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ACUTE LYMPHOBLASTIC LEUKEMIA

DNA-TG and risk of sinusoidal obstruction syndrome in childhood acute lymphoblastic leukemia

Leukemia volume 36, pages 555–557 (2022)Cite this article

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DNA-incorporated thioguanine nucleotides (DNA-TG) is a novel and promising target for therapeutic drug monitoring, since it integrates upstream metabolites of thiopurines and methotrexate (MTX) used during maintenance therapy for childhood acute lymphoblastic leukemia (ALL). Lower DNA-TG has been associated with increased risk of relapse, especially in patients who are minimal residual disease positive at the end of induction therapy [1, 2], and thus provides a deeper layer for understanding maintenance efficacy.

The European ALLTogether consortium is currently conducting a randomized trial, testing whether the addition of very low-dosed, slowly titrated, 6-thioguanine (6-TG) to the conventional MTX/6-mercaptopurine (6-MP) maintenance backbone can increase event-free survival in the patient group stratified to intermediate risk-high (risk stratification in ALLTogether described in Supplementary; Supplementary Figs. 1 and 2); a group comprising ~40% of patients, and in which 60% of relapses are expected to occur (Clinicaltrials.gov Identifier: NCT04307576; EudraCT: 2018-001795-38).

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Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This work was supported by The Danish Cancer Society, Childhood Cancer Foundation (Denmark), Childhood Cancer Foundation (Sweden), Nordic Cancer Union, Otto Christensen Foundation, Copenhagen University Hospital Rigshospitalet, and Novo Nordic Foundation. The United Kingdom Medical Research Council funded the UK ALL97 study. Primary childhood leukemia samples used in this study were provided by the Blood Cancer UK Childhood Leukaemia Cell Bank.

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Authors and Affiliations

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

    Linea Natalie Toksvang, Stine Nygaard Nielsen, Jacob Nersting & Kjeld Schmiegelow

  2. Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark

    Kathrine Grell

  3. Leukaemia Research Cytogenetics Group, Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, UK

    Daniel Murdy & Anthony V. Moorman

  4. Great Ormond Street Hospital for Children National Health Service Trust, London, UK

    Ajay Vora

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

    Kjeld Schmiegelow

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  1. Linea Natalie Toksvang
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Contributions

LNT and KS analyzed data and drafted the letter. KG and SNN compiled and analyzed data from the NOPHO ALL2008 maintenance study. JN was responsible for DNA-TG analyses. DM, AM, and AV compiled and analyzed data from UKALL97 and revised the letter. All authors approved the final manuscript.

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Correspondence to Kjeld Schmiegelow.

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The authors declare no competing interests.

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Toksvang, L.N., Grell, K., Nielsen, S.N. et al. DNA-TG and risk of sinusoidal obstruction syndrome in childhood acute lymphoblastic leukemia. Leukemia 36, 555–557 (2022). https://doi.org/10.1038/s41375-021-01420-0

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