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αβ T-cell-depleted haploidentical hematopoietic cell transplantation and zoledronate/interleukin-2 therapy in children with relapsed, high-risk neuroblastoma

Bone Marrow Transplantation volume 54, pages 348–352 (2019)Cite this article

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Outcomes in patients with relapsed, high-risk neuroblastoma have an extremely poor prognosis and novel treatment options are required [1]. For those patients, haploidentical hematopoietic cell transplantation (haplo-HCT) can be a potential option as it is expected to induce graft-versus-tumor (GVT) effects on neuroblastoma [2, 3]. Limited reports investigating the use of haplo-HCT for neuroblastoma suggested a potential GVT effect, but this was not potent enough to prevent tumor progression in patients with a high tumor burden prior to transplant [4,5,6].

Haplo-HCT using αβ T-cell depletion provides grafts containing many γδ T lymphocytes and other effector cells. γδ T cells can kill tumor cells in an MHC-unrestricted manner without significant risk of graft-versus-host disease (GVHD) [7, 8]. In addition, it can provide a platform for further post-transplant immunotherapy to maximize the GVT effect. Zoledronate, a potent aminobisphosphonate, augments the cytolytic activity of γδ T cells [9]. Interleukin (IL)-2 is also required for the expansion of γδ T cells [10]. Therefore, zoledronate in combination with IL-2 can potentially augment the anti-neuroblastoma activity of γδ T cells, which can be enriched after αβ T-cell-depleted haplo-HCT.

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Funding

This study was supported by grants from the National R&D Program for Cancer Control, Ministry of Health, Welfare and Family Affairs, Republic of Korea Government (grant No. 1520060).

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Authors and Affiliations

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

    Kyung-Nam Koh, Ho Joon Im, Hyery Kim, Eun Seok Choi & Jong Jin Seo

  2. Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

    Nayoung Kim

  3. Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

    Chan-Jeoung Park & Seongsoo Jang

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  1. Kyung-Nam Koh
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Correspondence to Kyung-Nam Koh.

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Koh, KN., Im, H.J., Kim, H. et al. αβ T-cell-depleted haploidentical hematopoietic cell transplantation and zoledronate/interleukin-2 therapy in children with relapsed, high-risk neuroblastoma. Bone Marrow Transplant 54, 348–352 (2019). https://doi.org/10.1038/s41409-018-0305-3

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