title: Chronic graft-versus-host disease after granulocyte colony-stimulating factor-mobilized allogeneic stem cell transplantation: the role of donor T-cell dose and differentiation.
abstract: The use of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood as a source of stem cells has resulted in a high incidence of severe chronic graft-versus-host disease (cGVHD), which compromises the outcome of clinical allogeneic stem cell transplantation. We have studied the effect of G-CSF on both immune complex and fibrotic cGVHD directed to major (DBA/2 --> B6D2F1) or minor (B10.D2 --> BALB/c) histocompatibility antigens. In both models, donor pretreatment with G-CSF reduced cGVHD mortality in association with type 2 differentiation. However, after escalation of the donor T-cell dose, scleroderma occurred in 90% of the recipients of grafts from G-CSF-treated donors. In contrast, only 11% of the recipients of control grafts developed scleroderma, and the severity of hepatic cGVHD was also reduced. Mixing studies confirmed that in the presence of high donor T-cell doses, the severity of scleroderma was determined by the non-T-cell fraction of grafts from G-CSF-treated donors. These data confirm that the induction of cGVHD after donor treatment with G-CSF is dependent on the transfer of large numbers of donor T cells in conjunction with a putatively expanded myeloid lineage, providing a further rationale for the limitation of cell dose in allogeneic stem cell transplantation.
authors.affiliation: The Queensland Institute of Medical Research, Herston, Australia.
authors.forename: Kelli P A
authors.initials: KP
authors.lastname: MacDonald
authors.forename: Vanessa
authors.initials: V
authors.lastname: Rowe
authors.forename: Cheryl
authors.initials: C
authors.lastname: Filippich
authors.forename: Diana
authors.initials: D
authors.lastname: Johnson
authors.forename: Edward S
authors.initials: ES
authors.lastname: Morris
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Clouston
authors.forename: James L M
authors.initials: JL
authors.lastname: Ferrara
authors.forename: Geoffrey R
authors.initials: GR
authors.lastname: Hill
mesh_terms: D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation; D002908:Chronic Disease; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology / Q000401:mortality*; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006649:Histocompatibility Antigens; D008107:Liver Diseases / Q000209:etiology; D017710:Lymphocyte Transfusion / Q000379:methods; D051379:Mice; D008815:Mice, Inbred Strains; D012594:Scleroderma, Localized / Q000209:etiology; D016176:T-Lymphocyte Subsets; D013601:T-Lymphocytes / Q000637:transplantation*; D014184:Transplantation, Homologous
chemical_list: D006649:Histocompatibility Antigens; D016179:Granulocyte Colony-Stimulating Factor