New developments in immunosuppressive therapy for heart transplantation

Expert Opinion on Emerging Drugs

Volumn 14, Issue 1, 2009, Pages 1-21

  Khush, Kiran K ^a   Valantine, Hannah A ^a  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Acute rejection; AEB071; Alefacept; Alemtuzumab; Antibody mediated rejection; Antiproliferative agents; Antithymocyte globulin; Atacicept; Azathioprine; Basiliximab; Belatacept; Belimumab; Bortezomib; Calcineurin inhibitor; Cardiac allograft vasculopathy; Cellular rejection; Chronic rejection; Ciclosporin; Corticosteroids; CP 690550; Daclizumab; Efalizumab; Epratuzumab; Everolimus; FK778; FTY720; Heart transplant; Immunosuppressant drugs; Induction regimen; ISA247; JAK 3 inhibitor; KRP203; Monoclonal antibodies; Muromonab; Mycophenolate mofetil; OKT3; Polyclonal antibodies; Proliferation signal inhibitors; Rapamycin; Sirolimus; Tacrolimus; Voclosporin

Indexed keywords

ALEMTUZUMAB; AZATHIOPRINE; BASILIXIMAB; CALCINEURIN INHIBITOR; CALCIUM CHANNEL BLOCKING AGENT; CORTICOSTEROID; CYCLOSPORIN; CYCLOSPORIN A; DACLIZUMAB; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; EVEROLIMUS; FINGOLIMOD; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; IMMUNOGLOBULIN; INTERLEUKIN 10; JANUS KINASE 3 INHIBITOR; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; METHOTREXATE; METHYLPREDNISOLONE; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; OKT 3; PLACEBO; PRAVASTATIN; PREDNISONE; RAPAMYCIN; RITUXIMAB; SIMVASTATIN; TACROLIMUS; THYMOCYTE ANTIBODY; UNINDEXED DRUG; IMMUNOSUPPRESSIVE AGENT;

ACNE; ACUTE GRAFT REJECTION; ADD ON THERAPY; ALOPECIA; ANAPHYLAXIS; ANTIBODY MEDIATED REJECTION; BONE MARROW SUPPRESSION; BRADYCARDIA; BRONCHIOLITIS OBLITERANS; CARDIAC ALLOGRAFT VASCULOPATHY; CATARACT; CELL THERAPY; CHILL; CHRONIC DIARRHEA; CHRONIC GRAFT REJECTION; CLINICAL TRIAL; CORONARY ARTERY DILATATION; CUSHING SYNDROME; CYTOMEGALOVIRUS INFECTION; DIABETES MELLITUS; DIARRHEA; DIGESTIVE SYSTEM ULCER; DRUG BIOAVAILABILITY; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG FATALITY; DRUG FORMULATION; DRUG MECHANISM; DRUG MEGADOSE; DRUG RECEPTOR BINDING; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSPEPSIA; FEVER; FLU LIKE SYNDROME; GASTRITIS; GASTROINTESTINAL REFLUX; GINGIVA HYPERPLASIA; GRAFT FAILURE; GRAFT REJECTION; GRAFT SURVIVAL; HEART ARRHYTHMIA; HEART DISEASE; HEART FAILURE; HEART TRANSPLANTATION; HEMOLYTIC UREMIC SYNDROME; HIRSUTISM; HUMAN; HYPERGLYCEMIA; HYPERLIPIDEMIA; HYPERTENSION; HYPOTENSION; IMMUNOSUPPRESSIVE TREATMENT; INFECTION SENSITIVITY; INSULIN RESISTANCE; KIDNEY DYSFUNCTION; LEUKOPENIA; LUNG DISEASE; LUNG EDEMA; LYMPHOMA; MAXIMUM PLASMA CONCENTRATION; MEDLINE; MORTALITY; MOUTH ULCER; MYOPATHY; NEPHROTOXICITY; NEUROTOXICITY; NONHUMAN; OBESITY; OPPORTUNISTIC INFECTION; OSTEOPOROSIS; PERICARDIAL EFFUSION; PERIPHERAL EDEMA; PLASMAPHERESIS; PLEURA EFFUSION; PNEUMONIA; RETINA MACULA EDEMA; REVIEW; RISK REDUCTION; SERUM SICKNESS; SHOCK; SIDE EFFECT; SYSTEMATIC REVIEW; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; THROMBOCYTOPENIA; TUBERCULOSIS; VIRUS INFECTION; WEIGHT GAIN; WOUND HEALING IMPAIRMENT; ANIMAL; DRUG DELIVERY SYSTEM; DRUG DESIGN;

ANIMALS; CLINICAL TRIALS AS TOPIC; DRUG DELIVERY SYSTEMS; DRUG DESIGN; GRAFT REJECTION; HEART DISEASES; HEART TRANSPLANTATION; HUMANS; IMMUNOSUPPRESSIVE AGENTS;

EID: 65649084468     PISSN: 14728214     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728210902791605     Document Type: Review

References (157)

1. Barnard CN. The operation. A human cardiac transplant: an interim report of a successful operation performed at Groote Schuur Hospital, Cape Town. S Afr Med J 1967;41(48):1271-1274
2. Taylor DO, Edwards LB, Aurora P, et al. Registry of the International Society for Heart and Lung Transplantation: twenty-fifth official adult heart transplant report, 2008. J Heart Lung Transplant 2008;27(9):943-56 • Comprehensive presentation of recent heart transplant statistics, including transplant volumes, morbidity, mortality, and immunosuppressive strategies.
