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Feasibility of umbilical cord blood transplantation with a myeloablative, reduced toxicity-conditioning regimen

Bone Marrow Transplantation volume 49, pages 980–981 (2014)Cite this article

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Umbilical cord blood transplantation (UCBT) with reduced-intensity conditioning (RIC) has been reported in older patients and/or those with comorbidities who have no suitable related or unrelated donors.1, 2, 3, 4 However, RIC for UCBT has not yet been standardized due to a high rate of graft failure and TRM. To reduce regimen-related toxicity, non-TBI containing regimens that employ agents such as fludarabine (Flu) and either melphalan (Mel) or Bu have been attempted, but are associated with a high rate of graft failure.5,6 In contrast, with CBT using a conditioning regimen consisting of Flu, Mel and TBI, a high rate of TRM has been documented.4 A less toxic conditioning regimen of sufficient intensity to achieve engraftment is therefore required. Flu/Bu-based conditioning has been reported to be less toxic than Flu/Mel-based conditioning.7 Barker et al.2 reported a high rate of graft failure for Flu/oral Bu with 200 cGy TBI. In addition, unlike oral Bu, i.v. Bu is not influenced by variable dose-to-dose bioavailability8 and does not depend on intestinal absorption, which can be disrupted by gastrointestinal complications. It has been suggested that a high Bu concentration is associated with an increased risk of TRM.9 Conversely, a low area under the curve (AUC) regarding Bu level could increase the risk of graft rejection and/or disease relapse. An adequate plasma Bu concentration can lead to sufficient immunosuppression that facilitates engraftment, with a lower rate of disease relapse and less toxicity. We therefore hypothesized that Flu TBI combined with an increased dose of i.v. Bu rather than oral Bu might be a more optimal regimen.

We retrospectively analyzed all patients at our institute who had undergone UCBT with Flu, i.v. Bu, and low-dose TBI between March 2005 and June 2011. Ten patients with a median age of 61 (range 40–68) were evaluated (Table 1). The preparative conditioning regimen consisted of Flu 30 mg/m2/day on days −9 to −4 (total dose, 180 mg/m2), i.v. Bu 0.8 mg/kg every 12 h on days −9 to −5 (total dose, 8 mg/kg) and 400 cGy TBI in two fractions on day −1. In all patients, a single cord unit was transplanted. In most patients, CYA (15 mg/kg twice a day from day −1) and short-term MTX (10 mg/m2 on day 1, 7 mg/m2 on day 3 and 7 mg/m2 on day 5) were used as GVHD prophylaxis. This study was approved by the Institutional Review Board.

Table 1 Patient characteristics and outcomes
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Acknowledgements

This work was supported by a Grant-in-Aid for Scientific Research from the Japanese Ministry of Education, Science, Sports and Culture, and a grant from the Japanese Ministry of Health, Welfare and Labour.

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  1. Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan

    M Nishimoto, H Nakamae, M Nakamae, A Hirose, K Hagihara, H Koh, T Nakane, Y Terada & M Hino

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Correspondence to A Hirose.

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Competing interests

Dr Masayuki Hino has received honoraria from Kyowa Hakko Kirin Co., Ltd, Otsuka Pharmaceutical Co. and Ltd, Sanofi K.K. He has also received research grant and travel support to attend the meeting from Kyowa Hakko Kirin Co., Ltd. Dr Hirohisa Nakamae has received research grant, lecture fees and travel support from Kyowa Hakko Kirin Co., Ltd. He has also received honorarium and travel support from Otsuka Pharmaceutical Co., Ltd. Dr Mika Nakamae has received research grant and travel support from Kyowa Hakko Kirin Co., Ltd. Dr Yoshiki Terada and Hideo Koh have received travel support from Kyowa Hakko Kirin Co., Ltd. Dr Takahiko Nakane has received lecture fee and travel support from Kyowa Hakko Kirin Co., Ltd. Dr Mitsutaka Nishimoto has received travel support from Kyowa Hakko Kirin Co., Ltd. He has also received lecture fees from Otsuka Pharmaceutical Co. and Ltd. The remaining authors declare no conflict of interest.

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Nishimoto, M., Nakamae, H., Nakamae, M. et al. Feasibility of umbilical cord blood transplantation with a myeloablative, reduced toxicity-conditioning regimen. Bone Marrow Transplant 49, 980–981 (2014). https://doi.org/10.1038/bmt.2014.60

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