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Br J Cancer ; 83(11): 1405-11, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11076645

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.


Subject(s)
Bone Marrow Transplantation/immunology , Breast Neoplasms/immunology , Breast Neoplasms/therapy , Graft vs Host Disease/immunology , Graft vs Tumor Effect/immunology , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells/immunology , Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Cyclosporine/adverse effects , Cyclosporine/therapeutic use , Cytotoxicity, Immunologic , Dose-Response Relationship, Drug , Female , Graft vs Host Disease/chemically induced , Humans , Immunosuppressive Agents/therapeutic use , Interferon-gamma/therapeutic use , Killer Cells, Natural/immunology , Lymphocytes/immunology , Middle Aged , Phytohemagglutinins/pharmacology , Survival Analysis , Thiotepa/administration & dosage , Thiotepa/adverse effects
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