3. Eisen HJ. Immunosuppression on the horizon. Heart Fail Clin 2007;3(1):43-49 (Pubitemid 46830078)
4. Hirose R, Vincenti F. Immunosuppression: today, tomorrow, and withdrawal. Semin Liver Dis 2006;26(3):201-210 (Pubitemid 44141927)
5. Vincenti F. What's in the pipeline? New immunosuppressive drugs in transplantation. Am J Transplant 2002;2(10):898-903 (Pubitemid 36330218)
6. Mankidy B, Kesavan RB, Silay YS, et al. Emerging drugs in lung transplantation. Expert Opin Emerg Drugs 2007;12(1):61-73 (Pubitemid 46499495)
7. Bonnefoy-Berard N, Revillard JP. Mechanisms of immunosuppression induced by antithymocyte globulins and OKT3. J Heart Lung Transplant 1996;15(5):435-442 (Pubitemid 26171239)
8. Chien NC, Lin FL, Chou NK, et al. Rabbit antithymocyte globulin induction immunosuppression in heart transplantation. Transplant Proc 2000;32(7):2380-2382
9. Lavee J, Bar-Zohar D, Har-Zahav Y, et al. Immunosuppression induction with rabbit antithymocyte globulin in heart transplantation patients: 6-year experience at the Sheba Medical Center. Transplant Proc 2000;32(4):737-739 (Pubitemid 30336718)
10. Di Filippo S, Boissonnat P, Sassolas F, et al. Rabbit antithymocyte globulin as induction immunotherapy in pediatric heart transplantation. Transplantation 2003;75(3):354-358 (Pubitemid 36222962)
11. Goland S, Czer LS, Coleman B, et al. Induction therapy with thymoglobulin after heart transplantation: impact of therapy duration on lymphocyte depletion and recovery, rejection, and cytomegalovirus infection rates. J Heart Lung Transplant 2008;27(10):1115-1121
12. Starnes VA, Oyer PE, Stinson EB, et al. Prophylactic OKT3 used as induction therapy for heart transplantation. Circulation 1989;80(5 Pt 2):III79-83 (Pubitemid 19280437)
13. Barr ML, Sanchez JA, Seche LA, et al. Anti-CD3 monoclonal antibody induction therapy. Immunological equivalency with triple-drug therapy in heart transplantation. Circulation 1990;82(5 Suppl):IV291-4
14. Van Gelder T, Daane CR, Vaessen LM, et al. In vitro and in vivo effects of BT 563, an anti-interleukin-2 receptor monoclonal antibody. Transpl Int 1994;7(Suppl 1):S556-8
15. Available from: www.clinicaltrials.gov [Cited 2 October 2008 ]
16. 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):120-129 (Pubitemid 36877125)
17. 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 2006;53(4):241-247
18. Knechtle SJ, Fernandez LA, Pirsch JD, et al. Campath-1H in renal transplantation: The University of Wisconsin experience. Surgery 2004;136(4):754-760 (Pubitemid 39311300)
19. 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):1347-1353 (Pubitemid 40839424)
20. Knechtle SJ, Pirsch JDH, Fechner JJ, et al. Campath-1H induction plus rapamycin monotherapy for renal transplantation: results of a pilot study. Am J Transplant 2003;3(6):722-730 (Pubitemid 36745245)
21. 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):765-774 (Pubitemid 41443758)
22. Pham SM, Jimenez J, Bednar BM. Campath in clinical heart transplantation. J Heart Lung Transplant 2006;25:S126
23. Kaufman DB, Leventhal JR, Gallon LG, Parker MA. Alemtuzumab induction and prednisone-free maintenance immunotherapy in simultaneous pancreaskidney transplantation comparison with rabbit antithymocyte globulin induction: long-term results. Am J Transplant 2006;6(2):331-339 (Pubitemid 43382168)
24. Lenihan DJ, Alencar AJ, Yang D, et al. Cardiac toxicity of alemtuzumab in patients with mycosis fungoides/sezary syndrome. Blood 2004;104(3):655-658 (Pubitemid 38970557)
25. Segovia J, Rodriguez-Lambert JL, Crespo-Leiro MG, et al. A randomized multicenter comparison of basiliximab and muromonab (OKT3) in heart transplantation: SIMCOR study. Transplantation 2006;81(11):1542-1548 (Pubitemid 43890891)
26. Mehra MR, Zucker MJ, Wagoner L, et al. A multicenter, prospective, randomized, double-blind trial of basiliximab in heart transplantation. J Heart Lung Transplant 2005;24(9):1297-1304 (Pubitemid 41247813)
27. Hershberger RE, Starling RC, Eisen HJ, et al. Daclizumab to prevent rejection after cardiac transplantation. N Engl J Med 2005;352(26):2705-13 • Multicenter clinical trial demonstrating efficacy of anti IL-2 receptor antibodies for induction therapy after heart transplantation.
