title: Allogeneic clonal mesenchymal stem cell therapy for refractory graft-versus-host disease to standard treatment: a phase I study.
abstract: Severe graft-versus-host disease (GVHD) is an often lethal complication of allogeneic hematopoietic stem cell transplantation (HSCT). The safety of clinical-grade mesenchymal stem cells (MSCs) has been validated, but mixed results have been obtained due to heterogeneity of the MSCs. In this phase I study, the safety of bone marrow-derived homogeneous clonal MSCs (cMSCs) isolated by a new subfractionation culturing method was evaluated. cMSCs were produced in a GMP facility and intravenously administered to patients who had refractory GVHD to standard treatment resulting after allogeneic HSCT for hematologic malignancies. After administration of a single dose (1×10(6) cells/kg), 11 patients were evaluated for cMSC treatment safety and efficacy. During the trial, nine patients had 85 total adverse events and the rate of serious adverse events was 27.3% (3/11 patients). The only one adverse drug reaction related to cMSC administration was grade 2 myalgia in one patient. Treatment response was observed in four patients: one with acute GVHD (partial response) and three with chronic GVHD. The other chronic patients maintained stable disease during the observation period. This study demonstrates single cMSC infusion to have an acceptable safety profile and promising efficacy, suggesting that we can proceed with the next stage of the clinical trial.
authors.affiliation: Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon 22332, Korea.
authors.forename: Hyeon Gyu
authors.initials: HG
authors.lastname: Yi
authors.affiliation: Department of Internal Medicine, Incheon St. Mary's Hospital, The Catholic University of Korea, Incheon 21431, Korea.
authors.forename: Seung-Ah
authors.initials: SA
authors.lastname: Yahng
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul National University School of Medicine, Seoul 03080, Korea.
authors.forename: Inho
authors.initials: I
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
authors.forename: Je-Hwan
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul 06591, Korea.
authors.forename: Chang-Ki
authors.initials: CK
authors.lastname: Min
authors.affiliation: Translational Research Center, Inha University School of Medicine and SCM Lifescience Co., Ltd., Incheon 22332, Korea.
authors.forename: Jun Hyung
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon 22332, Korea.
authors.forename: Chul Soo
authors.initials: CS
authors.lastname: Kim
authors.affiliation: Translational Research Center, Inha University School of Medicine and SCM Lifescience Co., Ltd., Incheon 22332, Korea.
authors.forename: Sun U
authors.initials: SU
authors.lastname: Song
keywords: Bone marrow; Graft-versus-host disease; Hematopoietic stem cell transplantation; Mesenchymal stem cells