Induction and maintenance of immunosuppressive therapy in cardiac transplantation

INTRODUCTION

The goal of immunosuppression is to prevent or treat cardiac allograft rejection while minimizing drug toxicities as well as the major sequelae of immune suppression, namely infection and malignancy. Most clinically used immunosuppressive regimens consist of a combination of several agents used concurrently and follow several general principles.

Immunosuppressive regimens can be classified as induction, maintenance, or anti-rejection. Induction regimens provide intense early post-operative immune suppression while maintenance regimens are used throughout the patient's life to prevent both acute and chronic rejection. This topic will review the induction and maintenance immunosuppressive regimens used in heart transplantation. The management of acute allograft rejection and the diagnosis and allograft vasculopathy are discussed separately. (See "Acute cardiac allograft rejection: Treatment" and "Prevention and treatment of cardiac allograft vasculopathy".)

GENERAL PRINCIPLES

Three general principles govern induction and maintenance immunosuppressive therapy regimens. The first principle is that immune reactivity and tendency toward graft rejection are highest early (within the first three to six months) after graft implantation and decrease with time. Thus, most regimens employ the highest intensity of immunosuppression immediately after surgery and decrease the intensity of therapy over the first year, eventually settling on the lowest maintenance levels of immunosuppression that are compatible with preventing graft rejection while minimizing drug toxicities. The second principle is to use low doses of several drugs with non-overlapping toxicities in preference over higher (and more toxic) doses of fewer drugs whenever feasible. The third principle is to avoid over-immunosuppression, because it leads to a myriad of undesirable effects including susceptibility to infection and malignancy. (See "Infection in the solid organ transplant recipient" and "Development of malignancy following solid organ transplantation" and "Treatment and prevention of post-transplant lymphoproliferative disorders".)

INDUCTION THERAPY

The overall strategy of using induction therapy and the optimal regimen to achieve a state of early intense immunosuppression remain controversial. Approximately 50 percent of heart transplant programs currently employ a strategy of augmented immunosuppression, or induction therapy, during the early postoperative period [1]. Several anti-lymphocyte antibodies that target specific epitopes on the surface of both B and T cells have been used as part of induction therapy.

The goal of induction therapy is to provide intense immunosuppression when the risk of allograft rejection is highest. From a clinical perspective, the main advantages of induction therapy are to allow delayed initiation of nephrotoxic immunosuppressive drugs in patients with compromised renal function prior to or following surgery and to provide some flexibility with respect to early glucocorticoid weaning or use of glucocorticoid-sparing baseline regimens after transplantation [2-4].

                                        

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Literature review current through: Mar 2014. | This topic last updated: Mar 5, 2014.
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