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Causes of death and treatment-related mortality in newly diagnosed childhood acute lymphoblastic leukemia treatment with Chinese Children’s Cancer Group study ALL-2015

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Abstract

To investigate the possible risk factors for death at post-treatment in children with acute lymphoblastic leukemia (ALL). A multivariate competing risk analysis was performed to retrospectively analyze the data of children with ALL who died after treatment with CCCG-ALL-2015 in China and to determine the possible risk factors for death at post-treatment in children with ALL. Age at the first diagnosis of ≥10 years; final risk level of high-risk; D19 minimal residual disease (MRD) (≥0.01%) and D46 MRD (≥0.01%); genetic abnormalities, such as KMT2A-rearrangement, c-Myc rearrangement, and PDGFRB rearrangement; and the presence of CNS3 (all P values, <0.05) were identified as independent risk factors, whereas the risk level at the first diagnosis of low-risk (LR) and ETV6::RUNX1 positivity was considered as independent protective factors of death in children with ALL. Among the 471 cases of death, 45 cases were treated with CCCG-ALL-2015 only, and 163 (34.61%) were treatment-related, with 62.42% due to severe infections. 55.83% of treatment-related mortality (TRM) occurred in the early phase of treatment (induction phase). TRM has a significant impact on the overall survival of pediatric patients with ALL. Moreover, the CCCG-ALL-2015 regimen has a better safety profile for treating children with ALL, with rates close to those in developed countries (registration number: ChiCTR-IPR-14005706; date of registration: June 4, 2014).

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Acknowledgements

We thank the members of the Department of Hematology/Oncology at CCCG for their assistance in data collection.

Funding

This research was supported by the viva China children’s cancer foundation; discipline co-construction project of pediatrics and physiology, grant number 2020lcxk017; the discipline co-construction project of pediatrics and immunology, grant number 2021lcxk030; the Bei**g Bethune Medical Science Research Foundation, grant number sce128en; the clinical research and cultivation program of the second affiliated hospital of Anhui Medical University, grant number 2020lcysocs304. We thank Bullet Edits Limited for Bullet Edits the linguistic editing and proofreading of the manuscript.

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Authors and Affiliations

  1. Department of Pediatrics, The Second Affiliated Hospital of Anhui Medical University, Hefei, China

    Kangkang Liu & Ningling Wang

  2. Department of Hematology/Oncology, Children’s Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China

    **gbo Shao & Hui Jiang

  3. Department of Hematology/Oncology, Shanghai Children’s Medical Center, Shanghai Jiaotong University of School of Medicine, Shanghai, China

    Jiaoyang Cai, **gyan Tang & Shuhong Shen

  4. Department of Hematology/Oncology, Children’s Hospital of Chongqing Medical University, Chongqing, China

    Fengling Xu

  5. Department of Pediatrics, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tian**, China

    Yuanyuan Ren

  6. Department of Pediatrics, Qilu Hospital of Shandong University, **an, China

    Aijun Zhang

  7. Department of Hematology/Oncology, Kunming Children’s Hospital, Kunming, China

    **n Tian

  8. Department of Hematology/Oncology, West China Second Hospital of Sichuan University, Chengdu, China

    **aoqian Lu

  9. Department of Hematology/Oncology, Children’s Hospital of Soochow University, Suzhou, China

    Shaoyan Hu

  10. Department of Pediatrics, Huazhong University of Science and Technology Tongji Medical College Tongji Hospital, Wuhan, China

    Qun Hu

  11. Department of Hematology/Oncology, Guangzhou Women and Children Health Care Center, Guangzhou, China

    Hua Jiang

  12. Department of Pediatrics, Huazhong University of Science and Technology Tongji Medical College Union Hospital, Wuhan, China

    Fen Zhou

  13. Department of Hematology/Oncology, Jiangxi Provincial Children’s Hospital, Nanchang, China

    Changda Liang

  14. Department of Pediatrics, The Chinese University of Hong Kong, Hong Kong Children’s Hospital, Hong Kong, China

    Alex Wing Kwan Leung

  15. Department of Hematology/Oncology, Children’s Hospital of Fudan University, Shanghai, China

    **aowen Zhai

  16. Department of Pediatrics, Nanfang Hospital, Southern Medical University, Guangzhou, China

    Chunfu Li

  17. Department of Hematology/Oncology, Nan**g Children’s Hospital Affiliated to Nan**g Medical University, Nan**g, China

    Yongjun Fang

  18. Department of Pediatrics, Affiliated Hospital of Qingdao University, Qingdao, China

    Zhenling Wang

  19. Department of Hematology/Oncology, Northwest Women’s and Children’s Hospital, **’an, China

    Lu Wen

  20. Department of Pediatrics, **angya Hospital Central South University, Changsha, Hunan, China

    Hui Yang

Authors
  1. Kangkang Liu
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  2. **gbo Shao
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  3. Jiaoyang Cai
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Contributions

All authors contributed to the study conception and design. The structure of this manuscript was conceived and designed by KL, JS, NW, and HJ. The original draft of the manuscript was written by KL. Writing review and editing were performed by KL, NW, and SS. All authors have read and agreed to the final manuscript.

Corresponding authors

Correspondence to Ningling Wang or Hui Jiang.

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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (the hospital ethics committees of The Second Affiliated Hospital of Anhui Medical University (No. SCMCIRB-K2014060) and each collaborative members; China) and with the Helsinki Declaration of 1975, as revised in 2008 and approved by the by the hospital ethics committee of each collaborative member.

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Informed consent was obtained from all patients for being included in the study. Written informed consent has been obtained from the patient(s) to publish this paper.

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The authors declare no competing interests.

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Kangkang Liu and **gbo Shao contributed equally to this work.

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Liu, K., Shao, J., Cai, J. et al. Causes of death and treatment-related mortality in newly diagnosed childhood acute lymphoblastic leukemia treatment with Chinese Children’s Cancer Group study ALL-2015. Ann Hematol 102, 3431–3444 (2023). https://doi.org/10.1007/s00277-023-05389-x

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