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Safety and efficacy of low-dose methotrexate for pediatric patients with steroid-refractory acute graft-versus-host disease after hematopoietic stem cell transplantation

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Abstract

Low-dose methotrexate (LD-MTX) has long been included in prophylaxis regimens for acute graft-versus-host disease (aGVHD). In addition, LD-MTX is expected as a treatment option to control aGVHD by regulating the cytokine network. In this study, we retrospectively evaluated 35 patients with steroid-refractory acute GVHD to evaluate the safety and efficacy of LD-MTX as a salvage treatment. LD-MTX was administered weekly at a dose of 10 mg/m2. Overall, 13 patients (37 %) achieved complete response and three (9 %) achieved partial response within 4 weeks after LD-MTX was initiated without any additional agents. Resolution of manifestations of aGVHD in each evaluable organ was observed in 12 of the 23 cases (52 %) with skin aGVHD and in eight of the 23 cases (35 %) with GI aGVHD. Neutropenia and thrombocytopenia (grades III and IV) were observed in nine (26 %) and 17 patients (49 %), respectively. Fatal infectious complications occurred in only three patients (9 %) after LD-MTX treatment. Of the 35 patients studied, 22 were alive with a median follow-up of 60 months and an overall survival rate (Kaplan–Meier estimate) was 62 %. LD-MTX seems suitable for salvage therapy and will not increase risk of infection. Further evaluation of the use of LD-MTX as salvage therapy for steroid-refractory acute GVHD is warranted.

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Authors and Affiliations

  1. Department of Pediatrics, National Kyushu Cancer Center, 3-1-1, Notame, Minami-ku, Fukuoka, 811-1395, Japan

    Jiro Inagaki, Reiji Fukano, Yuichi Kodama, Miho Nishimura & Jun Okamura

  2. Institute for Clinical Research, National Kyushu Cancer Center, 3-1-1, Notame, Minami-ku, Fukuoka, 811-1395, Japan

    Mototsugu Shimokawa

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  1. Jiro Inagaki
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  2. Reiji Fukano
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  3. Yuichi Kodama
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  4. Miho Nishimura
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  5. Mototsugu Shimokawa
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  6. Jun Okamura
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Correspondence to Jiro Inagaki.

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Inagaki, J., Fukano, R., Kodama, Y. et al. Safety and efficacy of low-dose methotrexate for pediatric patients with steroid-refractory acute graft-versus-host disease after hematopoietic stem cell transplantation. Ann Hematol 93, 645–651 (2014). https://doi.org/10.1007/s00277-013-1923-x

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  • DOI: https://doi.org/10.1007/s00277-013-1923-x

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