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Treosulfan-based conditioning regimen for allogeneic hematopoietic stem cell transplantation in children with non-malignant diseases

Bone Marrow Transplantation volume 57, pages 681–684 (2022)Cite this article

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Hematopoietic stem cell transplantation (HSCT) in non-malignant diseases (NMDs) is challenging, particularly in patients who are young and have pre-existing organ damage, which may lead to increased susceptibility to toxicity [1, 2]. Therefore, less toxic conditioning approaches are needed for patients with NMDs. Treosulfan (L-tritol-1,4-bis-methanesulfonate) is a prodrug of an alkylating agent. It is structurally related to busulfan and has similar myelosuppressive properties, as well as additional immunosuppressive properties. Studies on HSCT in NMD showed that treosulfan-based regimens led to better engraftment and survival outcomes with minimal toxicity [1,2,3,4,5]. Furthermore, some studies showed that the addition of thiotepa to treosulfan-based regimens enhanced engraftment. Naik et al. [6] reported that a single dose of 10 mg/kg thiotepa added to a regimen consisting of fludarabine, melphalan, and alemtuzumab was safe and effective in improving engraftment; all nine patients who received a thiotepa-incorporated regimen achieved sustained engraftment, whereas only 41% of patients who received a regimen without thiotepa had sustained engraftment in a previous study [7].

Thus, we designed a treosulfan and fludarabine-based reduced-toxicity conditioning (RTC) regimen for pediatric patients with NMDs. This regimen consisted of fludarabine (150–180 mg/m2 or 5–6 mg/kg if <12 kg), treosulfan (42 g/m2 or 36 g/m2 if <12 kg), thymoglobuline (rabbit ATG, 5–7.5 mg/kg), and thiotepa (10 mg/kg or 7 mg/kg if <12 kg).

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Fig. 1: Survival outcomes and univariate analysis based on donor type.

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Funding

This work was supported by the Research Program funded by the Korea Disease Control and Prevention Agency (2019-ER6903-02).

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Authors and Affiliations

  1. Department of Pediatrics, Korea Cancer Center Hospital, Korea Institute of Radiological & Medical Sciences, Seoul, Korea

    Jin Kyung Suh

  2. Division of Pediatric Hematology/Oncology, Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul, Korea

    Ho Joon Im, Sung Han Kang, Hyery Kim, Eun Seok Choi & Kyung-Nam Koh

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  1. Jin Kyung Suh
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Contributions

HJI conceived and designed the study, analyzed the data, and wrote the article; JKS collected and analyzed the data and wrote the article; SHK, HK, and KNK treated the patients, collected the clinical data, and wrote and reviewed the article; ESC was responsible for collecting the mononuclear cells and acquiring the related data.

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Correspondence to Ho Joon Im.

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Suh, J.K., Im, H.J., Kang, S.H. et al. Treosulfan-based conditioning regimen for allogeneic hematopoietic stem cell transplantation in children with non-malignant diseases. Bone Marrow Transplant 57, 681–684 (2022). https://doi.org/10.1038/s41409-021-01556-8

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