title: Bone marrow-derived mesenchymal stem cells (JR-031) for steroid-refractory grade III or IV acute graft-versus-host disease: a phase II/III study.
abstract: Following a phase I/II study using mesenchymal stem cells (MSCs; JR-031) for steroid-refractory grade II or III acute graft-versus-host disease (aGVHD), a phase II/III study using the cells focused on steroid-refractory grade III or IV aGVHD was conducted. The number of infused MSCs and the number of MSC infusions were the same as the phase I/II study. No additional immunosuppressant was given for steroid-refractory aGVHD during the course of MSC infusions. Twenty-five patients (grade III, 22 patients and grade IV, 3 patients) were enrolled in this study. At 4 weeks after the first MSC infusions, six (24 %) and nine patients (36 %) achieved a complete response (CR) and partial response (PR), respectively. Durable CR by 24 weeks, which was the primary end-point, was obtained in 12 of 25 patients (48 %). At 52 weeks, 12 patients (48 %) treated with MSCs only (six patients) and MSCs plus additional treatments (six patients) were alive in CR. The survival was significantly better in patients showing overall response (OR; CR+PR) than in those showing no OR at 4 weeks. Adverse effects commonly associated with MSC infusions were not observed. Taken together, our two clinical trials suggest JR-031 to be effective for steroid-refractory aGVHD.
authors.affiliation: Division of Cell Transplantation and Transfusion, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan. muroi-kz@jichi.ac.jp.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Muroi
authors.affiliation: Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Miyamura
authors.affiliation: Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Okada
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Murata
authors.affiliation: Kobe City Medical Center General Hospital, Kobe, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Naokuni
authors.initials: N
authors.lastname: Uike
authors.affiliation: Department of Hematology, National Hospital Organization, Kumamoto Medical Center, Kumamoto, Japan.
authors.forename: Michihiro
authors.initials: M
authors.lastname: Hidaka
authors.affiliation: Department of Pediatrics, Sappro Hokuyu Hospital, Sapporo, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kobayashi
authors.affiliation: Stem Cell Transplantation Center, Hokkaido University Hospital, Sapporo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Imamura
authors.affiliation: Department of Hematology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Tanaka
authors.affiliation: Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.
authors.forename: Kazuteru
authors.initials: K
authors.lastname: Ohashi
authors.affiliation: Department of Hematology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Taniguchi
authors.affiliation: Division of Hematology and Stem Cell Transplantation, Shizuoka Cancer Center, Nagaizumi-cho, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ikeda
authors.affiliation: Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Eto
authors.affiliation: Division of Hematology, Department of Medicine, Jichi Medical University, Shimotsuke, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.affiliation: Data Science Group, Clinical Intelligence Department, Development Division, JCR Pharmaceuticals Co., Ltd, Ashiya, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Yamaoka
authors.affiliation: Division of Genetic Therapeutics, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Keiya
authors.initials: K
authors.lastname: Ozawa
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000628:therapy*; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D011239:Prednisolone / Q000627:therapeutic use; D012720:Severity of Illness Index; D017211:Treatment Failure; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D011239:Prednisolone; D008775:Methylprednisolone
keywords: GVHD; Mesenchymal stem cells; Steroid