Journal ArticleDOI
Reduction of acute renal allograft rejection by daclizumab. Daclizumab Double Therapy Study Group.
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TLDR
Administration of daclizumab in addition to dual immunosuppression therapy significantly reduced biopsy-proven acute rejection after renal transplantation, improved patient survival, and did not add to the toxicity of the immunOSuppressive regimen.Abstract:
Background Acute rejection is still a major problem in renal transplantation and is one of the most important causes of chronic graft dysfunction and late graft loss. Selective immunosuppression with a humanized antibody against the alpha-chain of the interleukin (IL)-2 receptor (CD25) was evaluated to demonstrate the efficacy of this type of immunoprophylaxis in combination with dual immunosuppression. Methods We studied the effect of daclizumab, a humanized monoclonal antibody against the alpha-chain of the IL-2 receptor, in a randomized double-blind, prospective phase III clinical trial in 275 patients receiving a first cadaveric renal allograft. Among them 111 (83%) in the placebo arm and 116 (82%) in the daclizumab arm received the full regimen of five doses (1.0 mg/kg) every other week. Baseline immunosuppression consisted of cyclosporine and corticosteroids. Results At 6 months, 39 (28%) of the patients in the daclizumab group had biopsy-proven rejections, as compared with 63 (47%) in the placebo group (P=0.001). The need for additional antilymphocyte therapy, antithymocyte globulin, antilymphocyte globulin (ATG, ALG, OKT3) was also lower in the daclizumab group (8% vs. 16%, P=0.02), and they required significantly lower mean (+/- SD) cumulative doses of prednisone (3750+/-1981 mg vs. 4438+/-2667 mg in the placebo group, P=0.01). Graft function was significantly better (P=0.02) in the daclizumab group (graft function rate: 58 vs. 51 ml/min, mean) as was patient survival (P=0.01, 99% vs. 94%). No specific adverse events were observed in daclizumab-treated patients. Patients receiving daclizumab experienced fewer cytomegalovirus infections (18% vs. 25%), and none died from severe infectious complications, compared to four patients in the placebo arm. No patient in the daclizumab group had a lymphoproliferative disorder or any other form of immunosuppression-related tumor during the first year after transplant. Conclusions Administration of daclizumab in addition to dual immunosuppression therapy significantly reduced biopsy-proven acute rejection after renal transplantation, improved patient survival, and did not add to the toxicity of the immunosuppressive regimen.read more
Citations
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Immunosuppressive Drugs for Kidney Transplantation
TL;DR: This review considers the use of immunosuppressive drugs in organ transplantation, focusing on renal transplantation.
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Antibody engineering via genetic engineering of the mouse: XenoMouse strains are a vehicle for the facile generation of therapeutic human monoclonal antibodies.
TL;DR: The utility of XenoMouse strains for the generation of large panels of high-affinity, fully human mAbs can be made available to researchers in the academic and private sectors, and should accelerate the development and application of mAbs as therapeutics for human disease.
Journal ArticleDOI
Mycophenolate mofetil reduces late renal allograft loss independent of acute rejection.
Akinlolu O. Ojo,Herwig Ulf Meier-Kriesche,Julie A. Hanson,Alan B. Leichtman,Diane M. Cibrik,John C. Magee,Robert A. Wolfe,Lawrence Y. Agodoa,Bruce Kaplan +8 more
TL;DR: Mycophenolate Mofetil therapy decreased the relative risk for development of chronic allograft failure (CAF) by 27% and was independent of its outcome on acute rejection.
Journal ArticleDOI
Identification of Therapeutic Targets for Quiescent, Chemotherapy-Resistant Human Leukemia Stem Cells
Yoriko Saito,Hiroshi Kitamura,Atsushi Hijikata,Mariko Tomizawa-Murasawa,Satoshi Tanaka,Shinsuke Takagi,Naoyuki Uchida,Nahoko Suzuki,Akiko Sone,Yuho Najima,Hidetoshi Ozawa,Atsushi Wake,Shuichi Taniguchi,Leonard D. Shultz,Osamu Ohara,Fumihiko Ishikawa +15 more
TL;DR: In this paper, the authors identify a primary human LSC gene signature and functional characterization of LSC-specific molecules in vivo in a mouse xenotransplantation model and demonstrate that CD32 and CD25-positive LSCs could initiate acute myeloid leukemia and were cell cycle-quiescent and chemotherapy-resistant in vivo.