28. Opelz G, Dohler B. Lymphomas after solid organ transplantation: a collaborative transplant study report. Am J Transplant 2004;4(2):222-230 (Pubitemid 38248525)
29. Higgins R, Kirklin JK, Brown RN, et al. To induce or not to induce: do patients at greatest risk for fatal rejection benefit from cytolytic induction therapy? J Heart Lung Transplant 2005;24(4):392-400
30. Baran DA. Induction therapy in cardiac transplantation: when and why? Heart Fail Clin 2007;3(1):31-41
31. Hong JC, Kahan BD. Immunosuppressive agents in organ transplantation: past, present, and future. Semin Nephrol 2000;20(2):108-125 (Pubitemid 30158481)
32. Halloran PF. Immunosuppressive drugs for kidney transplantation. N Engl J Med 2004;351(26):2715-29 •• Excellent discussion of T-cell activation and co-stimulatory pathways.
33. Rhen T, Cidlowski JA. Antiinflammatory action of glucocorticoids: new mechanisms for old drugs. N Engl J Med 2005;353(16):1711-1723 (Pubitemid 41464710)
34. Felkel TO, Smith AL, Reichenspurner HC, et al. Survival and incidence of acute rejection in heart transplant recipients undergoing successful withdrawal from steroid therapy. J Heart Lung Transplant 2002;21(5):530-539 (Pubitemid 34451024)
35. Mehra MR, Uber PA, Park MH, et al. Corticosteroid weaning in the tacrolimus and mycophenolate era in heart transplantation: clinical and neurohormonal benefits. Transplant Proc 2004;36(10):3152-3155 (Pubitemid 41126762)
36. Keogh A, Macdonald P, Harvison A, et al. Initial steroid-free versus steroidbased maintenance therapy and steroid withdrawal after heart transplantation: two views of the steroid question. J Heart Lung Transplant 1992;11(2 Pt 2):421-427
37. Rosenbaum DH, Adams BC, Mitchell JD, et al. Effects of early steroid withdrawal after heart transplantation. Ann Thorac Surg 2006;82(2):637-644 (Pubitemid 44088648)
38. O'Connell JB, Bristow MR, Rasmussen LG, et al. Cardiac allograft function with corticosteroid-free maintenance immunosuppression. Circulation 1990;82(5 Suppl):IV318-21 (Pubitemid 20381380)
39. Olivari MT, Jessen ME, Baldwin BJ, et al. Triple-drug immunosuppression with steroid discontinuation by six months after heart transplantation. J Heart Lung Transplant 1995;14(1 Pt 1):127-135
40. Hunt SA, Haddad F. The changing face of heart transplantation. J Am Coll Cardiol 2008;52(8):587-98 •• Comprehensive review of recent developments in heart transplantation.
41. Takeuchi H, Matsuno N, Hirano T, et al. Evidence of different pharmacokinetics between cyclosporine and tacrolimus in renal transplant recipients: why cyclosporine is monitored by C2 level and tacrolimus by trough level. Transplant Proc 2008;40(7):2240-2242
42. Kobashigawa JA, Miller LW, Russell SD, et al. Tacrolimus with mycophenolate mofetil (MMF) or sirolimus vs. cyclosporine with MMF in cardiac transplant patients: 1-year report. Am J Transplant 2006;6(6):1377-1386 (Pubitemid 44030320)
43. Grimm M, Rinaldi M, Yonan NA, et al. Superior prevention of acute rejection by tacrolimus vs. cyclosporine in heart transplant recipients: a large European trial. Am J Transplant 2006;6(6):1387-1397 (Pubitemid 44030321)
44. Elion GB. The purine path to chemotherapy. Science 1989;244(4900):41-47 (Pubitemid 19130741)
45. Eisen HJ, Kobashigawa J, Keogh A, et al. Three-year results of a randomized, double-blind, controlled trial of mycophenolate mofetil versus azathioprine in cardiac transplant recipients. J Heart Lung Transplant 2005;24(5):517-525 (Pubitemid 40693872)
46. Sehgal SN. Rapamune (RAPA, rapamycin, sirolimus): mechanism of action immunosuppressive effect results from blockade of signal transduction and inhibition of cell cycle progression. Clin Biochem 1998;31(5):335-340 (Pubitemid 28385231)
47. Panwalkar A, Verstovsek S, Giles FJ. Mammalian target of rapamycin inhibition as therapy for hematologic malignancies. Cancer 2004;100(4):657-666 (Pubitemid 38176841)
48. Keogh A, Richardson M, Ruygrok P, et al. Sirolimus in de novo heart transplant recipients reduces acute rejection and prevents coronary artery disease at 2 years: a randomized clinical trial. Circulation 2004;110(17):2694-700 • Clinical trial assessing efficacy of sirolimus therapy for prevention of acute rejection and coronary allograft vasculopathy. (Pubitemid 39453021)
49. Sindhi R, Webber S, Venkataramanan R, et al. Sirolimus for rescue and primary immunosuppression in transplanted children receiving tacrolimus. Transplantation 2001;72(5):851-855 (Pubitemid 32879857)
50. Gustafsson F, Ross HJ. Proliferation signal inhibitors in cardiac transplantation. Curr Opin Cardiol 2007;22(2):111-116 (Pubitemid 46220265)
51. Eisen HJ, Tuzcu EM, Dorent R, et al. Everolimus for the prevention of allograft rejection and vasculopathy in cardiactransplant recipients. N Engl J Med 2003;349(9):847-58 • Clinical trial assessing efficacy of everolimus for prevention of acute rejection and coronary allograft vasculopathy.
