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

Stavroula Anastasopoulou^{1

2}, Gemma Swann³, Liv Andres-Jensen⁴, Andishe Attarbaschi^{5

6}, Shlomit Barzilai-Birenboim⁷, Daniel J Erdelyi⁸, Gabriele Escherich⁹, Lina Hamadeh¹⁰, Arja Harila¹¹, Elixabet Lopez-Lopez^{12

13}, Sheena McGowan³, Anja Möricke¹⁴, Caterina Putti¹⁵, Judit C Sagi^{16

17}, Kjeld Schmiegelow^{4

18}, Nicole J Ullrich¹⁹, Inge M van der Sluis²⁰, Qurat-Ul-Ain Wahid³, Naomi Winick²¹, Lucie Sramkova²², Yair Zalcberg²³, Ester Zapotocka²², Deepa Bhojwani²⁴, Christina Halsey³; Ponte Di Legno Neurotoxicity Working Group

Affiliations

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.

PMID: 38924051
DOI: 10.1111/bjh.19610

Observational Study

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

Stavroula Anastasopoulou et al. Br J Haematol. 2024 Oct.

. 2024 Oct;205(4):1450-1459.

doi: 10.1111/bjh.19610. Epub 2024 Jun 25.

Authors

Affiliations

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.

PMID: 38924051
DOI: 10.1111/bjh.19610

Abstract

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.

Keywords: ALL; children; neuropsychiatric symptoms; steroids.

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References

REFERENCES

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

Affiliations

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

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Abstract

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