Response-guided chemotherapy for pediatric acute myeloid leukemia without hematopoietic stem cell transplantation in first complete remission: Results from protocol DB AML-01.


Journal

Pediatric blood & cancer
ISSN: 1545-5017
Titre abrégé: Pediatr Blood Cancer
Pays: United States
ID NLM: 101186624

Informations de publication

Date de publication:
05 2019
Historique:
received: 26 07 2018
revised: 19 11 2018
accepted: 14 12 2018
pubmed: 10 1 2019
medline: 30 11 2019
entrez: 10 1 2019
Statut: ppublish

Résumé

Children with acute myeloid leukemia (AML) have a 70% survival rate with treatment regimens containing high doses of cytarabine and anthracyclines and, in some, hematopoietic stem cell transplantation (allo-HSCT). In this multicenter Dutch-Belgian protocol (DB AML-01), 112 children with de novo AML were included. Treatment was stratified according to day 15 bone marrow response after the first induction course. Poor responders received a second course without delay while good responders awaited hematological recovery. Patients achieving CR after two induction courses continued with three consolidation courses without HSCT in CR1. The overall remission rate was 93.5%. After a median follow-up of 4.1 years, three-year event-free survival (EFS) was 52.6% (95% CI, 42.9%-61.3%), three-year cumulative incidence of relapse 39.7% (95% CI, 30.1%-49.0%), and three-year overall survival (OS) 74.0% (95% CI, 64.8%-81.2%). Significantly more events occurred in patients with high WBC at diagnosis or FLT3-ITD/NPM1-WT, whereas core binding factor (CBF) leukemia had a significantly better EFS. KMT2A rearrangements and age > 10 years negatively impacted OS. DB AML-01 response-guided therapy results in a favorable OS, particularly for children with CBF leukemia, children younger than 10 years or with initial WBC counts below 100 × 10

Sections du résumé

BACKGROUND
Children with acute myeloid leukemia (AML) have a 70% survival rate with treatment regimens containing high doses of cytarabine and anthracyclines and, in some, hematopoietic stem cell transplantation (allo-HSCT).
PROCEDURE
In this multicenter Dutch-Belgian protocol (DB AML-01), 112 children with de novo AML were included. Treatment was stratified according to day 15 bone marrow response after the first induction course. Poor responders received a second course without delay while good responders awaited hematological recovery. Patients achieving CR after two induction courses continued with three consolidation courses without HSCT in CR1.
RESULTS
The overall remission rate was 93.5%. After a median follow-up of 4.1 years, three-year event-free survival (EFS) was 52.6% (95% CI, 42.9%-61.3%), three-year cumulative incidence of relapse 39.7% (95% CI, 30.1%-49.0%), and three-year overall survival (OS) 74.0% (95% CI, 64.8%-81.2%). Significantly more events occurred in patients with high WBC at diagnosis or FLT3-ITD/NPM1-WT, whereas core binding factor (CBF) leukemia had a significantly better EFS. KMT2A rearrangements and age > 10 years negatively impacted OS.
CONCLUSIONS
DB AML-01 response-guided therapy results in a favorable OS, particularly for children with CBF leukemia, children younger than 10 years or with initial WBC counts below 100 × 10

Identifiants

pubmed: 30623572
doi: 10.1002/pbc.27605
doi:

Substances chimiques

Anthracyclines 0
NPM1 protein, human 0
Cytarabine 04079A1RDZ
Nucleophosmin 117896-08-9

Types de publication

Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e27605

Informations de copyright

© 2019 Wiley Periodicals, Inc.

Auteurs

Barbara De Moerloose (B)

Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium.
Cancer Research Institute Ghent, Ghent, Belgium.

Ardine Reedijk (A)

Dutch Childhood Oncology Group (DCOG), The Hague, the Netherlands.

Geertruida H de Bock (GH)

Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

Tim Lammens (T)

Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium.
Cancer Research Institute Ghent, Ghent, Belgium.

Valerie de Haas (V)

Dutch Childhood Oncology Group (DCOG), The Hague, the Netherlands.

Barbara Denys (B)

Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospital, Ghent, Belgium.

Laurence Dedeken (L)

Department of Pediatric Hematology Oncology, Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, Brussels, Belgium.

Marry M van den Heuvel-Eibrink (MM)

Department of Pediatric Hematology-Oncology, Princess Máxima Center, Utrecht, the Netherlands.
Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands.

Maroeska Te Loo (M)

Department of Pediatric Hematology-Oncology, Radboud University Medical Center, Nijmegen, the Netherlands.

Anne Uyttebroeck (A)

Department of Pediatrics, University Hospital Gasthuisberg, Leuven, Belgium.

An Van Damme (A)

Department of Pediatrics, University Hospital Saint-Luc, Brussels, Belgium.

Jutte Van der Werff-Ten Bosch (J)

Department of Pediatrics, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium.

Jozsef Zsiros (J)

Department of Pediatric Oncology, Amsterdam Medical Center, Emma Children's Hospital, Amsterdam, the Netherlands.

Gertjan Kaspers (G)

Dutch Childhood Oncology Group (DCOG), The Hague, the Netherlands.
Department of Pediatric Hematology-Oncology, Princess Máxima Center, Utrecht, the Netherlands.
Department of Pediatric Oncology, VU University Medical Center, Amsterdam, the Netherlands.

Eveline de Bont (E)

Dutch Childhood Oncology Group (DCOG), The Hague, the Netherlands.
Department of Pediatric Hematology-Oncology, University Medical Center Groningen, Beatrix Children's Hospital, University of Groningen, Groningen, the Netherlands.

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