Format

Send to

Choose Destination
Blood. 2016 Apr 28;127(17):2101-12. doi: 10.1182/blood-2015-09-670729. Epub 2016 Feb 17.

Dexamethasone vs prednisone in induction treatment of pediatric ALL: results of the randomized trial AIEOP-BFM ALL 2000.

Author information

1
Department of Pediatrics, Christian-Albrechts-University Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany;
2
Division of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany;
3
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;
4
Department of Pediatrics, University of Milano-Bicocca, Ospedale S. Gerardo, Monza, Italy; Centro M. Tettamanti, Clinica Pediatrica Università Milano-Bicocca, Monza, Italy;
5
Department of Pediatrics, St. Anna Children's Cancer Research Institute and St. Anna Children's Hospital, Medical University School, Vienna, Austria;
6
Department of Pediatric Hemato-Oncology, Ospedale Bambin Gesù, Rome, University of Pavia, Pavia, Italy;
7
Centro M. Tettamanti, Clinica Pediatrica Università Milano-Bicocca, Monza, Italy;
8
Department of Pediatric Oncology, University Children's Hospital, Zürich, Switzerland;
9
Direzione Generale, Azienda Sanitaria Provinciale, Ragusa, Italy;
10
Institute of Human Genetics, Ruprecht-Karls-University, Heidelberg, Germany;
11
Division of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany; Department of Pediatric Hematology and Oncology, University Hospital, Essen, Germany;
12
Pediatric Hemato-Oncology, Department of Women's and Children's Health, University of Padova, Padova, Italy;
13
Hematology/Oncology, Robert-Rössle-Klinik at the HELIOS Klinikum, Charité, Berlin, Germany;
14
Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany;
15
Department of Pediatric Hemato-Oncology, Azienda Policlinico-Ospedale Vittorio Emanuele, Catania, Italy;
16
Department of Pediatric Hematology and Oncology, University Hospital, Essen, Germany;
17
Children's Hospital of Eastern Switzerland, St. Gallen, Switzerland;
18
Department of Pediatric Hematology and Oncology, Santobono-Pausilipon Hospital, Napoli, Italy;
19
Pediatric Hematology and Oncology, Justus-Liebig University, Gießen, Germany;
20
Pediatric Hematology and Oncology, Charité Medical Center, Humboldt University, Berlin, Germany;
21
Department of Pediatric Hemato-Oncology, Regina Margherita Children's Hospital, Torino, Italy; and.
22
Department of Pediatric Hematology and Oncology, University Children's Hospital, Münster, Germany.
23
Department of Pediatrics, University of Milano-Bicocca, Ospedale S. Gerardo, Monza, Italy;

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).

PMID:
26888258
DOI:
10.1182/blood-2015-09-670729
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center