title: Autologous graft-versus-host disease induction in advanced breast cancer: role of peripheral blood progenitor cells.
abstract: The purpose of the present study was to investigate the impact of the use of peripheral blood progenitor cells (PBPCs) on the induction of autologous graft-versus-host disease (GVHD) in patients with advanced breast cancer. 14 women with stage IIIB and 36 women with stage IV breast cancer received cyclosporine (CsA) 2.5 mg kg-1 i.v. daily, d 0-28, and interferon-gamma (IFNg) 0.025 mg/m2 s.c. qod, d7-28, following PBPC-T +/- bone marrow transplantation (BMT). Preceding high-dose chemotherapy consisted of cyclophosphamide 6 g/m2 and thiotepa 800 mg/m2. Histologically proven > or = grade II cutaneous GVHD was induced in18/50 (36%) of patients and was independent of the source of haematopoietic support. In vitro studies showed that post-transplant, 76% of patients had developed auto-cytotoxicity against their own pre-transplant PHA-lymphoblasts. A significant correlation between the occurrence of GVHD > or = grade II and cytolysis was observed in the NK cell-line K562 and the T47D breast cancer cell-line. With a median follow-up of 2(1/2) years, the overall survival (OS) is 58%, the disease-free survival (DFS) 26%, both independent of the development of GVHD and similar to what has been observed in other studies on high-dose chemotherapy in advanced breast cancer. It therefore remains unclear whether the induction of autologous GVHD with the occurrence of auto-cytotoxic lymphocytes can result in an anti-tumour effect in this group of patients.
authors.affiliation: Bunting-Blaustein Cancer Research Building, Baltimore, MD 21231, USA.
authors.forename: E
authors.initials: E
authors.lastname: van der Wall
authors.forename: T
authors.initials: T
authors.lastname: Horn
authors.forename: E
authors.initials: E
authors.lastname: Bright
authors.forename: J L
authors.initials: JL
authors.lastname: Passos-Coehlo
authors.forename: S
authors.initials: S
authors.lastname: Bond
authors.forename: B
authors.initials: B
authors.lastname: Clarke
authors.forename: V
authors.initials: V
authors.lastname: Altomonte
authors.forename: K
authors.initials: K
authors.lastname: McIntyre
authors.forename: G
authors.initials: G
authors.lastname: Vogelsang
authors.forename: S J
authors.initials: SJ
authors.lastname: Noga
authors.forename: J M
authors.initials: JM
authors.lastname: Davis
authors.forename: J
authors.initials: J
authors.lastname: Thomassen
authors.forename: K V
authors.initials: KV
authors.lastname: Ohly
authors.forename: S M
authors.initials: SM
authors.lastname: Lee
authors.forename: J
authors.initials: J
authors.lastname: Fetting
authors.forename: D K
authors.initials: DK
authors.lastname: Armstrong
authors.forename: N E
authors.initials: NE
authors.lastname: Davidson
authors.forename: A D
authors.initials: AD
authors.lastname: Hess
authors.forename: M J
authors.initials: MJ
authors.lastname: Kennedy
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D016026:Bone Marrow Transplantation / Q000276:immunology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000628:therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use; D003602:Cytotoxicity, Immunologic; D004305:Dose-Response Relationship, Drug; D005260:Female; D006086:Graft vs Host Disease / Q000139:chemically induced / Q000276:immunology*; D020350:Graft vs Tumor Effect / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007371:Interferon-gamma / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D016019:Survival Analysis; D013852:Thiotepa / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D007166:Immunosuppressive Agents; D010835:Phytohemagglutinins; D007371:Interferon-gamma; D016572:Cyclosporine; D003520:Cyclophosphamide; D013852:Thiotepa