title: Protective conditioning for acute graft-versus-host disease.
abstract: BACKGROUND
  Conditioning with total lymphoid irradiation plus antithymocyte serum protects mice against acute graft-versus-host disease (GVHD) after hematopoietic-cell transplantation. We tested this strategy in humans.
  
  
  METHODS
  Thirty-seven patients with lymphoid malignant diseases or acute leukemia underwent an experimental conditioning regimen with 10 doses of total lymphoid irradiation (80 cGy each) plus antithymocyte globulin, followed by an infusion of HLA-matched peripheral-blood mononuclear cells from related or unrelated donors who received granulocyte colony-stimulating factor.
  
  
  RESULTS
  Of the 37 transplant recipients, only 2 had acute GVHD after hematopoietic-cell transplantation. Potent antitumor effects in patients with lymphoid malignant diseases were shown by the change from partial to complete remission. In the transplant recipients who underwent conditioning with total lymphoid irradiation and antithymocyte globulin, the fraction of donor CD4+ T cells that produced interleukin-4 after in vitro stimulation increased by a factor of five, and the proliferative response to alloantigens in vitro was reduced, as compared with normal control subjects and control subjects who underwent conditioning with a single dose of total-body irradiation (200 cGy).
  
  
  CONCLUSIONS
  A regimen of total lymphoid irradiation plus antithymocyte globulin decreases the incidence of acute GVHD and allows graft antitumor activity in patients with lymphoid malignant diseases or acute leukemia treated with hematopoietic-cell transplantation.
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Stanford, Calif, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Lowsky
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Takahashi
authors.forename: Yin Ping
authors.initials: YP
authors.lastname: Liu
authors.forename: Sussan
authors.initials: S
authors.lastname: Dejbakhsh-Jones
authors.forename: F Carl
authors.initials: FC
authors.lastname: Grumet
authors.forename: Judith A
authors.initials: JA
authors.lastname: Shizuru
authors.forename: Ginna G
authors.initials: GG
authors.lastname: Laport
authors.forename: Keith E
authors.initials: KE
authors.lastname: Stockerl-Goldstein
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Johnston
authors.forename: Richard T
authors.initials: RT
authors.lastname: Hoppe
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Bloch
authors.forename: Karl G
authors.initials: KG
authors.lastname: Blume
authors.forename: Robert S
authors.initials: RS
authors.lastname: Negrin
authors.forename: Samuel
authors.initials: S
authors.lastname: Strober
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007938:Leukemia / Q000401:mortality / Q000628:therapy*; D007970:Leukopenia / Q000209:etiology; D015182:Lymphatic Irradiation; D008223:Lymphoma / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D018183:Transplantation Chimera / Q000235:genetics; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*
chemical_list: D000961:Antilymphocyte Serum; D016207:Cytokines