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Substitution of methotrexate with corticosteroid for acute graft-versus-host disease prevention in transplanted patients who develop methotrexate toxicity

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Abstract

Methotrexate (MTX) toxicity can hamper the administration of all planned doses in acute graft-versus-host disease (GVHD) prophylaxis following allogeneic hematopoietic stem cell transplantation. Reduction or omission of MTX doses results in an increased risk of acute GVHD. In this prospective observational study, we compared the incidence of GVHD and the transplant outcomes between patients who received the full treatment course of MTX (group 1), patients in whom MTX doses were omitted if MTX toxicity developed (group 2), and patients receiving corticosteroid instead of MTX if MTX toxicity developed (group 3). The cumulative incidence of grades II-IV acute GVHD at 100 days post-transplantation was 22.2 % in group 1, 43.6 % in group 2, and 25.0 % in group 3 (P = 0.132). The risk of grades II-IV acute GVHD in group 2 was higher than that in group 1 (hazard ratio (HR) 3.262, P = 0.016), but the risk in group 3 was similar to that in group 1 (HR 0.960, P = 0.890). Group 3 also showed a trend towards a lower risk of chronic GVHD compared to the other groups. The cumulative risk of chronic GVHD at 2 years was 73.9, 71.6, and 33.3 % in groups 1, 2, and 3, respectively (P = 0.084). However, a likely higher relapse incidence and infection-related mortality in group 3 produced a trend towards the lowest relapse-free survival (2-year RFS, 46.3, 49.3, and 25.0 % in groups 1, 2, and 3, respectively; P = 0.329) and overall survival (2-year OS, 45, 52.3, and 25 %, respectively; P = 0.322) in group 3. Although the substitution of MTX with corticosteroid ameliorates the increased risk of GVHD in patients in which it is imperative to omit its dose, its negative impact on relapse and infection risk does not result in favorable transplant outcomes.

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Acknowledgments

This paper was written as part of Konkuk University’s research support program for its faculty on sabbatical leave in 2013.

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  1. Division of Hematology-Oncology, Department of Internal Medicine, Konkuk University School of Medicine, Konkuk University, Seoul, Republic of Korea

    Sung-Yong Kim, Ah Ran Kim, So Young Yoon, Yo-Han Cho & Mark Hong Lee

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  1. Sung-Yong Kim
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Correspondence to Sung-Yong Kim.

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Kim, SY., Kim, A.R., Yoon, S.Y. et al. Substitution of methotrexate with corticosteroid for acute graft-versus-host disease prevention in transplanted patients who develop methotrexate toxicity. Ann Hematol 95, 483–491 (2016). https://doi.org/10.1007/s00277-015-2574-x

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