Autologous graft-versus-host disease induction in advanced breast cancer: role of peripheral blood progenitor cells

Br J Cancer. 2000 Dec;83(11):1405-11. doi: 10.1054/bjoc.2000.1499.

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bone Marrow Transplantation / immunology*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / 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
  • Graft vs Host Disease / immunology*
  • Graft vs Tumor Effect / immunology*
  • Hematopoietic Stem Cell Transplantation*
  • Hematopoietic Stem Cells / immunology*
  • 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

Substances

  • Immunosuppressive Agents
  • Phytohemagglutinins
  • Interferon-gamma
  • Cyclosporine
  • Cyclophosphamide
  • Thiotepa