Scylla and Charybdis: Unpalatable choices in managing hypodiploid acute lymphoblastic leukemia

John N. Colgan; Noemi A. Fuentes-Bolanos; Draga Barbaric; Luciano Dalla-Pozza; Richard Mitchell; Sujith Samarasinghe; Martin Schrappe; Katherine M. Tucker; Kjeld Schmiegelow; Toby N. Trahair

EJC Paediatric Oncology (Dec 2023)

Scylla and Charybdis: Unpalatable choices in managing hypodiploid acute lymphoblastic leukemia

John N. Colgan,
Noemi A. Fuentes-Bolanos,
Draga Barbaric,
Luciano Dalla-Pozza,
Richard Mitchell,
Sujith Samarasinghe,
Martin Schrappe,
Katherine M. Tucker,
Kjeld Schmiegelow,
Toby N. Trahair

Affiliations

John N. Colgan: Kids Cancer Centre, Sydney Children’s Hospital, High Street, Randwick, NSW, Australia; Children’s Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, NSW, Australia; Discipline of Paediatrics and Child Health, School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Kensington, NSW, Australia
Noemi A. Fuentes-Bolanos: Kids Cancer Centre, Sydney Children’s Hospital, High Street, Randwick, NSW, Australia; Children’s Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, NSW, Australia; Discipline of Paediatrics and Child Health, School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Kensington, NSW, Australia
Draga Barbaric: Kids Cancer Centre, Sydney Children’s Hospital, High Street, Randwick, NSW, Australia
Luciano Dalla-Pozza: Cancer Centre for Children, the Children’s Hospital at Westmead, Westmead, NSW, Australia
Richard Mitchell: Kids Cancer Centre, Sydney Children’s Hospital, High Street, Randwick, NSW, Australia; Discipline of Paediatrics and Child Health, School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Kensington, NSW, Australia
Sujith Samarasinghe: Department of Haematology, Great Ormond Street Hospital, London, United Kingdom
Martin Schrappe: Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
Katherine M. Tucker: Kids Cancer Centre, Sydney Children’s Hospital, High Street, Randwick, NSW, Australia
Kjeld Schmiegelow: Pediatric and Adolescent Medicine, Juliane Marie Centre, Rigshospitalet, Copenhagen, Denmark; Faculty of Health Sciences, University of Copenhagen and the Pediatric Clinic, Juliane Marie Centre, Rigshospitalet, Copenhagen, Denmark
Toby N. Trahair: Kids Cancer Centre, Sydney Children’s Hospital, High Street, Randwick, NSW, Australia; Children’s Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, NSW, Australia; Discipline of Paediatrics and Child Health, School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Kensington, NSW, Australia; Corresponding author at: Kids Cancer Centre, Sydney Children’s Hospital, High Street, Randwick, NSW, Australia.

Journal volume & issue: Vol. 2
p. 100133

Abstract

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Acquired TP53 alterations are present in > 90% of cases of paediatric low-hypodiploid acute lymphoblastic leukaemia (ALL), and ≈ 50% of patients with this subtype harbor germline pathogenic / likely pathogenic (P/LP) TP53 alterations. Despite dose intensified, conventional chemotherapy, survival in low-hypodiploid ALL remains dismal compared to other paediatric ALL. Individuals with underlying Li-Fraumeni Syndrome (LFS) are known to have increased sensitivity to genotoxic effect of chemotherapy and radiotherapy. Recent evidence shows a 25.1% 5-year cumulative incidence of SMNs post ALL therapy in an LFS population as compared to 0.7% in patients with either a wild type or VUS TP53. The parallel high risks of both relapse and SMN present unpalatable choices facing clinicians.

Published in EJC Paediatric Oncology

ISSN: 2772-610X (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.sciencedirect.com/journal/ejc-paediatric-oncology

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