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Published in: Drugs 12/2006

01-08-2006 | Leading Article

Immunosuppressive Preconditioning or Induction Regimens

Evidence to Date

Authors: Dr Henkie P. Tan, Marc C. Smaldone, Ron Shapiro

Published in: Drugs | Issue 12/2006

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Abstract

The success of solid organ transplantation has been directly related to the development of immunosuppressive drug therapies. Preconditioning or induction therapy was developed to reduce early immunological and nonimmunological renal injury, with the goal of increasing long-term graft survival. However, the routine induction of immunological tolerance to solid organ allograft is currently not achievable because of the morbidity and mortality related to the immunosuppressive regimens themselves. The different therapeutic preconditioning or induction agents and their associated effects on cellular rejection, graft survival outcomes and the need for multiagent post-transplant maintenance therapy are reviewed.
Footnotes
1
The use of trade names is for product identification purposes only and does not imply endorsement.
 
Literature
1.
Bunnapradist S, Takemoto SK. Multivariate analyses of antibody induction therapies. Clin Transpl 2003: 405–17
2.
Monaco AP. Immunosuppression and tolerance for clinical organ allografts. Curr Opin Immunol 1989; 1(6): 1174–7PubMedCrossRef
3.
Levey AS, Schmid CH, Lau J. Antilymphocyte antibodies, renal transplantation, and meta-analysis. Ann Intern Med 1998; 128(10): 863–5PubMed
4.
Halloran PF. Immunosuppressive drugs for kidney transplantation. N Engl J Med 2004; 351(26): 2715–29PubMedCrossRef
5.
Starzl TE, Marchioro TL, Porter KA, et al. The use of heterologous antilymphoid agents in canine renal and liver homotransplantation and in human renal homotransplantation. Surg Gynecol Obstet 1967; 124(2): 301–8PubMed
6.
Gaber AO, First MR, Tesi RJ, et al. Results of the double-blind, randomized, multicenter, phase III clinical trial of thymoglobulin versus atgam in the treatment of acute graft rejection episodes after renal transplantation. Transplantation 1998; 66(1): 29–37PubMedCrossRef
7.
Brennan DC, Flavin K, Lowell JA, et al. A randomized, double-blinded comparison of thymoglobulin versus atgam for induction immunosuppressive therapy in adult renal transplant recipients. Transplantation 1999; 67(7): 1011–8PubMedCrossRef
8.
Kuypers DR, Vanrenterghem YF. Monoclonal antibodies in renal transplantation: old and new. Nephrol Dial Transplant 2004; 19(2): 297–300PubMedCrossRef
9.
Opelz G, Dohler B. Lymphomas after solid organ transplantation: a collaborative transplant study report. Am J Transplant 2004; 4(2): 222–30PubMedCrossRef
10.
Cyclosporine monotherapy versus OKT3 and cyclosporine versus prednisone and cyclosporine as induction therapy in older renal transplant patients: a multicenter randomized study. Spanish Monotherapy Study Group. Transplant Proc 1994; 26(5): 2522–4
11.
Belitsky P, MacDonald AS, Cohen AD, et al. Comparison of antilymphocyte globulin and continuous i.v. cyclosporine A as induction immunosuppression for cadaver kidney transplants: a prospective randomized study. Transplant Proc 1991; 23 (1 Pt 2): 999–1000PubMed
12.
Banhegyi C, Rockenschaub S, Muhlbacher F, et al. Preliminary results of a prospective randomized clinical trial comparing cyclosporine A to antithymocyte globulin immunosuppressive induction therapy in kidney transplantation. Transplant Proc 1991; 23(4): 2207–8PubMed
13.
Abramowicz D, Goldman M, De Pauw L, et al. The long-term effects of prophylactic OKT3 monoclonal antibody in cadaver kidney transplantation: a single-center, prospective, randomized study. Transplantation 1992; 54(3): 433–7PubMedCrossRef
14.
Norman DJ, Kahana L, Stuart FP, et al. A randomized clinical trial of induction therapy with OKT3 in kidney transplantation. Transplantation 1993; 55(1): 44–50PubMedCrossRef
15.
