Steroids 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.

Astrid Lindgren Children's Hospital Karolinska University Hospital Stockholm Sweden

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

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

Department of Biochemistry and Molecular Biology Faculty of Science and Technology University of the Basque Country Leioa Spain

Department of Genetics Cell and Immunobiology Semmelweis University Budapest Hungary

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

Department of Paediatrics Semmelweis University Budapest Hungary

Department of Pediatric Hematology and Oncology 2nd Faculty of Medicine Charles University and University Hospital Motol Prague Czech Republic

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

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

Department of Pediatrics 1 Pediatric Hematology Oncology ALL BFM Study Group Christian Albrechts University Kiel and University Hospital Schleswig Holstein Kiel Germany

Department of Pediatrics and Adolescent Medicine University Hospital Rigshospitalet Copenhagen Denmark

Department of Woman and Child Health Clinic of Pediatric Haematology Oncology University of Padova Padova Italy

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

Institute of Clinical Medicine Faculty of Medicine University of Copenhagen Copenhagen Denmark

Institute of Genomic Medicine and Rare Disorders Semmelweis University Budapest Hungary

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

Pediatric Oncology Group Biobizkaia Health Research Institute Barakaldo Spain

Princess Maxima Center for Pedatric Oncology Utrecht the Netherlands

St Anna Children's Cancer Research Institute Vienna Austria

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

University of Texas Southwestern Medical Center Dallas Texas USA

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

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

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