Trends in Immunosuppressive Therapy With Regard to Cytolytic Induction Therapy and Corticosteroid Withdrawal

  • J. Kobashigawa


A cytolytic agent (e.g. antilymphocyte serum) administered immediately after heart transplantation (HTx) is known as ‘induction’ therapy and is given in the hope of inducing graft tolerance[1]–[4]. The benefit of this form of therapy remains controversial, as no randomized studies have been performed. Forms of antilymphocyte sera include murine monoclonal antibody (OKT3), rabbit and equine antithymocyte globulin (ATG), and antilymphocyte globulin (ALG).


Heart Transplantation Rejection Episode Heart Lung Transplant Steroid Withdrawal Corticosteroid Withdrawal 
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  1. 1.
    Kaye MP, Bristow MR, Rose E, Starnes V. Monoclonal antibody therapy: new approaches to immunosuppression in cardiac transplantation. Monograph produced by Pro/Com, 1988.Google Scholar
  2. 2.
    Starnes VA, Oyer PE, Stinson EB, Dein JR, Shumway NE. Prophylactic OKT3 used as induction therapy for heart transplantation. Circulation. 1989;80(Suppl. III):III–79.Google Scholar
  3. 3.
    Kirklin JK, Bourge RC, White-William C et al. Prophylactic therapy for rejection after cardiac transplantation. J Thorac Cardiovasc Surg. 1990;99:716.PubMedGoogle Scholar
  4. 4.
    Carey JA, Frist WH. Use of polyclonal antilymphocytic preparations for prophylaxis in heart transplantation. J Heart Transplant. 1990;9:297.PubMedGoogle Scholar
  5. 5.
    Weimar W, Essed CE, Balk ML et al. OKT3 delays rejection crisis after heart transplantation. Transplant Proc. 1989;21:2497.PubMedGoogle Scholar
  6. 6.
    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(Suppl. IV):IV–291.Google Scholar
  7. 7.
    Olivari MT, Kubo SH, Braunlin EA. Bolman RM III, Ring WS. Five-year experience with triple-drug immunosuppressive therapy in cardiac transplantation. Circulation. 1990;82(Suppl. IV):IV–276.Google Scholar
  8. 8.
    Prieto M, Lake KD, Pritzker MR et al. OKT3 induction and steroid-free maintenance immunosuppression for treatment of high-risk heart transplant recipients. J Heart Lung Transplant. 1991;10:901.PubMedGoogle Scholar
  9. 9.
    Kobashigawa JA, Kirklin JK, Naftel DC and the Transplant Cardiologists Research Database Group. Pre-transplant risk factors for acute rejection after cardiac transplantation: A multi-institutional study. J Heart Lung Transplant. 1993;12:355.PubMedGoogle Scholar
  10. 10.
    Renlund DG, O’Connell JB, Gilbert EM et al. A prospective comparison of murine monoclonal CD-3 (OKT3) antibody and equine antithymocyte globulin-based rejection prophylaxis in cardiac transplantation. Transplantation. 1989;47:599.PubMedCrossRefGoogle Scholar
  11. 11.
    Wollnek G, Laufer G, Laczkovis A, Buxbaum P, Kober I. Comparison of monoclonal anti-T cell antibody vs ATG as prophylaxis after heart transplantation. Transplant Proc. 1989;21:2499.Google Scholar
  12. 12.
    Griffith BP, Kormos RL, Armitage JM, Dummer JS, Hardesty RL. Comparative trial of immunoprophylaxis with RATG versus OKT3. J Heart Transplant. 1990;9:301.PubMedGoogle Scholar
  13. 13.
    Costanzo-Nordin MR, O’Sullivan JE, Johnson MR el al. Prospective randomized trial of OKT3 versus horse antithymocyte globulin-based immunosuppressive prophylaxis in heart transplantation. J Heart Transplant. 1990;9:306.PubMedGoogle Scholar
  14. 14.
    Ladowski JS, Dillon T, Schatzlein MH et al. Prophylaxis of heart transplant rejection with either antithymocyte globulin, Minnesota antilymphocyte globulin, or an OKT3-based protocol. J Cardiovasc Surg. 1993;34:135.Google Scholar
