Immunosuppressive efficacy of vincristine in heart transplantation: a preliminary report.
Because vincristine has immunosuppressive activity in animal models, has specific cytotoxic effects on lymphocytes, and does not have overlapping toxicity with other immunosuppressive agents, we designed a prospective randomized trial to evaluate the efficacy of the addition of vincristine to standard immunosuppressive therapy in heart transplantation. Patients received equine antithymocyte globulin for the first week or murine antihuman mature T cell (OKT3) monoclonal antibody for the first 2 weeks after transplantation and were maintained on azathioprine and cyclosporine. A steroid pulse was administered 1 day after completion of antithymocyte globulin or OKT3 monoclonal antibody and tapered off over 21 days. Vincristine was given at 0.025 mg/kg intravenously for eight dosages over 12 weeks, beginning 2 days after completion of antithymocyte globulin or OKT3 monoclonal antibody. Fifty-two patients were randomized (26 were given vincristine, and 26 were not). The addition of vincristine to the regimen of patients receiving antithymocyte globulin resulted in significantly fewer episodes of rejection at 1 month (vincristine, 0.2 +/- 0.1; no vincristine, 1.2 +/- 0.2; p less than 0.001), at 3 months (vincristine, 1.2 +/- 0.1; no vincristine, 2.5 +/- 0.3; p less than 0.001), and at 6 months (vincristine, 1.9 +/- 0.2; no vincristine, 2.9 +/- 0.3; p less than 0.001). It also resulted in significantly more patients being successfully weaned off daily steroids (vincristine, 67%; no vincristine, 20%; p = 0.04). The addition of vincristine to the regimen of patients receiving early rejection prophylaxis with OKT3 monoclonal antibody did not alter rejection incidence or steroid usage.(ABSTRACT TRUNCATED AT 250 WORDS)
Gilbert
E M
EM
Division of Cardiology, University of Utah Medical Center, Salt Lake City 84132.
Renlund
D G
DG
O'Connell
J B
JB
Eiswirth
C C
CC
Rothstein
G
G
Gay
W A
WA
Bristow
M R
MR
D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D001379:Azathioprine / Q000008:administration & dosage; D003524:Cyclosporins / Q000008:administration & dosage; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000187:drug effects*; D016027:Heart Transplantation; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D011446:Prospective Studies; D011897:Random Allocation; D014750:Vincristine / Q000008:administration & dosage* / Q000009:adverse effects
D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D003524:Cyclosporins; D007166:Immunosuppressive Agents; D014750:Vincristine; D001379:Azathioprine; D011241:Prednisone; D006854:Hydrocortisone; D008775:Methylprednisolone