title: Bone marrow graft-versus-host disease: evaluation of its clinical impact on disrupted hematopoiesis after allogeneic hematopoietic stem cell transplantation.
abstract: Idiopathic cytopenias are frequently observed in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We have previously reported the effect of graft-versus-host disease (GVHD) on bone marrow (BM) in murine models, indicating that the osteoblast injury mediated by donor T cells was associated with bone marrow suppression and delayed immune reconstitution. In this study, we prospectively evaluated the relevance of these findings in 51 patients. Patients with chronic GVHD manifested the loss of osteoblasts, contributing to cytopenic symptoms (P = .0427 compared with patients without cytopenic symptoms). The loss of osteoblasts was significantly associated with the extensive type of chronic GVHD (P = .012), and flow cytometric analyses revealed lower numbers of CD19(+) B cells and a significantly increased CD4 to CD8 ratio (P = .0002) in these patients. Our data, for the first time to our knowledge, summarize the detailed analyses of the effect of GVHD on BM in the clinical allo-HSCT patients.
authors.affiliation: Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. Electronic address: yusuke@med.hokudai.ac.jp.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Shono
authors.affiliation: Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Souichi
authors.initials: S
authors.lastname: Shiratori
authors.affiliation: Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Mizuha
authors.initials: M
authors.lastname: Kosugi-Kanaya
authors.affiliation: Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ueha
authors.affiliation: Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Sugita
authors.affiliation: Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Shigematsu
authors.affiliation: Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Daigo
authors.initials: D
authors.lastname: Hashimoto
authors.affiliation: Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Fujimoto
authors.affiliation: Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Endo
authors.affiliation: Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Mitsufumi
authors.initials: M
authors.lastname: Nishio
authors.affiliation: Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hashino
authors.affiliation: Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Matsuno
authors.affiliation: Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Matsushima
authors.affiliation: Department of Hematology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Tanaka
authors.affiliation: Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Imamura
authors.affiliation: Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Teshima
mesh_terms: D000328:Adult; D000368:Aged; D018941:Antigens, CD19 / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002452:Cell Count; D002908:Chronic Disease; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D006410:Hematopoiesis / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000276:immunology / Q000473:pathology*; D011446:Prospective Studies; D014184:Transplantation, Homologous
chemical_list: D018941:Antigens, CD19
keywords: Bone marrow graft-versus-host disease (BM GVHD); Idiopathic cytopenias; Osteoblasts