Outcome of adolescent patients with acute lymphoblastic leukaemia aged 10-14 years as compared with those aged 15-17 years: Long-term results of 1094 patients of the AIEOP-BFM ALL 2000 study.


Journal

European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373

Informations de publication

Date de publication:
11 2019
Historique:
received: 06 06 2019
revised: 01 08 2019
accepted: 12 09 2019
pubmed: 21 10 2019
medline: 29 5 2020
entrez: 21 10 2019
Statut: ppublish

Résumé

Adolescents (aged 10-17 years) with acute lymphoblastic leukaemia (ALL) have unfavourable disease features and an inferior outcome when compared with younger children, but it is still unclear if differences in disease biology and prognosis exist between adolescents older or younger than 15 years. We retrospectively analysed outcomes of 1094 adolescents with ALL, aged 10-17 years, treated within the AIEOP-BFM ALL 2000 trial, overall and by the age groups 10-14 and 15-17 years. Compared with younger children (aged 1-9 years, n = 3647), adolescents had a statistically inferior 5-year event-free survival (EFS) [74.6% (1.3) vs. 84.4% (0.6)] and overall survival (OS) [83.4% (1.1) vs. 92.7% (0.4); p < 0.001]. Clinical and biological disease characteristics did not differ between the two subgroups of adolescents, including minimal residual disease (MRD) results during initial therapy, except for ETV6-RUNX1 frequency and gender. With a median follow-up of 8.8 years, the 5-year EFS and OS were 76.2% (1.5) and 84.9% (1.3), respectively, for those aged 10-14 years and 70.0% (2.8) and 78.8% (2.5) for those aged 15-17 years (p = 0.06; 0.05). There was no significant difference in the cumulative incidence of relapses [17.8% (1.4) and 18.3% (2.4); p = 0.98], while the incidence of treatment-related deaths as a first event was 2.6% (0.6) versus 7.4% (1.6) (p < 0.001) with, in particular, a higher incidence in the high-risk arm. Further prospective studies and biological investigations are required to define optimal treatment for adolescents, in particular for those aged 15-17 years. Newer agents (immunotherapy, targeted therapy) in early treatment phases of patients at higher risk of treatment failure could replace most toxic treatment elements, with the aim of reducing both toxicity and the risk of relapses.

Sections du résumé

BACKGROUND
Adolescents (aged 10-17 years) with acute lymphoblastic leukaemia (ALL) have unfavourable disease features and an inferior outcome when compared with younger children, but it is still unclear if differences in disease biology and prognosis exist between adolescents older or younger than 15 years.
METHODS
We retrospectively analysed outcomes of 1094 adolescents with ALL, aged 10-17 years, treated within the AIEOP-BFM ALL 2000 trial, overall and by the age groups 10-14 and 15-17 years.
FINDINGS
Compared with younger children (aged 1-9 years, n = 3647), adolescents had a statistically inferior 5-year event-free survival (EFS) [74.6% (1.3) vs. 84.4% (0.6)] and overall survival (OS) [83.4% (1.1) vs. 92.7% (0.4); p < 0.001]. Clinical and biological disease characteristics did not differ between the two subgroups of adolescents, including minimal residual disease (MRD) results during initial therapy, except for ETV6-RUNX1 frequency and gender. With a median follow-up of 8.8 years, the 5-year EFS and OS were 76.2% (1.5) and 84.9% (1.3), respectively, for those aged 10-14 years and 70.0% (2.8) and 78.8% (2.5) for those aged 15-17 years (p = 0.06; 0.05). There was no significant difference in the cumulative incidence of relapses [17.8% (1.4) and 18.3% (2.4); p = 0.98], while the incidence of treatment-related deaths as a first event was 2.6% (0.6) versus 7.4% (1.6) (p < 0.001) with, in particular, a higher incidence in the high-risk arm.
INTERPRETATION
Further prospective studies and biological investigations are required to define optimal treatment for adolescents, in particular for those aged 15-17 years. Newer agents (immunotherapy, targeted therapy) in early treatment phases of patients at higher risk of treatment failure could replace most toxic treatment elements, with the aim of reducing both toxicity and the risk of relapses.

