title: Allogeneic stem cell transplantation as treatment for heavily treated, refractory acute graft-versus-host disease after HLA-mismatched stem cell transplantation.
abstract: OBJECTIVE
  No effective treatment has been established for patients with steroid-refractory acute graft-versus-host disease (GVHD). Recently, we demonstrated in a murine tandem bone marrow transplantation model that life-threatening GVHD established by the first bone marrow transplantation was successfully treated by engraftment of a second donor graft after reduced-intensity conditioning. We named the effect by which allografts counteract GVHD "graft-versus-GVHD."
  
  
  METHODS
  To investigate the efficacy of graft-versus-GVHD treatment clinically, 16 patients who developed, after human leukocyte antigen-mismatched stem cell transplantation, severe GVHD, refractory to three to five lines of GVHD-specific treatments, underwent 17 allogeneic stem cell transplantations using reduced-intensity conditioning regimens with grafts from a second donor.
  
  
  RESULTS
  Among the 15 transplantations that could be evaluated, rescue donor grafts were engrafted in 11 cases and rejected in 4 cases. For patients who achieved rescue donor engraftment, the response rate was 90.9% (eight complete response, two partial response, and one stable disease). Six of the eight patients with complete response survived without GVHD symptoms, with a median follow-up of 2128 days. No new development of GVHD by the second graft was observed. No patients had recurrence of the original malignant disease. In contrast, no long-term survivors were observed in patients who rejected rescue donor grafts.
  
  
  CONCLUSIONS
  We propose here a novel graft-versus-GVHD treatment to treat refractory GVHD, and these results strongly suggest that GVHD can be successfully treated by eliminating the harmful lymphocytes responsible for GVHD by a second allogeneic stem cell transplantation.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya City, Hyogo, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ikegame
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yoshihara
authors.forename: Yuki
authors.initials: Y
authors.lastname: Taniguchi
authors.forename: Katsuji
authors.initials: K
authors.lastname: Kaida
authors.forename: Takayuki
authors.initials: T
authors.lastname: Inoue
authors.forename: Masaya
authors.initials: M
authors.lastname: Okada
authors.forename: Kyoko
authors.initials: K
authors.lastname: Taniguchi
authors.forename: Hitomi
authors.initials: H
authors.lastname: Hasei
authors.forename: Hiroya
authors.initials: H
authors.lastname: Tamaki
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Fujioka
authors.forename: Ruri
authors.initials: R
authors.lastname: Kato
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Soma
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Ogawa
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000628:therapy*; D006680:HLA Antigens / Q000276:immunology; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006648:Histocompatibility / Q000276:immunology; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy; D007239:Infections / Q000209:etiology; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D006680:HLA Antigens