title: The effect of antilymphocyte serum, fractionated donor bone marrow, and cyclosporine on renal allograft survival in mongrel dogs.
abstract: The effect of combined treatment with antilymphocyte serum, fractionated donor bone marrow, and a limited course of cyclosporine on renal allograft survival in mongrel dogs was examined. Recipients were treated with ALS from day -5 to day +7, relative to transplantation on day 0 with an MLR-mismatched donor. Fractionated donor bone marrow cells (BMFr3) obtained by density gradient separation were infused 3-7 days after ALS treatment. CsA treatments were begun either 3-7 days after ALS plus BMFr3 infusion or 3-7 days after treatments with ALS alone. Extended allograft survival was achieved at all CsA doses in BMFr3-infused, ALS-treated recipients. Allografts were sustained throughout the CsA treatment period without rejection in the majority of recipients (6 of 8) receiving ALS plus BMFr3 and CsA at 20 Mg/kg/day for 60 days. By contrast, few grafts were sustained through 30 days of treatment with CsA at 3.2 (1 of 12) or 10 mg/kg/day (2 of 9) in ALS plus BMFr3-treated recipients. Cyclosporine treatment was ineffective at all doses in augmenting allograft prolongation in ALS-treated recipients that did not receive BMFr3. Nearly all (6 of 7) long-term survivors (greater than 180 days) were BMFr3-treated. Peripheral blood lymphocytes or bone marrow cells of these long-term survivors proliferated normally in response to Con A and PWM, and were MLR responsive to third-party cells but did not have reduced MLR responsiveness to donor alloantigen in all cases. These long-term survivors promptly rejected third-party renal allografts without adverse effects on the original transplant's function. These results show that long-term renal allograft survival with specific unresponsiveness to the donor can result from the combined treatment with ALS plus donor BMFr3 and a limited course of CsA.
authors.affiliation: Department of Medical Laboratory Science, Northeastern University, Boston 02115.
authors.forename: W C
authors.initials: WC
authors.lastname: Hartner
authors.forename: T G
authors.initials: TG
authors.lastname: Markees
authors.forename: S R
authors.initials: SR
authors.lastname: De Fazio
authors.forename: W
authors.initials: W
authors.lastname: Khouri
authors.forename: T
authors.initials: T
authors.lastname: Maki
authors.forename: A P
authors.initials: AP
authors.lastname: Monaco
authors.forename: J J
authors.initials: JJ
authors.lastname: Gozzo
mesh_terms: D000818:Animals; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000627:therapeutic use*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006084:Graft Rejection; D006085:Graft Survival / Q000187:drug effects*; D007165:Immunosuppression Therapy / Q000379:methods*; D016030:Kidney Transplantation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed
chemical_list: D000961:Antilymphocyte Serum; D016572:Cyclosporine; D003404:Creatinine