Identifiants

pubmed: 31629941
pii: S0959-8049(19)30721-X
doi: 10.1016/j.ejca.2019.09.004
pii:
doi:

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

61-71

Informations de copyright

Copyright © 2019 Elsevier Ltd. All rights reserved.

Auteurs

Anna Maria Testi (AM)

Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy. Electronic address: testi@bce.uniroma1.it.

Andishe Attarbaschi (A)

Department of Pediatric Hematology and Oncology, St. Anna Children's Hospital, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria. Electronic address: andishe.attarbaschi@stanna.at.

Maria Grazia Valsecchi (MG)

Center of Biostatistics for Clinical Epidemiology, Department of Health Science, University of Milano-Bicocca, Milano, Italy.

Anja Möricke (A)

Department of Pediatrics, Christian-Albrechts-University Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.

Gunnar Cario (G)

Department of Pediatrics, Christian-Albrechts-University Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.

Felix Niggli (F)

Department of Pediatric Oncology, University Children's Hospital, Zürich, Switzerland.

Daniela Silvestri (D)

Center of Biostatistics for Clinical Epidemiology, Department of Health Science, University of Milano-Bicocca, Milano, Italy; Pediatric Hematology-Oncology Unit, Department of Pediatrics, University of Milano-Bicocca, MBBM Foundation/ASST Monza, Monza, Italy.

Peter Bader (P)

Department of Children and Adolescent Medicine, Children's Hospital, Goethe University, Frankfurt, Germany.

Michaela Kuhlen (M)

Department of Pediatric and Adolescent Medicine, University Children's Hopsital Augsburg, Swabian Children's Cancer Center, Augsburg, Germany.

Rosanna Parasole (R)

Department of Pediatric Hemato-Oncology, A.O.R.N. Santobono-Pausilipon, Naples, Italy.

Maria Caterina Putti (MC)

Department of Woman and Child Health, Laboratory of Haematology-Oncology, University of Padova, Padova, Italy.

Peter Lang (P)

Department of Pediatric Hematology and Oncology, Children's Hospital, Eberhard Karls University, Tübingen, Germany.

Christian Flotho (C)

Department of Pediatric Hematology and Oncology, Children's Hospital, Albert Ludwigs University, Freiburg, Germany.

Georg Mann (G)

Department of Pediatric Hematology and Oncology, St. Anna Children's Hospital, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.

Carmelo Rizzari (C)

Pediatric Hematology-Oncology Unit, Department of Pediatrics, University of Milano-Bicocca, MBBM Foundation/ASST Monza, Monza, Italy.

Elena Barisone (E)

Pediatric Onco-Hematology, Regina Margherita Children's Hospital, AOU Città della Salute e della Scienza, Turin, Italy.

Franco Locatelli (F)

Department of Pediatric Hematology-Oncology, IRCCS "Bambino Gesù" Children's Hospital, Rome, Italy; Department of Pediatrics, Sapienza, University of Rome, Rome, Italy.

Christin Linderkamp (C)

Department of Pediatric Hematology and Oncology, Children's Hospital, Medical School Hannover, Germany.

Melchior Lauten (M)

Department of Pediatric and Adolescent Medicine, Children's Hospital, University of Lübeck, Germany.

Meinolf Suttorp (M)

Department of Pediatrics, Pediatric Hemato-Oncology Unit, Children's Hospital "Carl Gustav Carus", Dresden, Germany.

Martin Zimmermann (M)

Department of Pediatric Hematology and Oncology, Children's Hospital, Medical School Hannover, Germany.

Guiseppe Basso (G)

Italian Institute for Genomic Medicine, Turin, Italy.

Andrea Biondi (A)

Pediatric Hematology-Oncology Unit, Department of Pediatrics, University of Milano-Bicocca, MBBM Foundation/ASST Monza, Monza, Italy.

Valentino Conter (V)

Pediatric Hematology-Oncology Unit, Department of Pediatrics, University of Milano-Bicocca, MBBM Foundation/ASST Monza, Monza, Italy.

Martin Schrappe (M)

Department of Pediatrics, Christian-Albrechts-University Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany.

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