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Intrapatient variability in concentration/dose ratio of tacrolimus predicts transplant-associated thrombotic microangiopathy

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Abstract

Tacrolimus (TAC) is essential for prophylaxis of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation (allo-HSCT). We have sometimes observed large fluctuations in TAC concentration. However, links between the variability in the concentration or the concentration/dose (C/D) ratio of TAC and clinical complications remain ambiguous. To clarify relationships between various parameters of TAC and early complications such as pre-engraftment immune reactions/engraftment syndrome, aGVHD, and transplant-associated thrombotic microangiopathy (TA-TMA), a total of 146 patients who underwent allo-HSCT were included. Intrapatient variabilities in the concentration and C/D ratio of TAC were estimated by intrapatient mean absolute deviation (iMAD). The mean concentration and C/D ratio of TAC were not significantly different between with and without complications. A strong association was observed between greater iMAD for TAC C/D ratio from days 15 to 21 and the development of TA-TMA. iMAD values for TAC C/D ratio of 11.4 or greater was a risk factor for TA-TMA and the cumulative incidence of nonrelapse mortality (NRM) was significantly higher in patients with iMAD values for TAC C/D ratio of 11.4 or greater. Intrapatient variability in the C/D ratio of TAC was associated with the incidence of TA-TMA and NRM and might be useful for predicting TA-TMA.

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Acknowledgements

KS designed the manuscript. KS, NF, KO, and AK wrote the manuscript. All the authors reviewed the paper and agreed with the final version. We acknowledge all the physicians, nurses, and staff who contributed to the patient care at the Department of Hematology and Oncology in Konan Kosei Hospital.

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The authors have nothing to disclose.

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Authors and Affiliations

  1. Department of Hematology and Oncology, JA Aichi Konan Kosei Hospital, 137, Omatsubara, Takaya-cho, Konan, Aichi, 483-8704, Japan

    Ken Sagou, Nobuaki Fukushima, Shun Ukai, Miyo Goto, Kazutaka Ozeki & Akio Kohno

  2. Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan

    Ken Sagou

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  1. Ken Sagou
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  2. Nobuaki Fukushima
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Correspondence to Ken Sagou.

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Sagou, K., Fukushima, N., Ukai, S. et al. Intrapatient variability in concentration/dose ratio of tacrolimus predicts transplant-associated thrombotic microangiopathy. Int J Hematol 113, 63–72 (2021). https://doi.org/10.1007/s12185-020-02986-8

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  • DOI: https://doi.org/10.1007/s12185-020-02986-8

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