Anna Maria Testi1, Andishe Attarbaschi2, Maria Grazia Valsecchi3, Anja Möricke4, Gunnar Cario4, Felix Niggli5, Daniela Silvestri6, Peter Bader7, Michaela Kuhlen8, Rosanna Parasole9, Maria Caterina Putti10, Peter Lang11, Christian Flotho12, Georg Mann13, Carmelo Rizzari14, Elena Barisone15, Franco Locatelli16, Christin Linderkamp17, Melchior Lauten18, Meinolf Suttorp19, Martin Zimmermann17, Guiseppe Basso20, Andrea Biondi14, Valentino Conter14, Martin Schrappe4. 1. Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy. Electronic address: testi@bce.uniroma1.it. 2. 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. 3. Center of Biostatistics for Clinical Epidemiology, Department of Health Science, University of Milano-Bicocca, Milano, Italy. 4. Department of Pediatrics, Christian-Albrechts-University Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany. 5. Department of Pediatric Oncology, University Children's Hospital, Zürich, Switzerland. 6. 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. 7. Department of Children and Adolescent Medicine, Children's Hospital, Goethe University, Frankfurt, Germany. 8. Department of Pediatric and Adolescent Medicine, University Children's Hopsital Augsburg, Swabian Children's Cancer Center, Augsburg, Germany. 9. Department of Pediatric Hemato-Oncology, A.O.R.N. Santobono-Pausilipon, Naples, Italy. 10. Department of Woman and Child Health, Laboratory of Haematology-Oncology, University of Padova, Padova, Italy. 11. Department of Pediatric Hematology and Oncology, Children's Hospital, Eberhard Karls University, Tübingen, Germany. 12. Department of Pediatric Hematology and Oncology, Children's Hospital, Albert Ludwigs University, Freiburg, Germany. 13. Department of Pediatric Hematology and Oncology, St. Anna Children's Hospital, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria. 14. Pediatric Hematology-Oncology Unit, Department of Pediatrics, University of Milano-Bicocca, MBBM Foundation/ASST Monza, Monza, Italy. 15. Pediatric Onco-Hematology, Regina Margherita Children's Hospital, AOU Città della Salute e della Scienza, Turin, Italy. 16. Department of Pediatric Hematology-Oncology, IRCCS "Bambino Gesù" Children's Hospital, Rome, Italy; Department of Pediatrics, Sapienza, University of Rome, Rome, Italy. 17. Department of Pediatric Hematology and Oncology, Children's Hospital, Medical School Hannover, Germany. 18. Department of Pediatric and Adolescent Medicine, Children's Hospital, University of Lübeck, Germany. 19. Department of Pediatrics, Pediatric Hemato-Oncology Unit, Children's Hospital "Carl Gustav Carus", Dresden, Germany. 20. Italian Institute for Genomic Medicine, Turin, Italy.
Abstract
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.
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.
Authors: Christina Peters; Michael H Albert; Anna Eichinger; Ulrike Poetschger; Evgenia Glogova; Peter Bader; Oliver Basu; Rita Beier; Birgit Burkhardt; Carl-Friedrich Classen; Alexander Claviez; Selim Corbacioglu; Hedwig E Deubzer; Johann Greil; Bernd Gruhn; Tayfun Güngör; Kinan Kafa; Jörn-Sven Kühl; Peter Lang; Bjoern Soenke Lange; Roland Meisel; Ingo Müller; Martin G Sauer; Paul-Gerhardt Schlegel; Ansgar Schulz; Daniel Stachel; Brigitte Strahm; Angela Wawer Journal: Leukemia Date: 2022-09-12 Impact factor: 12.883