Autologous graft-versus-host disease induction in advanced breast cancer: role of peripheral blood progenitor cells.
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.
van der Wall
E
E
Bunting-Blaustein Cancer Research Building, Baltimore, MD 21231, USA.
Horn
T
T
Bright
E
E
Passos-Coehlo
J L
JL
Bond
S
S
Clarke
B
B
Altomonte
V
V
McIntyre
K
K
Vogelsang
G
G
Noga
S J
SJ
Davis
J M
JM
Thomassen
J
J
Ohly
K V
KV
Lee
S M
SM
Fetting
J
J
Armstrong
D K
DK
Davidson
N E
NE
Hess
A D
AD
Kennedy
M J
MJ
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
D007166:Immunosuppressive Agents; D010835:Phytohemagglutinins; D007371:Interferon-gamma; D016572:Cyclosporine; D003520:Cyclophosphamide; D013852:Thiotepa