52. Kobashigawa J, Miller L, Renlund D, et al. A randomized active-controlled trial of mycophenolate mofetil in heart transplant recipients. Mycophenolate Mofetil Investigators. Transplantation 1998;66(4):507-15 • Clinical trial investigating efficacy of mycophenolate mofetil (MMF) for prevention of heart transplant rejection.
53. Manito N, Kaplinsky EJ, Bernat R, et al. Fatal interstitial pneumonitis associated with sirolimus therapy in a heart transplant recipient. J Heart Lung Transplant 2004;23(6):780-782 (Pubitemid 38721452)
54. Lindenfeld JA, Simon SF, Zamora MR, et al. BOOP is common in cardiac transplant recipients switched from a calcineurin inhibitor to sirolimus. Am J Transplant 2005;5(6):1392-1396 (Pubitemid 40839430)
55. Hamour IM, Mittal TK, Bell AD, Banner NR. Reversible sirolimus-associated pneumonitis after heart transplantation. J Heart Lung Transplant 2006;25(2):241-244 (Pubitemid 43156379)
56. Exposito V, de Prada JA, Gomez-Roman JJ, et al. Everolimus-related pulmonary toxicity in heart transplant recipients. J Heart Lung Transplant 2008;27(7):797-800
57. Kuppahally S, Al-Khaldi A, Weisshaar D, et al. Wound healing complications with de novo sirolimus versus mycophenolate mofetil-based regimen in cardiac transplant recipients. Am J Transplant 2006;6(5 Pt 1):986-992 (Pubitemid 44356648)
58. Kushwaha SS, Khalpey Z, Frantz RP, et al. Sirolimus in cardiac transplantation: use as a primary immunosuppressant in calcineurin inhibitor-induced nephrotoxicity. J Heart Lung Transplant 2005;24(12):2129-2136 (Pubitemid 41814736)
59. Hiatt WR, Nissen SE. Certican (everolimus) for the proposed indication of prophylaxis of rejection in heart transplantation; report from the Cardiovascular and Renal Drugs Advisory Committee, US food and drug administration, November 16, 2005, Rockville, MD. Circulation 2006;113:e394-e5
60. Lehmkuhl H, Hetzer R. Clinical experience with Certican (everolimus) in de novo heart transplant patients at the Deutsches Herzzentrum Berlin. J Heart Lung Transplant 2005;24(4 Suppl):S201-5; discussion S10-1 (Pubitemid 40379799)
61. Lyster H, Panicker G, Leaver N, Banner NR. Initial experience with sirolimus and mycophenolate mofetil for renal rescue from cyclosporine nephrotoxicity after heart transplantation. Transplant Proc 2004;36(10):3167- 3170 (Pubitemid 41126766)
62. Valantine H. Is there a role for proliferation signal/mTOR inhibitors in the prevention and treatment of de novo malignancies after heart transplantation? Lessons learned from renal transplantation and oncology. J Heart Lung Transplant 2007;26(6):557-564 (Pubitemid 46818047)
63. Kirklin JK, Brown RN, Huang ST, et al. Rejection with hemodynamic compromise: objective evidence for efficacy of photopheresis. J Heart Lung Transplant 2006;25(3):283-288 (Pubitemid 43290657)
64. Frist WH, Biggs VJ. Chronic myelogenous leukemia after lymphoid irradiation and heart transplantation. Ann Thorac Surg 1994;57(1):214-216 (Pubitemid 24047722)
65. Ross HJ, Gullestad L, Pak J, et al. Methotrexate or total lymphoid radiation for treatment of persistent or recurrent allograft cellular rejection: a comparative study. J Heart Lung Transplant 1997;16(2):179-189 (Pubitemid 27097854)
66. Reed EF, Demetris AJ, Hammond E, et al. Acute antibody-mediated rejection of cardiac transplants. J Heart Lung Transplant 2006;25(2):153-159 (Pubitemid 43156365)
67. Michaels PJ, Espejo ML, Kobashigawa J, et al. Humoral rejection in cardiac transplantation: risk factors, hemodynamic consequences and relationship to transplant coronary artery disease. J Heart Lung Transplant 2003;22(1):58-69 (Pubitemid 36071418)
68. Stewart S, Winters GL, Fishbein MC, et al. Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of heart rejection. J Heart Lung Transplant 2005;24(11):1710-1720
69. Pescovitz MD. Rituximab, an anti-cd20 monoclonal antibody: history and mechanism of action. Am J Transplant 2006;6(5 Pt 1):859-866 (Pubitemid 44356635)
70. Ramzy D, Rao V, Brahm J, et al. Cardiac allograft vasculopathy: a review. Can J Surg 2005;48(4):319-327 (Pubitemid 41297336)
71. Costanzo MR, Naftel DC, Pritzker MR, et al. Heart transplant coronary artery disease detected by coronary angiography: a multiinstitutional study of preoperative donor and recipient risk factors. Cardiac Transplant Research Database. J Heart Lung Transplant 1998;17(8):744-753 (Pubitemid 28396983)
72. Julius BK, Attenhofer Jost CH, Sutsch G, et al. Incidence, progression and functional significance of cardiac allograft vasculopathy after heart transplantation. Transplantation 2000;69(5):847-853 (Pubitemid 30174109)