Slakey DP, Johnson CP, Callaluce RD, et al. A prospective randomized comparison of quadruple versus triple therapy for first cadaver transplants with immediate function. Transplantation 1993; 56(4): 827–31PubMedCrossRef
16.
Szczech LA, Berlin JA, Feldman HI. The effect of antilymphocyte induction therapy on renal allograft survival: a meta-analysis of individual patient-level data. Anti-Lymphocyte Antibody Induction Therapy Study Group. Ann Intern Med 1998; 128(10): 817–26
17.
Charpentier B, Rostaing L, Berthoux F, et al. A three-arm study comparing immediate tacrolimus therapy with antithymocyte globulin induction therapy followed by tacrolimus or cyclosporine A in adult renal transplant recipients. Transplantation 2003; 75(6): 844–51PubMedCrossRef
18.
Swanson SJ, Hale DA, Mannon RB, et al. Kidney transplantation with rabbit antithymocyte globulin induction and sirolimus monotherapy. Lancet 2002; 360(9346): 1662–4PubMedCrossRef
19.
Benfield MR, Tejani A, Harmon WE, et al. A randomized multicenter trial of OKT3 mAbs induction compared with intravenous cyclosporine in pediatric renal transplantation. Pediatr Transplant 2005; 9(3): 282–92PubMedCrossRef
20.
Shapiro R, Jordan ML, Basu A, et al. Kidney transplantation under a tolerogenic regimen of recipient pretreatment and low-dose postoperative immunosuppression with subsequent weaning. Ann Surg 2003; 238(4): 520–5PubMed
21.
Bogetti D, Sankary HN, Jarzembowski TM, et al. Thymoglobulin induction protects liver allografts from ischemia/reperfusion injury. Clin Transplant 2005; 19(4): 507–11PubMedCrossRef
22.
Eason JD, Nair S, Cohen AJ, et al. Steroid-free liver transplantation using rabbit antithymocyte globulin and early tacrolimus monotherapy. Transplantation 2003; 75(8): 1396–9PubMedCrossRef
23.
Opelz G. Efficacy of rejection prophylaxis with OKT3 in renal transplantation. Collaborative Transplant Study. Transplantation 1995; 60(11): 1220–4
24.
Cecka JM, Gjertson D, Terasaki PI. Do prophylactic antilymphocyte globulins (ALG and OKT3) improve renal transplant survival in recipient and donor high-risk groups? Transplant Proc 1993; 25 (1 Pt 1): 548–9PubMed
25.
Reyes J, Mazariegos GV, Abu-Elmagd K, et al. Intestinal transplantation under tacrolimus monotherapy after perioperative lymphoid depletion with rabbit anti-thymocyte globulin (thymoglobulin). Am J Transplant 2005; 5(6): 1430–6PubMedCrossRef
26.
Hale G, Dyer MJ, Clark MR, et al. Remission induction in non-Hodgkin lymphoma with reshaped human monoclonal antibody CAMPATH-1H. Lancet 1988; II(8625): 1394–9CrossRef
27.
Lundin J, Osterborg A, Brittinger G, et al. CAMPATH-1H monoclonal antibody in therapy for previously treated low-grade non-Hodgkin's lymphomas: a phase II multicenter study. European Study Group of CAMPATH-1H Treatment in Low-Grade Non-Hodgkin's Lymphoma. J Clin Oncol 1998; 16(10): 3257–63
28.
Calne R, Moffatt SD, Friend PJ, et al. Campath IH allows low-dose cyclosporine monotherapy in 31 cadaveric renal allograft recipients. Transplantation 1999; 68(10): 1613–6PubMedCrossRef
29.
Kaufman DB, Leventhal JR, Axelrod D, et al. Alemtuzumab induction and prednisone-free maintenance immunotherapy in kidney transplantation: comparison with basiliximab induction: long-term results. Am J Transplant 2005; 5(10): 2539–48PubMedCrossRef
30.
Shapiro R, Basu A, Tan H, et al. Kidney transplantation under minimal immunosuppression after pretransplant lymphoid depletion with thymoglobulin or campath. J Am Coll Surg 2005; 200(4): 505–15PubMedCrossRef
31.
Knechtle SJ, Pirsch JD, Fechner H, et al. Campath-1H induction plus rapamycin monotherapy for renal transplantation: results of a pilot study. Am J Transplant 2003; 3(6): 722–30PubMedCrossRef
32.
Ciancio G, Burke GW, Gaynor JJ, et al. The use of campath-1H as induction therapy in renal transplantation: preliminary results. Transplantation 2004; 78(3): 426–33PubMedCrossRef
33.
