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Busulfan, Fludarabine, and Cyclophosphamide (BFC) conditioning allowed stable engraftment after haplo-identical allogeneic stem cell transplantation in children with adrenoleukodystrophy and mucopolysaccharidosis

Bone Marrow Transplantation volume 53, pages 770–773 (2018)Cite this article

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Inherited metabolic storage diseases (IMDs), in particular the lysosomal and peroxisomal storage diseases, cause progressive organ failure, ultimately leading to death. Allogeneic stem cell transplantation (allo-SCT) can prevent the progression of IMD symptoms by providing a continuous source of normal enzymes from donor derived cells, provided that the enzyme is produced by normal leukocytes [1]. Since 1981, allogeneic bone marrow transplantation from matched related donors or unrelated donors had proven to be beneficial in hundreds of patients with Hurler syndrome [2, 3] and adrenoleukodystrophy (ALD) [4].

However, many children with IMD who could benefit from allogeneic transplantation are currently lacking an appropriately matched donor. The use of haplo-identical related donor allows donor stem cells for transplantation in children-lacking suitable donors in time. Nevertheless, achieving engraftment and full donor chimerism in IMD patients remains a great challenge, even in a matched-sibling setting. At least 20–25% of patients with IMD require a second or even third graft due to primary or secondary graft failure [5]. Therefore, full-intensity myeloablative conditioning has been required for sustained donor cell engraftment in patients with these illnesses, which is usually achieved with a myeloablative dose of busulfan in combination with immune-suppressive drugs (cyclophosphamide) and serotherapy [e.g., anti-thymocyte globulin (ATG)] [6]. Since 2014, our institute has been investigating the safety and feasibility of allo-SCT, including haplo-identical related donor grafts in children with IMD, using the combination of busulfan, fludarabine, and cyclophosphamide (BFC). Here, we report the successful short-term outcomes of this strategy, including the ability to achieve full donor chimerism, which has been a particularly greater challenge for these patients in the past.

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Acknowledgements

Medical editors at Editage provided editing assistance to the authors during the preparation of this manuscript. This work was supported by the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (81621001), the National Natural Science Foundation of China (81530046), and the Science and Technology Project of Guangdong Province of China (2016B030230003).

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Authors and Affiliations

  1. Peking University People’s Hospital, Peking University Institute of Hematology, Beijing, China

    Yao Chen, Lan-Ping Xu, Xiao-Hui Zhang, Huan Chen, Feng-Rong Wang, Kai-Yan Liu & Xiao-Jun Huang

  2. Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation for the Treatment of Hematological Diseases, Beijing, China

    Yao Chen, Lan-Ping Xu, Xiao-Hui Zhang, Huan Chen, Feng-Rong Wang, Kai-Yan Liu & Xiao-Jun Huang

  3. Department of Pediatrics, Peking University People’s Hospital, Beijing, China

    Jiong Qin

  4. Department of Pediatrics, Peking University First Hospital, Beijing, China

    Yan-Ling Yang

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  1. Yao Chen
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Chen, Y., Xu, LP., Zhang, XH. et al. Busulfan, Fludarabine, and Cyclophosphamide (BFC) conditioning allowed stable engraftment after haplo-identical allogeneic stem cell transplantation in children with adrenoleukodystrophy and mucopolysaccharidosis. Bone Marrow Transplant 53, 770–773 (2018). https://doi.org/10.1038/s41409-018-0175-8

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