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Prognostic impact of the dosage of methotrexate combined with tacrolimus for graft-versus-host disease prophylaxis after cord blood transplantation

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Abstract

The optimal dosage of methotrexate (MTX) for graft-versus-host disease (GVHD) prophylaxis after cord blood transplantation (CBT) has not been well elucidated. Therefore, we conducted a retrospective study comparing a mini-MTX group (5 mg/m2 on day 1, 3 and 6) to a short-MTX group (10 mg/m2 on day 1 and 7 mg/m2 on day 3 and 6) after CBT. Sixty-three patients were classified as the mini-MTX group and 20 as the short-MTX group. The median time and cumulative incidence of neutrophil engraftment did not vary between the two groups. The cumulative incidence of grade 2–4 and grade 3–4 acute GVHD was similar in both groups. Overall survival in the mini-MTX group was significantly lower than in the short-MTX group (46.9% vs. 88.7% at 1 year, p < 0.01), contributing to higher non-relapse mortality (NRM) in the mini-MTX group (32.0% vs. 5.0% at 1 year, p = 0.02). In multivariate analysis, the mini-MTX regimen was the most powerful prognostic factor for OS (hazard ratio 4.11; p = 0.03). Although the reduced dosage of MTX had no effect on neutrophil engraftment, increased NRM due to higher incidence of infection, graft failure, and severe acute GVHD resulted in a lower survival rate in the mini-MTX group after CBT.

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Acknowledgements

The authors would like to thank all patients and their families. We also thank all the physicians, nurses, pharmacists, rehabilitation therapists and support staff for caring for the patients in this study. The following investigators contributed to this study: K. Shigeno, K. Ichinohe, A. Yoda and Y. Ito [Hamamatsu Medical Center], Y. Fukatsu, S. Uchiyama, K. Nakano [Iwata City Hospital], K. Nara, I. Hirano, F. Takagi [Seirei Mikatahara General Hospital], S. Fujisawa, M. Nakata, C. Honma [Seirei Hamamatsu General Hospital], and Y. Sugimoto [Kikugawa General Hospital].

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Authors and Affiliations

  1. Division of Hematology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan

    Miwa Adachi, Hiroya Hirata, Katsumi Koyauchi, Satoshi Dohtan, Shinichiro Oka, Nami Sakamoto, Masamitsu Takaba, Tomonari Takemura, Yasuyuki Nagata & Takaaki Ono

  2. Division of Hematology, Hamamatsu Medical Center, Hamamatsu, Japan

    Daisuke Yokota & Kensuke Naito

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  1. Miwa Adachi
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Adachi, M., Yokota, D., Hirata, H. et al. Prognostic impact of the dosage of methotrexate combined with tacrolimus for graft-versus-host disease prophylaxis after cord blood transplantation. Int J Hematol 114, 252–262 (2021). https://doi.org/10.1007/s12185-021-03161-3

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  • DOI: https://doi.org/10.1007/s12185-021-03161-3

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