73. Wenke K, Meiser B, Thiery J, et al. Simvastatin initiated early after heart transplantation: 8-year prospective experience. Circulation 2003;107(1):93-97 (Pubitemid 36070939)
74. Kobashigawa JA, Katznelson S, Laks H, et al. Effect of pravastatin on outcomes after cardiac transplantation. N Engl J Med 1995;333(10):621-627
75. Keogh A, Macdonald P, Kaan A, et al. Efficacy and safety of pravastatin vs simvastatin after cardiac transplantation. J Heart Lung Transplant 2000;19(6):529-537 (Pubitemid 30387058)
76. Cutts JL, Scallen TJ, Watson J, Bankhurst AD. Role of mevalonic acid in the regulation of natural killer cell cytotoxicity. J Cell Physiol 1989;139(3):550-557 (Pubitemid 19167827)
77. Weis M, Pehlivanli S, Meiser BM, et al. Simvastatin treatment is associated with improvement in coronary endothelial function and decreased cytokine activation in patients after heart transplantation. J Am Coll Cardiol 2001;38(3):814-818 (Pubitemid 32835758)
78. Akhlaghi F, Ashley J, Keogh A, Brown K. Cyclosporine plasma unbound fraction in heart and lung transplantation recipients. Ther Drug Monit 1999;21(1):8-16 (Pubitemid 29077449)
79. Weitz-Schmidt G, Welzenbach K, Brinkmann V, et al. Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site. Nat Med 2001;7(6):687-692 (Pubitemid 32588024)
80. Kwak B, Mulhaupt F, Myit S, Mach F. Statins as a newly recognized type of immunomodulator. Nat Med 2000;6(12):1399-1402 (Pubitemid 32001026)
81. Kobashigawa JA. Statins in solid organ transplantation: is there an immunosuppressive effect? Am J Transplant 2004;4(7):1013-1018
82. Schroeder JS, Gao SZ, Alderman EL, et al. A preliminary study of diltiazem in the prevention of coronary artery disease in heart-transplant recipients. N Engl J Med 1993;328(3):164-170 (Pubitemid 23021502)
83. Steinhauff S, Pehlivanli S, Bakovic-Alt R, et al. Beneficial effects of quinaprilat on coronary vasomotor function, endothelial oxidative stress, and endothelin activation after human heart transplantation. Transplantation 2004;77(12):1859-1865 (Pubitemid 38822209)
84. Bae JH, Rihal CS, Edwards BS, et al. Association of angiotensin- converting enzyme inhibitors and serum lipids with plaque regression in cardiac allograft vasculopathy. Transplantation 2006;82(8):1108-1111 (Pubitemid 44632129)
85. Erinc K, Yamani MH, Starling RC, et al. The effect of combined Angiotensinconverting enzyme inhibition and calcium antagonism on allograft coronary vasculopathy validated by intravascular ultrasound. J Heart Lung Transplant 2005;24(8):1033-1038 (Pubitemid 41127185)
86. Mehra MR, Ventura HO, Smart FW, et al. An intravascular ultrasound study of the influence of angiotensin-converting enzyme inhibitors and calcium entry blockers on the development of cardiac allograft vasculopathy. Am J Cardiol 1995;75(12):853-854
87. Pethig K, Hornig B, Bara C, et al. Eprosartan in the primary prevention of cardiac allograft vascular disease: a double-blind prospectively randomized study using intravascular ultrasound. J Int Med Res 2008;36(5):1022-1031
88. Lim DS, Mooradian SJ, Goldberg CS, et al. Effect of oral L-arginine on oxidant stress, endothelial dysfunction, and systemic arterial pressure in young cardiac transplant recipients. Am J Cardiol 2004;94(6):828-831 (Pubitemid 39221515)
89. Fang JC, Kinlay S, Beltrame J, et al. Effect of vitamins C and E on progression of transplant-associated arteriosclerosis: a randomised trial. Lancet 2002;359(9312):1108-1113 (Pubitemid 34270735)
90. Iwanaga K, Hasegawa T, Hultquist DE, et al. Riboflavin-mediated reduction of oxidant injury, rejection, and vasculopathy after cardiac allotransplantation. Transplantation 2007;83(6):747-753 (Pubitemid 46569193)
91. Meiser BM, Groetzner J, Kaczmarek I, et al. Tacrolimus or cyclosporine: which is the better partner for mycophenolate mofetil in heart transplant recipients? Transplantation 2004;78(4):591-598
92. Mancini D, Pinney S, Burkhoff D, et al. Use of rapamycin slows progression of cardiac transplantation vasculopathy. Circulation 2003;108(1):48-53 (Pubitemid 36859019)
93. Raichlin E, Bae JH, Khalpey Z, et al. Conversion to sirolimus as primary immunosuppression attenuates the progression of allograft vasculopathy after cardiac transplantation. Circulation 2007;116(23):2726-2733 (Pubitemid 350291245)
94. Schmauss D, Weis M. Cardiac allograft vasculopathy: recent developments. Circulation 2008;117(16):2131-41 • Comprehensive review of pathogenesis, histology, and treatment strategies for coronary allograft vasculopathy.
