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Reduced dose of MTX for GVHD prophylaxis promotes engraftment and decreases non-relapse mortality in umbilical cord blood transplantation

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Abstract

Although a combination of calcineurin inhibitor and methotrexate (MTX) is used for graft-versus-host disease (GVHD) prophylaxis in umbilical cord blood transplantation (CBT), optimal dose of MTX for CBT remains to be determined.

We conducted a retrospective study to evaluate the safety and efficacy of standard-dose MTX (St-MTX, 15 mg/m2 on day 1 and 10 mg/m2 on days 3 and 6) and mini-dose MTX (Mini-MTX, 5 mg/m2 on days 1, 3 and 6) for GVHD prophylaxis in patients who underwent single unit CBT against hematological malignancies.

Thirty-two and 26 patients received St-MTX and Mini-MTX, respectively. Cumulative incidence of neutrophil engraftment was significantly higher in the Mini-MTX group than in the St-MTX group (88.5% vs 65.6%, P = 0.00448). Cumulative incidences of grade II to IV and grade III to IV of acute graft-versus-host disease (GVHD) were 34.4% and 6.2% in the St-MTX group, and 34.6% and 7.7% in the Mini-MTX group with no statistical significance. One-year non-relapse mortality (NRM) was significantly lower in the Mini-MTX group compared to the St-MTX group (31.2% vs 3.8%, P = 0.00938), whereas relapse rate was not different between the groups. Multivariate analysis also indicated that Mini-MTX significantly improved engraftment (HR, 0.5359; 95% CI, 0.3082 to 0.9318; P = 0.0270) and reduced NRM (HR, 0.117; 95% CI, 0.0151 to 0.9067; P = 0.040).

Our study suggests that GVHD prophylaxis using Mini-MTX in CBT is feasible and associated with improvement of engraftment and reduction in NRM.

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Acknowledgments

This work was in part supported by North Japan Hematology Study Group.

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Authors and Affiliations

  1. Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan

    Souichi Shiratori, Hiroyuki Ohigashi, Shuichiro Takahashi, Takahide Ara, Hideki Goto, Masao Nakagawa, Junichi Sugita, Masahiro Onozawa, Kaoru Kahata, Tomoyuki Endo, Daigo Hashimoto & Takanori Teshima

  2. Department of Hematology, Hokkaido University Faculty of Medicine, Kita-15 Nishi-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan

    Souichi Shiratori

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Day of neutrophil engraftment after CBT in the St-MTX (n = 21) and Mini-MTX groups (n = 23). (JPG 210 kb)

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Shiratori, S., Ohigashi, H., Takahashi, S. et al. Reduced dose of MTX for GVHD prophylaxis promotes engraftment and decreases non-relapse mortality in umbilical cord blood transplantation. Ann Hematol 99, 591–598 (2020). https://doi.org/10.1007/s00277-020-03937-3

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