Journal ArticleDOI
Immunosuppressive agents in solid organ transplantation: Mechanisms of action and therapeutic efficacy.
TL;DR: An overview of the different immunosuppressive agents currently used in solid organ transplantation is provided and many of the key clinical trials that underpin current clinical usage of these agents are described and side-effects are highlighted.
References
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Journal ArticleDOI
A humanized antibody that binds to the interleukin 2 receptor.
Cary L. Queen,William P. Schneider,Harold E. Selick,Philip W. Payne,Nicholas F. Landolfi,James F. Duncan,Nevenka M. Avdalovic,Michael Levitt,Richard P. Junghans,Thomas A. Waldmann +9 more
TL;DR: A "humanized" antibody is constructed by combining the complementarity-determining regions (CDRs) of the anti-Tac antibody with human framework and constant regions and has an affinity for p55 of 3 x 10(9) M-1, about 1/3 that of murine anti- Tac.
Journal ArticleDOI
Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric renal allograft recipients. U.S. Renal Transplant Mycophenolate Mofetil Study Group.
TL;DR: This study demonstrated that MMF administered at a dosage of 2 g or 3 g daily, in combination with maintenance CsA and corticosteroids as triple therapy following ATGAM® induction therapy, is more effective than an otherwise identical regimen that includes azathioprine instead of MMF in preventing acute allograft rejection in first cadaveric renal transplant patients.
Journal Article
Placebo-controlled study of mycophenolate mofetil combined with cyclosporine and corticosteroids for prevention of acute rejection
Josep M. Grinyó,Carl-Gustav Groth,Rudolf Pichlmayr,Sa Sadek,Yves Vanrenterghem,M Behrend,R Luck,Francesc Moreso,J Peeters,J Rodicio,J Morales,Dagfinn Albrechtsen,P Fauchald,Sameh S. Sadek,J. P. A. Lodge,Jp Soulillou,Diego Cantarovich,van Willem Son,Adam Tegzess,Karl-Heinz Wagner,J Erhard,Christina Brattström,Lars Mjörnstedt,M. Wiesel,S. Carl,Hh Neumayer,Hauser,Peter Lang,B Bourgeon,Gunnar Tufveson,G. Gannedahl,Henrik Ekberg,N. Persson,A Tarantino,M Campise,G Thiel,M Zeiler,R Hene,G Ligtenberg,A Morgan,K Rigg,Hooftman L,K Hutchinson +42 more
TL;DR: MMF significantly reduced the rate of biopsy-proven rejection or other treatment failure during the first 6 months after transplantation and was well tolerated, although the 3 g dose was somewhat less well tolerated.
Journal ArticleDOI
A blinded, randomized clinical trial of mycophenolate mofetil for the prevention of acute rejection in cadaveric renal transplantation
Paul Keown,Pekka Häyry,Peter J. Morris,Calvin R. Stiller,Christopher M. Barker,Lisa Carr,David Landsberg,Ian R. Hardie,Russell J. Rigby,Helena Isoniemi,Derek W. R. Gray,Philip Belitsky,Allan McDonald,Tim Mathew,A. Clarkson,L. Barratt,B. Buchholz,Rowan Walker,Günther Kirste,Norman Muirhead,David J. Tiller,Geoff Duggin,Philip F. Halloran,Pierre Daloze,Gilles St. Louis,David Russell,David Ludwin,P. Vialtel,U. Binswanger,J. A C Buckels,Jean Louis Touraine,David P. Hickey,Giuseppe Remuzzi,Giuseppe Locatelli,F. T. Lam,Ed Tapper +35 more
TL;DR: MMF is associated with a significantly lower rate of treatment failure compared with AZA during the first 6 months after renal transplantation and produces a clinically important reduction in the incidence, severity, and treatment of acute graft rejection.
Journal ArticleDOI
Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection - A report of the European Tacrolimus Multicenter Renal Study Group
AD Mayer,Jean-Paul Squifflet +1 more
TL;DR: A significant reduction in the incidence of episodes of allograft rejection observed with tacrolimus therapy may have important long-term implications given the prognostic influence of rejection on graft survival.