95. Salgar SK, Yang D, Ruiz P, et al. Viral interleukin-10-engineered autologous hematopoietic stem cell therapy: a novel gene therapy approach to prevent graft rejection. Hum Gene Ther 2004;15(2):131-144 (Pubitemid 38210529)
96. Minami E, Laflamme MA, Saffitz JE, Murry CE. Extracardiac progenitor cells repopulate most major cell types in the transplanted human heart. Circulation 2005;112(19):2951-2958 (Pubitemid 41612297)
97. Ochando JC, Homma C, Yang Y, et al. Alloantigen-presenting plasmacytoid dendritic cells mediate tolerance to vascularized grafts. Nat Immunol 2006;7(6):652-662 (Pubitemid 43797347)
98. Isobe M, Kosuge H, Suzuki J. T cell co-stimulation in the development of cardiac allograft vasculopathy: potential targets for therapeutic interventions. Arterioscler Thromb Vasc Biol 2006;26(7):1447-1456 (Pubitemid 44288968)
99. Newell KA, Larsen CP, Kirk AD. Transplant tolerance: converging on a moving target. Transplantation 2006;81(1):1-6 (Pubitemid 43122139)
100. Jordan SC, Vo A, Tyan D, Toyota M. Desensitization therapy with intravenous gammaglobulin (IVIG): applications in solid organ transplantation. Trans Am Clin Climatol Assoc 2006;117:199-211
101. Jordan S, Cunningham-Rundles C, McEwan R. Utility of intravenous immune globulin in kidney transplantation: efficacy, safety, and cost implications. Am J Transplant 2003;3(6):653-664 (Pubitemid 36745237)
102. Olsen SL, Wagoner LE, Hammond EH, et al. Vascular rejection in heart transplantation: clinical correlation, treatment options, and future considerations. J Heart Lung Transplant 1993;12(2):S135-42 (Pubitemid 23123852)
103. Hammond EH, Yowell RL, Nunoda S, et al. Vascular (humoral) rejection in heart transplantation: pathologic observations and clinical implications. J Heart Transplant 1989;8(6):430-443 (Pubitemid 20044096)
104. Kazatchkine MD, Kaveri SV. Immunomodulation of autoimmune and inflammatory diseases with intravenous immune globulin. N Engl J Med 2001;345(10):747-755 (Pubitemid 34936657)
105. Jordan SC, Tyan D, Stablein D, et al. Evaluation of intravenous immunoglobulin as an agent to lower allosensitization and improve transplantation in highly sensitized adult patients with end-stage renal disease: report of the NIH IG02 trial. J Am Soc Nephrol 2004;15(12):3256-3262 (Pubitemid 39578859)
106. Jordan SC, Quartel AW, Czer LS, et al. Posttransplant therapy using high-dose human immunoglobulin (intravenous gammaglobulin) to control acute humoral rejection in renal and cardiac allograft recipients and potential mechanism of action. Transplantation 1998;66(6):800-805 (Pubitemid 28460117)
107. De Marco T, Damon LE, Colombe B, et al. Successful immunomodulation with intravenous gamma globulin and cyclophosphamide in an alloimmunized heart transplant recipient. J Heart Lung Transplant 1997;16(3):360-365 (Pubitemid 27138301)
108. Pradhan M, Raffaelli RM, Lind C, et al. Successful deceased donor renal transplant in a sensitized pediatric recipient with the use of plasmapheresis. Pediatr Transplant 2008;12(6):711-716
109. Vo AA, Lukovsky M, Toyoda M, et al. Rituximab and intravenous immune globulin for desensitization during renal transplantation. N Engl J Med 2008;359(3):242-251 (Pubitemid 352008439)
110. Keown PA. Use of cyclosporine microemulsion (Neoral) in de novo and stable renal transplantation: clinical impact, pharmacokinetic consequences and economic benefits. Canadian and International Neoral Study Groups. Transplant Proc 1996;28(4):2147-2150 (Pubitemid 26282404)
111. White M, Pelletier GB, Tan A, et al. Pharmacokinetic, hemodynamic, and metabolic effects of cyclosporine sandimmune versus the microemulsion neoral in heart transplant recipients. J Heart Lung Transplant 1997;16(8):787-794 (Pubitemid 27362678)
112. Yabu JM, Vincenti F. Novel immunosuppression: small molecules and biologics. Semin Nephrol 2007;27(4):479-486 (Pubitemid 47002072)
113. Vincenti F. Chronic induction. What's new in the pipeline. Contrib Nephrol 2005;146:22-29
114. Reichert JM. Monoclonal antibodies in the clinic. Nat Biotechnol 2001;19(9):819-822 (Pubitemid 32816751)