  15. 15.
    Copeland JG, Icenogle TB, Williams RJ et al. Rabbit antithymocyte globulin. A 10-year experience in cardiac transplantation. J Thorac Cardiovasc Surg. 1990;99:852.PubMedGoogle Scholar
  16. 16.
    Miller LW, Naftel DC, Bourge RC et al. Infection after heart transplantation: a multiinstitutional study. J Heart Lung Transplant. 1994; 13:381.PubMedGoogle Scholar
  17. 17.
    Kirklin JK, Naftel DC, Levine TB and the Cardiac Transplant Research Database Group. Cytomegalovirus after heart transplantation. Risk factors for infection and death: a multiinstitutional study. J Heart Lung Transplant. 1994;513:P394.Google Scholar
  18. 18.
    Costanzo-Nordin MR, Swinnen LJ, Fisher SG et al. Cytomegalovirus infections in heart transplant recipients; relationship to immunosuppression. J Heart Lung Transplant. 1992;11:837.PubMedGoogle Scholar
  19. 19.
    Swinnen LJ, Costanzo-Nordin MR, Fisher SG et al. Increased incidence of lymphoproliferative disorder after immunosuppression with the monoclonal antibody OKT3. N Engl J Med. 1990;323:1723.PubMedCrossRefGoogle Scholar
  20. 20.
    Hammond EH, Whittner CT, Greenwood J et al. Relationship of OKT3 sensitization and vascular rejection in cardiac transplant patients receiving OKT3 rejection prophylaxis. Transplant. 1990;50:776.CrossRefGoogle Scholar
  21. 21.
    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:S135.PubMedGoogle Scholar
  22. 22.
    Hammond EH, Yowell RL, Numoda S et al. Vascular (humoral) rejection in heart transplantation in pathologic observations and clinical implications. J Heart Transplant. 1989;8:430.PubMedGoogle Scholar
  23. 23.
    Normann SJ, Saloman DR, Leclachaikul P et al. Acute vascular rejection of the coronary arteries in human heart transplantation: pathology and correlations with immuno-suppression and cytomegalovirus infection. J Heart Lung Transplant. 1991;10:674.PubMedGoogle Scholar
  24. 24.
    Lake K, Anderson D, Milfred S et al. The incidence of cytomegalovirus disease is not increased after OKT3 induction therapy. J Heart Lung Transplant. 1993;12:537.PubMedGoogle Scholar
  25. 25.
    Kormos RL, Trento A, Hardesty RL et al. Avoidance of perioperative renal toxicity by a modified immunosuppression protocol. Transplant Proc. 1987;19:2525.PubMedGoogle Scholar
  26. 26.
    Menkis AH, Powell AM, Novick RJ et al. Prospective randomized trial of short term immunosuppressive prophylaxis using OKT3 or Minnesota equine ALG. J Heart Lung Transplant. 1992;11:569.PubMedGoogle Scholar
  27. 27.
    Alonso-Pulpon L, Serrano-Fiz S, Rubio JA et al. Efficacy of low-dose OKT3 as cytolytic induction therapy in heart transplantation. J Heart Lung Transplant. 1995;14:136.PubMedGoogle Scholar
  28. 28.
    Kobashigawa JA, Stevenson LW, Brownfield EB et al. Does short-course induction with OKT3 improve outcome after heart transplantation? A randomized trial. J Heart Lung Transplant. 1993;12:250.Google Scholar
  29. 29.
    Yacoub M, Alivizatos P, Khaghani A, Mitchell A. The use of cyclosporin, azathioprine, and antithymocyte globulin with or without low-dose steroids for immunosuppression of cardiac transplant patients. Transplant Proc. 1985;17:221.Google Scholar
  30. 30.
    Renlund DG, O’Connell JB, Gilbert EM et al. Feasibility of discontinuation of corticosteroid maintenance therapy in heart transplantation. J Heart Transplant. 1987;6:71.PubMedGoogle Scholar
  31. 31.
    Price GD, Olsen SL, Taylor DO et al. Corticosteroid-free maintenance immunosuppression after heart transplantation; feasibility and beneficial effect. J Heart Lung Transplant. 1992;11:403.PubMedGoogle Scholar
