric Hemato-Oncology, Azienda Policlinico-Ospedale Vittorio Emanuele, Catania, Italy;
authors.forename: Luca
authors.initials: L
authors.lastname: Lo Nigro
authors.affiliation: Department of Pediatric Hematology and Oncology, University Hospital, Essen, Germany;
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kremens
authors.affiliation: Children's Hospital of Eastern Switzerland, St. Gallen, Switzerland;
authors.forename: Jeanette
authors.initials: J
authors.lastname: Greiner
authors.affiliation: Department of Pediatric Hematology and Oncology, Santobono-Pausilipon Hospital, Napoli, Italy;
authors.forename: Rosanna
authors.initials: R
authors.lastname: Parasole
authors.affiliation: Pediatric Hematology and Oncology, Justus-Liebig University, Gießen, Germany;
authors.forename: Jochen
authors.initials: J
authors.lastname: Harbott
authors.affiliation: Department of Pediatric Hemato-Oncology, Ospedale Bambin Gesù, Rome, University of Pavia, Pavia, Italy;
authors.forename: Roberta
authors.initials: R
authors.lastname: Caruso
authors.affiliation: Pediatric Hematology and Oncology, Charité Medical Center, Humboldt University, Berlin, Germany;
authors.forename: Arend
authors.initials: A
authors.lastname: von Stackelberg
authors.affiliation: Department of Pediatric Hemato-Oncology, Regina Margherita Children's Hospital, Torino, Italy; and.
authors.forename: Elena
authors.initials: E
authors.lastname: Barisone
authors.affiliation: Department of Pediatric Hematology and Oncology, University Children's Hospital, Münster, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Rössig
authors.affiliation: Department of Pediatrics, University of Milano-Bicocca, Ospedale S. Gerardo, Monza, Italy;
authors.forename: Valentino
authors.initials: V
authors.lastname: Conter
authors.affiliation: Department of Pediatrics, Christian-Albrechts-University Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany;
authors.forename: Martin
authors.initials: M
authors.lastname: Schrappe
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D003907:Dexamethasone / Q000008:administration & dosage / Q000493:pharmacokinetics; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000628:therapy; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy; D011241:Prednisone / Q000008:administration & dosage; D016016:Proportional Hazards Models; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D003907:Dexamethasone; D011241:Prednisone; D008727:Methotrexate