115. Bretscher P, Cohn M. A theory of self-nonself discrimination. Science 1970;169(950):1042-1049
116. Linsley PS, Ledbetter JA. The role of the CD28 receptor during T cell responses to antigen. Annu Rev Immunol 1993;11:191-212 (Pubitemid 23115006)
117. Butler JA, Roderick P, Mullee M, et al. Frequency and impact of nonadherence to immunosuppressants after renal transplantation: a systematic review. Transplantation 2004;77(5):769-776 (Pubitemid 38366989)
118. First MR, Fitzsimmons WE. Modified release tacrolimus. Yonsei Med J 2004;45(6):1127-1131 (Pubitemid 40136672)
119. Florman S, Alloway R, Kalayoglu M, et al. Conversion of stable liver transplant recipients from a twice-daily Prograf-based regimen to a once-daily modified release tacrolimus-based regimen. Transplant Proc 2005;37(2):1211-1213 (Pubitemid 40590839)
120. Tedesco Silva H Jr, Pinheiro Machado P, Rosso Felipe C, et al. Immunotherapy for de novo renal transplantation: what's in the pipeline? Drugs 2006;66(13):1665-1684
121. Behrend M. Adverse gastrointestinal effects of mycophenolate mofetil: aetiology, incidence and management. Drug Saf 2001;24(9):645-663 (Pubitemid 32761719)
122. Salvadori M, Holzer H, de Mattos A, et al. Enteric-coated mycophenolate sodium is therapeutically equivalent to mycophenolate mofetil in de novo renal transplant patients. Am J Transplant 2004;4(2):231-236 (Pubitemid 38248526)
123. Budde K, Curtis J, Knoll G, et al. Enteric-coated mycophenolate sodium can be safely administered in maintenance renal transplant patients: results of a 1-year study. Am J Transplant 2004;4(2):237-243 (Pubitemid 38248527)
124. Kobashigawa JA, Renlund DG, Gerosa G, et al. Similar efficacy and safety of enteric-coated mycophenolate sodium (EC-MPS, myfortic) compared with mycophenolate mofetil (MMF) in de novo heart transplant recipients: results of a 12-month, single-blind, randomized, parallel-group, multicenter study. J Heart Lung Transplant 2006;25(8):935-941 (Pubitemid 44143008)
125. Kunzendorf U, Ziegler E, Kabelitz D. FTY720-the first compound of a new promising class of immunosuppressive drugs. Nephrol Dial Transplant 2004;19(7):1677-1681 (Pubitemid 38961373)
126. Pan S, Mi Y, Pally C, et al. A monoselective sphingosine-1-phosphate receptor-1 agonist prevents allograft rejection in a stringent rat heart transplantation model. Chem Biol 2006;13(11):1227-1234 (Pubitemid 44762192)
127. Salvadori M, Budde K, Charpentier B, et al. FTY720 versus MMF with cyclosporine in de novo renal transplantation: a 1-year, randomized controlled trial in Europe and Australasia. Am J Transplant 2006;6(12):2912-2921 (Pubitemid 44777921)
128. Tedesco-Silva H, Pescovitz MD, Cibrik D, et al. Randomized controlled trial of FTY720 versus MMF in de novo renal transplantation. Transplantation 2006;82(12):1689-1697 (Pubitemid 46035653)
129. Huwiler A, Pfeilschifter J. New players on the center stage: sphingosine 1-phosphate and its receptors as drug targets. Biochem Pharmacol 2008;75(10):1893-1900
130. Shimizu H, Takahashi M, Kaneko T, et al. KRP-203, a novel synthetic immunosuppressant, prolongs graft survival and attenuates chronic rejection in rat skin and heart allografts. Circulation 2005;111(2):222-229 (Pubitemid 40139735)
131. Bilolo KK, Ouyang J, Wang X, et al. Synergistic effects of malononitrilamides (FK778, FK779) with tacrolimus (FK506) in prevention of acute heart and kidney allograft rejection and reversal of ongoing heart allograft rejection in the rat. Transplantation 2003;75(11):1881-1887 (Pubitemid 36734646)
132. Birsan T, Dambrin C, Klupp J, et al. Effects of the malononitrilamide FK778 on immune functions in vitro in whole blood from non-human primates and healthy human volunteers. Transpl Immunol 2003;11(2):163-167 (Pubitemid 36740808)
133. Savikko J, Von Willebrand E, Hayry P. Leflunomide analogue FK778 is vasculoprotective independent of its immunosuppressive effect: potential applications for restenosis and chronic rejection. Transplantation 2003;76(3):455-8; discussion 71-73 (Pubitemid 37013246)
134. Waldman WJ, Knight DA, Blinder L, et al. Inhibition of cytomegalovirus in vitro and in vivo by the experimental immunosuppressive agent leflunomide. Intervirology 1999;42(5-6):412-418 (Pubitemid 30122078)