  32. 32.
    Kobashigawa JA, Stevenson LW, Brownfield ED et al. Initial success of steroid weaning late after heart transplantation. J Heart Lung Transplant. 1992; 11:428.PubMedGoogle Scholar
  33. 33.
    Miller LW, Wolford T, McBride LR, Peigh P, Pennington DG. Successful withdrawal of corticosteroids in heart transplant. J Heart Lung Transplant. 1992; 11:431.PubMedGoogle Scholar
  34. 34.
    Keogh A, Macdonald P, Harbison A et al. Initial steroid-free vs steroid-based maintenance therapy and steroid withdrawal after heart transplantation: two views of the steroid question. J Heart Lung Transplant. 1992;11:421.PubMedGoogle Scholar
  35. 35.
    Pritzker MR, Lake K, Reutzel T et al. Minneapolis Heart Institute Experience. J Heart Lung Transplant. 1992;11:415.PubMedGoogle Scholar
  36. 36.
    Esmore DS, Spratt PM, Keogh AM et al. Cyclosporinc and azathioprine immuno-suppression without maintenance steroids: a prospective randomized trial. J Heart Transplant. 1989;8:194.PubMedGoogle Scholar
  37. 37.
    Kobashigawa JA, Stevenson LW, Brownfield ED et al. Corticosteroid weaning late after heart transplantation: relation to HLA-DR mismatching and long-term metabolic benefits. J Heart Lung Transplant. 1995;14:963.PubMedGoogle Scholar
  38. 38.
    Wechsler ME, Giardina EG, Sciacca RR, Rose EA, Barr ML. Increased early mortality in women undergoing cardiac transplantation. Circulation. 1995;91:1029.PubMedGoogle Scholar
  39. 39.
    Miller LW, Schlant RC, Kobashigawa JA, Kubo S, Renlund DG. 24th Bethesda Conference: Cardiac Transplantation (Task Force 5: Complications). J Am Coll Cardiol. 1993;22:41.PubMedCrossRefGoogle Scholar
  40. 40.
    Renlund DG, Bristow MR, Crandall BG et al. Hypercholesterolemia after heart transplantation; amelioration by corticosteroid-free maintenance immunosuppression. J Heart Transplant. 1989;8:214.PubMedGoogle Scholar
  41. 41.
    Hagan ME, Holland CS, Herrick CM and the Utah Cardiac Transplant Program. Amelioration of weight gain after heart transplantation by corticosteroid-free maintenance immunosuppression. J Heart Transplant. 1990;9:382.PubMedGoogle Scholar
  42. 42.
    Merrell SW, Ames SA, Nelson EW et al. Major abdominal complications following cardiac transplantation. Arch Surg. 1989;124:889.PubMedGoogle Scholar
  43. 43.
    Baum MF, Cutler DC, Fricker FJ et al. Physiologic and psychological growth and development in pediatric heart transplant recipients. J Heart Lung Transplant. 1991;10:848.PubMedGoogle Scholar
  44. 44.
    Au J, Gregory JW, Colquehoun IW et al. Paediatric cardiac transplantation with steroid-sparing maintenance immunosuppression. Arch Dis Child. 1992;67:1262.PubMedCrossRefGoogle Scholar
  45. 45.
    Ratkovec RM, Wray RB, Renlund DG et al. Influence of corticosteroid-free maintenance immunosuppression on allograft coronary artery disease after cardiac transplantation. J Thorac Cardiovasc Surg. 1990;100:6.PubMedGoogle Scholar
  46. 46.
    O’Connell JB, Bristow MR, Rasmussen LG et al. Cardiac allograft function with corticosteroid-free maintenance immunosuppression. Circulation. 1990;82:IV–318.Google Scholar
  47. 47.
    Jones B, Taylor F, Wright O, et al. Quality of life after heart transplantation in patients assigned to double or triple drug therapy. J Heart Transplanl. 1990;9:392.Google Scholar

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© Kluwer Academic Publishers 1996

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  • J. Kobashigawa

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