Flechner SM, Friend PJ, Brockmann J, et al. Alemtuzumab induction and sirolimus plus mycophenolate mofetil maintenance for CNI and steroid-free kidney transplant immunosuppression. Am J Transplant 2005; 5(12): 3009–14PubMedCrossRef
34.
Vathsala A, Ona ET, Tan SY, et al. Randomized trial of Alemtuzumab for prevention of graft rejection and preservation of renal function after kidney transplantation. Transplantation 2005; 80(6): 765–74PubMedCrossRef
35.
Watson CJ, Bradley JA, Friend PJ, et al. Alemtuzumab (CAMPATH 1H) induction therapy in cadaveric kidney transplantation: efficacy and safety at five years. Am J Transplant 2005; 5(6): 1347–53PubMedCrossRef
36.
Hale G, Waldmann H, Dyer M. Specificity of monoclonal antibody Campath-1. Bone Marrow Transplant 1988; 3(3): 237–9PubMed
37.
Kirk AD, Hale DA, Mannon RB, et al. Results from a human renal allograft tolerance trial evaluating the humanized CD52-specific monoclonal antibody alemtuzumab (CAMPATH-1H). Transplantation 2003; 76(1): 120–9PubMedCrossRef
38.
Kirk AD, Mannon RB, Kleiner DE, et al. Results from a human renal allograft tolerance trial evaluating T-cell depletion with alemtuzumab combined with deoxyspergualin. Transplantation 2005; 80(8): 1051–9PubMedCrossRef
39.
Knechtle SJ, Fernandez LA, Pirsch JD, et al. Campath-1H in renal transplantation: The University of Wisconsin experience. Surgery 2004; 136(4): 754–60PubMedCrossRef
40.
Tan HP, Kaczorowski D, Basu A, et al. Steroid-free tacrolimus monotherapy after pretransplantation thymoglobulin or campath and laparoscopy in living donor renal transplantation. Transplant Proc 2005; 37(10): 4235–40PubMedCrossRef
41.
Tan HP, Kaczorowski DJ, Basu A, et al. Living-related donor renal transplantation in HIV+ recipients using alemtuzumab preconditioning and steroid-free tacrolimus monotherapy: a single center preliminary experience. Transplantation 2004; 78(11): 1683–8PubMedCrossRef
42.
Shapiro R, Ellis D, Tan H. Antilymphoid antibody preconditioning and tacrolimus monotherapy for pediatric kidney transplantation. J Pediatr 2006 Jun; 148(6): 813–8PubMedCrossRef
43.
Bartosh SM, Knechtle SJ, Sollinger HW. Campath-1H use in pediatric renal transplantation. Am J Transplant 2005; 5(6): 1569–73PubMedCrossRef
44.
Gruessner RW, Kandaswamy R, Humar A, et al. Calcineurin inhibitor- and steroid-free immunosuppression in pancreas-kidney and solitary pancreas transplantation. Transplantation 2005; 79(9): 1184–9PubMedCrossRef
45.
Thai NL, Abu-Elmagd K, Khan A, et al. Pancreatic transplantation at the University of Pittsburgh. Clin Transpl 2004: 205–14
46.
Tryphonopoulos P, Madariaga JR, Kato T, et al. The impact of Campath 1H induction in adult liver allotransplantation. Transplant Proc 2005; 37(2): 1203–4PubMedCrossRef
47.
Tzakis AG, Tryphonopoulos P, Kato T, et al. Preliminary experience with alemtuzumab (Campath-1H) and low-dose tacrolimus immunosuppression in adult liver transplantation. Transplantation 2004; 77(8): 1209–14PubMedCrossRef
48.
Tzakis AG, Kato T, Nishida S, et al. Alemtuzumab (campath-1H) combined with tacrolimus in intestinal and multivisceral transplantation. Transplantation 2003; 75(9): 1512–7PubMedCrossRef
49.
Marcos A, Eghtesad B, Fung JJ, et al. Use of alemtuzumab and tacrolimus monotherapy for cadaveric liver transplantation: with particular reference to hepatitis C virus. Transplantation 2004; 78(7): 966–71PubMedCrossRef
50.
McCurry KR, Iacono A, Zeevi A, et al. Early outcomes in human lung transplantation with thymoglobulin or campath-1H for recipient pretreatment followed by posttransplant tacrolimus near-monotherapy. J Thorac Cardiovasc Surg 2005; 130(2): 528–37PubMedCrossRef
51.
Basu A, Ramkumar M, Tan HP, et al. Reversal of acute cellular rejection after renal transplantation with campath-1H. Transplant Proc 2005; 37(2): 923–6PubMedCrossRef
52.
Tan HP, Kaczorowski DJ, Basu A, et al. Living donor renal transplantation using alemtuzumab induction and tacrolimus monotherapy. Am J Transplant. In press
53.