135. Faguer S, Hirsch HH, Kamar N, et al. Leflunomide treatment for polyomavirus BK-associated nephropathy after kidney transplantation. Transpl Int 2007;20(11):962-969 (Pubitemid 47537566)
136. Zeng H, Waldman WJ, Yin DP, et al. Mechanistic study of malononitrileamide FK778 in cardiac transplantation and CMV infection in rats. Transplantation 2005;79(1):17-22 (Pubitemid 40139995)
137. Qi S, Zhu S, Xu D, et al. Significant prolongation of renal allograft survival by delayed combination therapy of FK778 with tacrolimus in nonhuman primates. Transplantation 2003;75(8):1124-1128 (Pubitemid 36513007)
138. Vanrenterghem Y, van Hooff JP, Klinger M, et al. The effects of FK778 in combination with tacrolimus and steroids: a phase II multicenter study in renal transplant patients. Transplantation 2004;78(1):9-14 (Pubitemid 38938277)
139. Borie DC, O'Shea JJ, Changelian PS. JAK3 inhibition, a viable new modality of immunosuppression for solid organ transplants. Trends Mol Med 2004;10(11):532-541 (Pubitemid 39433822)
140. Podder H, Kahan BD. Janus kinase 3: a novel target for selective transplant immunosuppression. Expert Opin Ther Targets 2004;8(6):613-629 (Pubitemid 40028370)
141. Saemann MD, Zeyda M, Stulnig TM, et al. Janus kinase-3(JAK3) inhibition: a novel immunosuppressive option for allogeneic transplantation. Transpl Int 2004;17(9):481-489 (Pubitemid 39592734)
142. Papageorgiou AC, Wikman LE. Is JAK3 a new drug target for immunomodulationbased therapies? Trends Pharmacol Sci 2004;25(11):558-562
143. Kudlacz E, Perry B, Sawyer P, et al. The novel JAK-3 inhibitor CP-690550 is a potent immunosuppressive agent in various murine models. Am J Transplant 2004;4(1):51-57 (Pubitemid 38155489)
144. Rousvoal G, Si MS, Lau M, et al. Janus kinase 3 inhibition with CP-690,550 prevents allograft vasculopathy. Transpl Int 2006;19(12):1014-1021 (Pubitemid 44684122)
145. Busque S, Leventhal JR, Brennan D. CP-690,550, a JAK3 inhibitor, in de novo kidney transplant recipients: 6-month results of a phase 2 trial. Am J Transplant 2007;7(Suppl 2):304
146. Tan SL, Parker PJ. Emerging and diverse roles of protein kinase C in immune cell signalling. Biochem J 2003;376(Pt 3):545-552 (Pubitemid 38058054)
147. Slade AV, Hijazi Y, Wagner J. NVP-AEB071: pharmacokinetics and pharmacodynamic activity of a novel T-cell activation inhibitor under multiple-dose conditions [abstract]. Am J Transplant 2006;6:198
148. Hariharan S, Johnson CP, Bresnahan BA, et al. Improved graft survival after renal transplantation in the United States, 1988 to 1996. N Engl J Med 2000;342(9):605-612
149. Aspeslet L, Freitag D, Trepanier D, et al. ISA (TX)247: a novel calcineurin inhibitor. Transplant Proc 2001;33(1-2):1048-1051
150. Larsen CP, Pearson TC, Adams AB, et al. Rational development of LEA29Y (belatacept), a high-affinity variant of CTLA4-Ig with potent immunosuppressive properties. Am J Transplant 2005;5(3):443-453 (Pubitemid 40313335)
151. Vincenti F, Larsen C, Durrbach A, et al. Costimulation blockade with belatacept in renal transplantation. N Engl J Med 2005;353(8):770-781 (Pubitemid 41215486)
152. Nicolls MR, Gill RG. LFA-1(CD11a) as a therapeutic target. Am J Transplant 2006;6(1):27-36
153. Nakakura EK, Shorthouse RA, Zheng B, et al. Long-term survival of solid organ allografts by brief anti-lymphocyte function-associated antigen-1 monoclonal antibody monotherapy. Transplantation 1996;62(5):547-552 (Pubitemid 26313892)
154. Scheinfeld N. Alefacept: a safety profile. Expert Opin Drug Saf 2005;4(6):975-985 (Pubitemid 41671596)
155. Vincenti F, Kirk AD. What's next in the pipeline? Am J Transplant 2008;8(10):1972-1981
156. Hideshima T, Mitsiades C, Akiyama M, et al. Molecular mechanisms mediating antimyeloma activity of proteasome inhibitor PS-341. Blood 2003;101(4):1530-1534 (Pubitemid 36182530)
157. Ekbal NJ, Holt DW, Macphee IA. Pharmacogenetics of immunosuppressive drugs: prospect of individual therapy for transplant patients. Pharmacogenomics 2008;9(5):585-596 . (Pubitemid 351803918)