title: Randomized trial of rATg/Daclizumab vs. rATg/Alemtuzumab as dual induction therapy in renal transplantation: Results at 8years of follow-up.
abstract: Our goal in using dual induction therapy is to bring the kidney transplant recipient closer (through more effectively timed lymphodepletion) to an optimally immunosuppressed state. Here, we report long-term results of a prospective randomized trial comparing (Group I,N=100) rATG/Dac (3 rATG, 2 Dac doses) vs. (Group II,N=100) rATG/Alemtuzumab(C1H) (1 dose each), using reduced tacrolimus dosing, EC-MPS, and early corticosteroid withdrawal. Lower EC-MPS dosing was targeted in Group II to avoid severe leukopenia. Median follow-up was 96mo post-transplant. There were no differences in 1st BPAR (including borderline) rates: 10/100 vs. 9/100 in Groups I and II during the first 12mo(P=0.54), and 20/100 vs. 20/100 throughout the study(P=0.90). Equally favorable renal function was maintained in both treatment arms(N.S.). While not significant, more patients in Group II experienced graft loss, 25/100 vs. 18/100 in Group I(P=0.23). Actuarial patient/graft survival at 96mo was 92%/83% vs. 85%/73% in Groups I and II(N.S.). DWFG-due-to-infection(N.S.), EC-MPS withholding-due-to-leukopenia during the first 2mo(P=0.03), and incidence of viral infections(P=0.09) were higher in Group II, whereas EC-MPS withholding-due-to-GI symptoms was higher in Group I(P=0.009). No other adverse event differences were observed. While long-term anti-rejection and renal function efficacy were demonstrated in both treatment arms, slight over-immunosuppression of Group II patients occurred.
authors.affiliation: The Lillian Jean Kaplan Renal Transplant Center and the Miami Transplant Institute, Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address: gciancio@med.miami.edu.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Ciancio
authors.affiliation: The Lillian Jean Kaplan Renal Transplant Center and the Miami Transplant Institute, Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address: jgaynor@med.miami.edu.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Gaynor
authors.affiliation: Division of Nephrology of the Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address: gguerra@med.miami.edu.
authors.forename: Giselle
authors.initials: G
authors.lastname: Guerra
authors.affiliation: The Lillian Jean Kaplan Renal Transplant Center and the Miami Transplant Institute, Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address: jsageshima@ucdavis.edu.
authors.forename: Junichiro
authors.initials: J
authors.lastname: Sageshima
authors.affiliation: Division of Nephrology of the Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address: droth@med.miami.edu.
authors.forename: David
authors.initials: D
authors.lastname: Roth
authors.affiliation: The Lillian Jean Kaplan Renal Transplant Center and the Miami Transplant Institute, Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address: ljchen@med.miami.edu.
authors.forename: Linda
authors.initials: L
authors.lastname: Chen
authors.affiliation: Division of Nephrology of the Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address: wkupin@med.miami.edu.
authors.forename: Warren
authors.initials: W
authors.lastname: Kupin
authors.affiliation: Division of Nephrology of the Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address: amattiazzi@med.miami.edu.
authors.forename: Adela
authors.initials: A
authors.lastname: Mattiazzi
authors.affiliation: The Lillian Jean Kaplan Renal Transplant Center and the Miami Transplant Institute, Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address: ltueros@med.miami.edu.
authors.forename: Lissett
authors.initials: L
authors.lastname: Tueros
authors.affiliation: The Lillian Jean Kaplan Renal Transplant Center and the Miami Transplant Institute, Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address: sflores@med.miami.edu.
authors.forename: Sandra
authors.initials: S
authors.lastname: Flores
authors.affiliation: The Lillian Jean Kaplan Renal Transplant Center and the Miami Transplant Institute, Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address: h_lois@bellsouth.net.
authors.forename: Lois
authors.initials: L
authors.lastname: Hanson
authors.affiliation: The Lillian Jean Kaplan Renal Transplant Center and the Miami Transplant Institute, Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Phillip
authors.initials: P
authors.lastname: Ruiz
authors.affiliation: The Lillian Jean Kaplan Renal Transplant Center and the Miami Transplant Institute, Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address: r.vianna@med.miami.edu.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Vianna
authors.affiliation: The Lillian Jean Kaplan Renal Transplant Center and the Miami Transplant Institute, Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address: gburke@med.miami.edu.
authors.forename: George W
authors.initials: GW
authors.lastname: Burke
mesh_terms: D000074323:Alemtuzumab / Q000627:therapeutic use*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D000077561:Daclizumab; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000188:drug therapy* / Q000401:mortality; D006085:Graft Survival; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000009:adverse effects; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011817:Rabbits; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000961:Antilymphocyte Serum; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D000074323:Alemtuzumab; D000077561:Daclizumab
keywords: Alemtuzumab; Biopsy-proven acute rejection; Daclizumab; Enteric-coated mycophenolate sodium; Graft survival; Rabbit antithymocyte globulin; Renal transplantation; Steroid avoidance; Tacrolimus