Optimal dosage of methotrexate for GVHD prophylaxis in umbilical cord blood transplantation

Abstract

The combination of methotrexate (MTX) and a calcineurin inhibitor is widely used for GVHD prophylaxis in umbilical cord blood transplantation (UCBT). However, the optimal MTX dosage for GVHD prophylaxis in UCBT remains unclear. In the present study, we investigated the impact of MTX dosage on clinical outcomes following UCBT in a single-center retrospective study. Of 70 UCBT recipients included in this study, 37 received MTX at doses of 10 mg/m2 on day 1, and 7 mg/m2 on days 3 and 6 (low-dose MTX: LD-MTX), and 33 received MTX at doses of 15 mg/m2 on day 1, and 10 mg/m2 on days 3 and 6 (standard-dose MTX: SD-MTX), in addition to tacrolimus (TAC). Grade 3–4 acute GVHD and/or transplant-related complications with endothelial cell damage were considered severe transplant-related complications. Univariate analysis findings revealed that the risk of grade 3–4 acute GVHD was significantly lower in the SD-MTX group than in the LD-MTX group (P = 0.013). Multivariate analysis findings revealed that SD-MTX was significantly associated with a lower incidence of severe transplant-related complications (HR = 0.25; 95% CI, 0.07–0.87; P = 0.029). We conclude that SD-MTX in combination with tacrolimus is optimal for GVHD prophylaxis in UCBT.

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Acknowledgements

The authors acknowledge all the physicians, nurses, and other staff who participated in the care of the patients in the Department of Hematology and Oncology at Konan Kosei Hospital.

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Correspondence to Yoshitaka Adachi.

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Adachi, Y., Ozeki, K., Ukai, S. et al. Optimal dosage of methotrexate for GVHD prophylaxis in umbilical cord blood transplantation. Int J Hematol 109, 440–450 (2019). https://doi.org/10.1007/s12185-019-02598-x

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Keywords

  • Methotrexate
  • Graft-versus-host disease
  • Umbilical cord blood transplantation
  • Endothelial cell damage