Silveira FP, Marcos A, Kwak EJ, et al. Bloodstream infections in organ transplant recipients receiving alemtuzumab: no evidence of occurrence of organisms typically associated with profound T cell depletion. J Infect. Epub 2006 Jan 2
54.
Anderson DR, Grillo-Lopez A, Varns C, et al. Targeted anti-cancer therapy using rituximab, a chimaeric anti-CD20 antibody (IDEC-C2B8) in the treatment of non-Hodgkin's B-cell lymphoma. Biochem Soc Trans 1997; 25(2): 705–8PubMed
55.
Becker YT, Becker BN, Pirsch JD, et al. Rituximab as treatment for refractory kidney transplant rejection. Am J Transplant 2004; 4(6): 996–1001PubMedCrossRef
56.
Tyden G, Kumlien G, Fehrman I. Successful ABO-incompatible kidney transplantations without splenectomy using antigen-specific immunoadsorption and rituximab. Transplantation 2003; 76(4): 730–1PubMedCrossRef
57.
Sawada T, Fuchinoue S, Teraoka S. Successful A1-to-O ABO-incompatible kidney transplantation after a preconditioning regimen consisting of anti-CD20 monoclonal antibody infusions, splenectomy, and double-filtration plasmapheresis. Transplantation 2002; 74(9): 1207–10PubMedCrossRef
58.
Jain AB, Marcos A, Pokharna R, et al. Rituximab (chimeric anti-cd20 antibody) for posttransplant lymphoproliferative disorder after solid organ transplantation in adults: long-term experience from a single center. Transplantation 2005; 80(12): 1692–8PubMedCrossRef
59.
Sawada T, Fuchinoue S, Kawase T, et al. Preconditioning regimen consisting of anti-CD20 monoclonal antibody infusions, splenectomy and DFPP-enabled non-responders to undergo ABO-incompatible kidney transplantation. Clin Transplant 2004; 18(3): 254–60PubMedCrossRef
60.
Gloor JM, DeGoey SR, Pineda AA, et al. Overcoming a positive crossmatch in living-donor kidney transplantation. Am J Transplant 2003; 3(8): 1017–23PubMedCrossRef
61.
Chapman TM, Keating GM. Basiliximab: a review of its use as induction therapy in renal transplantation. Drugs 2003; 63(24): 2803–35PubMedCrossRef
62.
Vincenti F, Kirkman R, Light S, et al. Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation. Daclizumab Triple Therapy Study Group. N Engl J Med 1998; 338(3): 161–5CrossRef
63.
Light JA, Sasaki TM, Ghasemian R, et al. Daclizumab induction/tacrolimus sparing: a randomized prospective trial in renal transplantation. Clin Transplant 2002; 16 Suppl. 7: 30–3PubMedCrossRef
64.
Kahan BD, Rajagopalan PR, Hall M. Reduction of the occurrence of acute cellular rejection among renal allograft recipients treated with basiliximab, a chimeric anti-interleukin-2-receptor monoclonal antibody. United States Simulect Renal Study Group. Transplantation 1999; 67(2): 276–84
65.
Vincenti F, Nashan B, Light S. Daclizumab: outcome of phase III trials and mechanism of action: double therapy and the triple therapy study groups. Transplant Proc 1998; 30(5): 2155–8PubMedCrossRef
66.
Lawen JG, Davies EA, Mourad G, et al. Randomized double-blind study of immunoprophylaxis with basiliximab, a chimeric anti-interleukin-2 receptor monoclonal antibody, in combination with mycophenolate mofetil-containing triple therapy in renal transplantation. Transplantation 2003; 75(1): 37–43PubMedCrossRef
67.
Ponticelli C, Yussim A, Cambi V, et al. A randomized, double-blind trial of basiliximab immunoprophylaxis plus triple therapy in kidney transplant recipients. Transplantation 2001; 72(7): 1261–7PubMedCrossRef
68.
Nashan B, Moore R, Amlot P, et al. Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients. CHIB 201 International Study Group. Lancet 1997; 350(9086): 1193–8
69.
Sheashaa HA, Bakr MA, Ismail AM, et al. Basiliximab reduces the incidence of acute cellular rejection in live-related-donor kidney transplantation: a three-year prospective randomized trial. J Nephrol 2003; 16(3): 393–8PubMed
70.
Ekberg H, Backman L, Tufveson G, et al. Daclizumab prevents acute rejection and improves patient survival post transplantation: 1 year pooled analysis. Transpl Int 2000; 13(2): 151–9PubMedCrossRef
71.
