The induction of immunologic hyporesponsiveness by preoperative donor-specific transfusions and cyclosporine in human cadaveric transplants. A preliminary trial.
A prospective randomized preliminary trial was performed in patients undergoing cadaveric renal transplantation to determine the potential benefits, disadvantages, and logistic problems associated with the administration of donor-specific transfusions and cyclosporine initiated 24 hr before transplantation. Ten patients received DST followed by continuous intravenous CsA approximately 24 hr before cadaveric renal transplantation from the same donor. Twelve patients receiving sequential therapy with Minnesota antilymphoblast globulin, azathioprine, and steroids with subsequent conversion to CsA served as controls. Patient demographics and the donor characteristics were evenly matched in the two groups. While the study group had longer cold ischemia time and more evidence of renal dysfunction within the first two weeks, subsequent renal function was identical in the groups and there were fewer episodes of severe rejection requiring treatment with OKT3 within the first six months in the DST group (5 vs. 0, P less than 0.05), which also had less reactivity in mixed lymphocyte cultures against preserved donor-specific lymphocytes than did the control group (stimulation index 9.0 +/- 3.0 vs. 25.3 +/- 6.0, respectively, P less than 0.05). The need for dialysis, incidence of infections and other complications, and subsequent immunosuppressive therapy were not different in the two groups. It is concluded that DSTs and intravenous CsA initiated 24 hr prior to transplantation are capable of inducing reduced immunologic responsiveness against the specific donor. Patients treated with this therapy should receive organs from "ideal" donors without risk factors and cold ischemia time should not exceed 30 hr. Further clinical studies of this approach are warranted.
Department of Surgery, University of Cincinnati College of Medicine, Ohio 45267-0558.
J W
JW
Alexander
G F
GF
Babcock
M R
MR
First
C B
CB
Davies
R L
RL
Madden
R
R
Munda
I
I
Penn
J P
JP
Fidler
B R
BR
Cofer
G
G
Stephens
D000163:Acquired Immunodeficiency Syndrome / Q000517:prevention & control; D000328:Adult; D001803:Blood Transfusion; D002102:Cadaver; D016572:Cyclosporine / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D000939:Epitopes; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D006505:Hepatitis / Q000517:prevention & control; D006801:Humans; D007109:Immunity / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D016030:Kidney Transplantation / Q000276:immunology* / Q000401:mortality; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D014019:Tissue Donors
D000939:Epitopes; D007166:Immunosuppressive Agents; D016572:Cyclosporine