Severe steroid‐related neuropsychiatric symptoms during paediatric acute lymphoblastic leukaemia therapy—An observational Ponte di Legno Toxicity Working Group Study

Author:

Anastasopoulou Stavroula12ORCID,Swann Gemma3,Andres‐Jensen Liv4,Attarbaschi Andishe56ORCID,Barzilai‐Birenboim Shlomit7,Erdelyi Daniel J.8,Escherich Gabriele9ORCID,Hamadeh Lina10,Harila Arja11,Lopez‐Lopez Elixabet1213ORCID,McGowan Sheena3,Möricke Anja14,Putti Caterina15,Sagi Judit C.1617,Schmiegelow Kjeld418,Ullrich Nicole J.19,van der Sluis Inge M.20ORCID,Wahid Qurat‐ul‐Ain3,Winick Naomi21,Sramkova Lucie22,Zalcberg Yair23,Zapotocka Ester22,Bhojwani Deepa24ORCID,Halsey Christina3ORCID,

Affiliation:

1. Astrid Lindgren Children's Hospital Karolinska University Hospital Stockholm Sweden

2. Childhood Cancer Research Unit, Department of Women's and Children's Health Karolinska Institutet Stockholm Sweden

3. Wolfson Wohl Cancer Research Centre, School of Cancer Sciences, College of Medical, Veterinary and Life Sciences University of Glasgow Glasgow Scotland

4. Department of Pediatrics and Adolescent Medicine University Hospital Rigshospitalet Copenhagen Denmark

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

6. St. Anna Children's Cancer Research Institute Vienna Austria

7. Department of Pediatric Hematology‐Oncology, Schneider Children's Medical Center of Israel, and Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel

8. Department of Paediatrics Semmelweis University Budapest Hungary

9. University Medical Centre Hamburg‐Eppendorf Clinic of Paediatric Haematology and Oncology Hamburg Germany

10. Wolfson Childhood Cancer Research Centre, Northern Institute for Cancer Research Newcastle University Newcastle upon Tyne UK

11. Department of Women's and Children's Health Uppsala University Uppsala Sweden

12. Department of Biochemistry and Molecular Biology, Faculty of Science and Technology University of the Basque Country (UPV/EHU) Leioa Spain

13. Pediatric Oncology Group Biobizkaia Health Research Institute Barakaldo Spain

14. Department of Pediatrics I, Pediatric Hematology/Oncology, ALL‐BFM Study Group Christian Albrechts University Kiel and University Hospital Schleswig‐Holstein Kiel Germany

15. Department of Woman and Child Health, Clinic of Pediatric Haematology‐Oncology University of Padova Padova Italy

16. Department of Genetics, Cell and Immunobiology Semmelweis University Budapest Hungary

17. Institute of Genomic Medicine and Rare Disorders Semmelweis University Budapest Hungary

18. Institute of Clinical Medicine, Faculty of Medicine University of Copenhagen Copenhagen Denmark

19. Department of Neurology, Boston Children's Hospital Harvard Medical School Boston Massachusetts USA

20. Princess Maxima Center for Pedatric Oncology Utrecht the Netherlands

21. University of Texas Southwestern Medical Center Dallas Texas USA

22. Department of Pediatric Hematology and Oncology, Second Faculty of Medicine Charles University and University Hospital Motol Prague Czech Republic

23. Maccabi Healthcare Services and Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel

24. Children's Hospital Los Angeles, Keck School of Medicine and Norris Comprehensive Cancer Center University of Southern California California Los Angeles USA

Abstract

SummarySteroids are a mainstay in the treatment of acute lymphoblastic leukaemia (ALL) in children and adolescents; however, their use can cause clinically significant steroid‐related neuropsychiatric symptoms (SRNS). As current knowledge on SRNS during ALL treatment is limited, we mapped the phenotypes, occurrence and treatment strategies using a database created by the international Ponte di Legno Neurotoxicity Working Group including data on toxicity in the central nervous system (CNS) in patients treated with frontline ALL protocols between 2000 and 2017. Ninety‐four of 1813 patients in the CNS toxicity database (5.2%) experienced clinically significant SRNS with two peaks: one during induction and one during intensification phase. Dexamethasone was implicated in 86% of SRNS episodes. The most common symptoms were psychosis (52%), agitation (44%) and aggression (31%). Pharmacological treatment, mainly antipsychotics and benzodiazepines, was given to 87% of patients while 38% were hospitalised due to their symptoms. Recurrence of symptoms was reported in 29% of patients and two previously healthy patients required ongoing pharmacological treatment at the last follow up. Awareness of SRNS during ALL treatment and recommendation on treatment strategies merit further studies and consensus.

Funder

Barncancerfonden

CHILDREN with CANCER UK

Cancer Research UK

Publisher

Wiley

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