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Clinical outcomes of individualized busulfan-dosing in hematopoietic stem cell transplantation in Chinese children undergoing with therapeutic drug monitoring

Bone Marrow Transplantation volume 57, pages 473–478 (2022)Cite this article

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Abstract

To identify relationships between busulfan (Bu) exposure and outcomes of a cohort pediatric patients receiving hematopoietic stem cell transplantation (HSCT), along with a targeted busulfan-based conditioning regimen. We retrospectively evaluated targeted busulfan concentrations in 53 pediatric patients (age 0.4–16 years) who received busulfan 4 times daily according to recommended weight-based doses in a single-center analysis between 2018 and 2020. In this trial, individual busulfan pharmacokinetics were performed following dose 5 of the conditioning regimen. Twenty four of 53 patients (45.3%) studies did not require dose adjustments. Equal number of patients (24/53) required one dose adjustments while two-dose adjustment applied for 5 of 53 (9.4%). Twenty-one percent of the patients exhibited ll-lV aGVHD. The incidence of veno-occlusive disease (VOD) was in 3.8% of the 53 patients, while incidence of hemorrhagic cystitis (II–III) reached to 9.7%. Engraftment was successful in 98% of the 53 patients with relapse in 2% of cases. The probability of overall survival and disease-free survival at day 100 was 96% and 94%, respectively. In conclusion, therapeutic drug monitoring (TDM) and individualization of Bu dosage are essential to improve the efficacy and safety of busulfan-based regimen in Chinese pediatric HSCT recipients.

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Fig. 1: Approximate total AUC of busulfan in relation to underlying disease.
Fig. 2: Mean AUC of busulfan in relation to age (•) VOD.
Fig. 3: Mean AUC of busulfan in relation to weight (•) VOD.
Fig. 4: Occurrence of GVHD in relation to approximate total AUC of busulfan.

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Data availability

The datasets used during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors would like to thank the children and their parents who have participated in this research. Extreme gratitude also goes out to the staff nurses of Pediatric Hematology and Oncology, for their very precise work in sample collection and incredible care of our beloved patients. The authors acknowledge the staff of experimental center and Clinical Pharmacy of Hospital of Capital Institute of Pediatrics and the Medical Laboratory of Beijing Boren Hospital.

Funding

This work was partly supported by grants from the youth development program of Capital Institute of Pediatrics (PY-2017-03), young backbone individual project of Beijing Excellent Talents Training Fund (2017000021469G247).

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Authors and Affiliations

  1. Department of Hematology and Oncology, Children’s Hospital of Capital Institute of Pediatrics, No. 2, Yabao Road, Chaoyang District, Beijing, 100020, China

    Duan-fang Shao, Jun-hui Li, Tao Hu, Zhao-xia Zhang, lei Zhang, Juan-juan li, Jing Cao, Shun-qiao Feng, Rui-hong Tang, Di-xiao Zhong, Ze-liang Song, Mei Yue, Meng-ze Hu, Li-tian Xuan, Meng-na Zhai, Xiao-dong Shi & Rong Liu

  2. Department of experimental center, Children’s Hospital of Capital Institute of Pediatrics, No. 2, Yabao Road, Chaoyang District, Beijing, 100020, China

    Hai-feng Zhang

  3. Department of Clinical Pharmacology, Children’s Hospital of Capital Institute of Pediatrics, No. 2, Yabao Road, Chaoyang District, Beijing, 100020, China

    Xiang-yan Wang

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  1. Duan-fang Shao
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Contributions

RL and X-DS designed the research; DFS performed the research, analyzed the data, and wrote the manuscript; JL, TH, Z-XZ, lZ, Jl, JC, SF, RT, DZ, ZS, MY, MH, lX, and MZ contributed to the patient recruitment and treatment; HZ and XW detected some Bu concentrations and collected some samples, respectively, and all authors gave final approval for the manuscript.

Corresponding authors

Correspondence to Xiao-dong Shi or Rong Liu.

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The authors declare no competing interests.

Ethics approval and consent to participate

The study was conducted in accordance with the Declaration of Helsinki. Guardians and/or patients provided written informed consent before study procedures began. The protocol was approved by institutional review boards at Children’s Hospital of Capital Institute of Pediatrics.

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Shao, Df., Li, Jh., Hu, T. et al. Clinical outcomes of individualized busulfan-dosing in hematopoietic stem cell transplantation in Chinese children undergoing with therapeutic drug monitoring. Bone Marrow Transplant 57, 473–478 (2022). https://doi.org/10.1038/s41409-021-01545-x

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