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Radiation-sparing reduced-intensity unrelated umbilical cord blood transplantation for rare hematological disorders in children

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Abstract

Graft failure is a major pitfall of unrelated umbilical cord blood transplantation (CBT) in children with rare hematological disorders other than acute leukemia, such as acquired and inherited bone marrow failure, myelodysplastic syndrome, juvenile myelomonocytic leukemia, and chronic myeloid leukemia. We developed a less-toxic conditioning regimen for CBT that achieves a higher rate of complete donor chimerism, and retrospectively compared it against two other conditioning regimens for CBT performed at our single institution. The engraftment rate with complete donor chimerism was 100% and 5-year event-free survival (5y-EFS) was 90.9% in patients using our latest regimen (n = 11) of reduced-intensity conditioning (RIC) containing fludarabine (Flu) 180 mg/m2, melphalan (MEL) 210 mg/m2, and low-dose rabbit anti-thymocyte globulin (LD-rATG) 2.5 mg/kg without irradiation (regimen C). Outcomes were better than in patients (n = 10) treated with previous regimens involving irradiation (5y-EFS 30.0%, p = 0.004): regimen A, consisting of myeloablative conditioning containing cyclophosphamide (CY) and total body irradiation (TBI) with 8–12 Gy, or regimen B, consisting of RIC with Flu, CY, horse ATG, and thoracoabdominal irradiation (TAI) with 6 Gy. In conclusion, Flu/MEL/LD-rATG (regimen C) without TBI/TAI may be preferable as RIC for unrelated CBT in children with rare hematological disorders.

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Acknowledgements

The authors thank Dr. Hideki Muramatsu and Prof. Yoshiyuki Takahashi for their cooperation with cellular and molecular pathologies.

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Authors and Affiliations

  1. Department of Hematology/Oncology, Osaka Women’s and Children’s Hospital, 840 Murodo, Izumi city, Osaka, 594-1101, Japan

    Akihisa Sawada, Mariko Shimizu, Maho Koyama-Sato, Kohei Higuchi, Yosuke Okada, Kimitoshi Goto, Shota Inoue, Masahiro Yasui & Masami Inoue

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  1. Akihisa Sawada
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  2. Mariko Shimizu
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  3. Maho Koyama-Sato
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  4. Kohei Higuchi
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  5. Yosuke Okada
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  6. Kimitoshi Goto
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  7. Shota Inoue
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  8. Masahiro Yasui
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  9. Masami Inoue
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Contributions

AS designed and performed the research, analyzed data, and wrote the manuscript. MS designed and performed research. MK-S and KH supported research. YO supported statistical analyses. KG, SI, and MY reported data and provided helpful comments. MI supervised the research and manuscript.

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Correspondence to Akihisa Sawada.

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Sawada, A., Shimizu, M., Koyama-Sato, M. et al. Radiation-sparing reduced-intensity unrelated umbilical cord blood transplantation for rare hematological disorders in children. Int J Hematol 115, 269–277 (2022). https://doi.org/10.1007/s12185-021-03254-z

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  • DOI: https://doi.org/10.1007/s12185-021-03254-z

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