Phase I trial of intravenous cyclosporine to induce graft-versus-host disease in women undergoing autologous bone marrow transplantation for breast cancer.
OBJECTIVE
We investigated if graft-versus-host disease (GVHD), which is associated with an antitumor effect, could be induced in women with advanced breast cancer by treatment with cyclosporine (CSA) following reinfusion of purged autologous marrow after treatment with high-dose chemotherapy and defined the toxicities of this approach.


METHODS
Fifty-one women with advanced breast cancer responding to therapy were treated with escalating doses of CSA (1.0, 2.5, or 3.75 mg/kg/d) for 28 days following high-dose chemotherapy and autologous bone marrow transplantation and monitored for induction of GVHD and toxicity of therapy.


RESULTS
GVHD was induced in a dose-dependent fashion in 14%, 68%, and 92% of patients at each dose level, respectively, a median of 15 days following autologous marrow reinfusion. GVHD was clinically mild and limited to skin. Toxicity was acceptable, with two deaths within 50 days of marrow reinfusion. Statistically significant increases in maximum creatinine and bilirubin levels were seen at all dose levels when compared with similarly treated historic controls who did not receive CSA. Time to last platelet transfusion was significantly delayed in patients treated at the highest dose.


CONCLUSIONS
GVHD can be safely induced by treatment with CSA in women with advanced breast cancer who are receiving high-dose alkylating agents and autologous bone marrow transplantation. The toxicity of this approach is acceptable. Evidence of antitumor efficacy awaits further investigation.
Kennedy
M J
MJ
Johns Hopkins Oncology Center, Baltimore, MD 21287.
Vogelsang
G B
GB
Beveridge
R A
RA
Farmer
E R
ER
Altomonte
V
V
Huelskamp
A M
AM
Davidson
N E
NE
D000328:Adult; D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation; D001943:Breast Neoplasms / Q000601:surgery / Q000628:therapy*; D003131:Combined Modality Therapy; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006086:Graft vs Host Disease / Q000139:chemically induced*; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D014182:Transplantation, Autologous
D016572:Cyclosporine