Lebranchu Y, Bridoux F, Buchler M, et al. Immunoprophylaxis with basiliximab compared with antithymocyte globulin in renal transplant patients receiving MMF-containing triple therapy. Am J Transplant 2002; 2(1): 48–56PubMedCrossRef
72.
Pham K, Kraft K, Thielke J, et al. Limited-dose daclizumab versus basiliximab: a comparison of cost and efficacy in preventing acute rejection. Transplant Proc 2005; 37(2): 899–902PubMedCrossRef
73.
Nair MP, Nampoory MR, Johny KV, et al. Induction immunosuppression with interleukin-2 receptor antibodies (basiliximab and daclizumab) in renal transplant recipients. Transplant Proc 2001; 33(5): 2767–9PubMedCrossRef
74.
Keown P, Balshaw R, Khorasheh S, et al. Meta-analysis of basiliximab for immunoprophylaxis in renal transplantation. BioDrugs 2003; 17(4): 271–9PubMedCrossRef
75.
Adu D, Cockwell P, Ives NJ, et al. Interleukin-2 receptor monoclonal antibodies in renal transplantation: meta-analysis of randomised trials. BMJ 2003; 326(7393): 789PubMedCrossRef
76.
Webster AC, Playford EG, Higgins G, et al. Interleukin 2 receptor antagonists for renal transplant recipients: a meta-analysis of randomized trials. Transplantation 2004; 77(2): 166–76PubMedCrossRef
77.
Kuypers DR, Evenepoel P, Maes B, et al. The use of an anti-CD25 monoclonal antibody and mycophenolate mofetil enables the use of a low-dose tacrolimus and early withdrawal of steroids in renal transplant recipients. Clin Transplant 2003; 17(3): 234–41PubMedCrossRef
78.
Vincenti F, Ramos E, Brattstrom C, et al. Multicenter trial exploring calcineurin inhibitors avoidance in renal transplantation. Transplantation 2001; 71(9): 1282–7PubMedCrossRef
79.
von Willebrand E, Lautenschlager I, Krogerus L, et al. Adhesion molecules and activation markers in acute rejection of human renal allografts. Transpl Immunol 1996; 4(1): 57–8CrossRef
80.
Cosimi AB, Conti D, Delmonico FL, et al. In vivo effects of monoclonal antibody to ICAM-1 (CD54) in nonhuman primates with renal allografts. J Immunol 1990; 144(12): 4604–12PubMed
81.
Salmela K, Wramner L, Ekberg H, et al. A randomized multicenter trial of the anti-ICAM-1 monoclonal antibody (enlimomab) for the prevention of acute rejection and delayed onset of graft function in cadaveric renal transplantation: a report of the European Anti-ICAM-1 Renal Transplant Study Group. Transplantation 1999; 67(5): 729–36PubMedCrossRef
82.
Huang X, Shen W, Li Y, et al. Expression of ICAM-1 and LFA-1 molecules in relation to renal allograft rejection in rats. Chin Med Sci J 1999; 14(3): 163–6PubMed
83.
Hourmant M, Bedrossian J, Durand D, et al. A randomized multicenter trial comparing leukocyte function-associated antigen-1 monoclonal antibody with rabbit antithymocyte globulin as induction treatment in first kidney transplantations. Transplantation 1996; 62(11): 1565–70PubMedCrossRef
84.
Isobe M, Yagita H, Okumura K, et al. Specific acceptance of cardiac allograft after treatment with antibodies to ICAM-1 and LFA-1. Science 1992; 255(5048): 1125–7PubMedCrossRef
85.
Starzl TE, Demetris AJ, Trucco M, et al. Cell migration and chimerism after whole-organ transplantation: the basis of graft acceptance. Hepatology 1993; 17(6): 1127–52PubMedCrossRef
86.
Starzl TE, Demetris AJ, Trucco M, et al. Systemic chimerism in human female recipients of male livers. Lancet 1992; 340(8824): 876–7PubMedCrossRef
87.
Starzl TE, Zinkernagel RM. Antigen localization and migration in immunity and tolerance. N Engl J Med 1998; 339(26): 1905–13PubMedCrossRef
88.
Starzl TE, Zinkernagel RM. Transplantation tolerance from a historical perspective. Nat Rev Immunol 2001; 1(3): 233–9PubMedCrossRef
Metadata
Title
Immunosuppressive Preconditioning or Induction Regimens
Evidence to Date
Authors
Dr Henkie P. Tan
Marc C. Smaldone
Ron Shapiro
Publication date
01-08-2006
Publisher
Springer International Publishing
Published in
Drugs / Issue 12/2006
Print ISSN: 0012-6667
Electronic ISSN: 1179-1950
DOI
https://doi.org/10.2165/00003495-200666120-00001

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