title: Safety and efficacy of low-dose methotrexate for pediatric patients with steroid-refractory acute graft-versus-host disease after hematopoietic stem cell transplantation.
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/m(2). 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.
authors.affiliation: Department of Pediatrics, National Kyushu Cancer Center, 3-1-1, Notame, Minami-ku, Fukuoka, 811-1395, Japan, inagakij@nk-cc.go.jp.
authors.forename: Jiro
authors.initials: J
authors.lastname: Inagaki
authors.forename: Reiji
authors.initials: R
authors.lastname: Fukano
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kodama
authors.forename: Miho
authors.initials: M
authors.lastname: Nishimura
authors.forename: Mototsugu
authors.initials: M
authors.lastname: Shimokawa
authors.forename: Jun
authors.initials: J
authors.lastname: Okamura
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000188:drug therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007223:Infant; D007231:Infant, Newborn; D007275:Injections, Intravenous; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D009503:Neutropenia / Q000139:chemically induced / Q000175:diagnosis; D012189:Retrospective Studies; D013256:Steroids / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D013256:Steroids; D008727:Methotrexate