摘要:

The clinical success of solid-organ transplantation took a great leap forward in the early 1980s with the development of cyclosporin A. In synergy with corticosteroids and the antimetabolite azathioprine, cyclosporin A significantly reduced cell-mediated graft rejection and allowed for successful organ transplantation. Despite the great clinical success produced by this triple-drug regimen, however, enthusiasm was tempered for two reasons: 1) the particular toxicities of the agents and 2) the nonspecific immunosuppression produced by the regimen, which resulted in opportunistic infections and increased malignancies. Thus, efforts in developing new immunosuppressive treatments for transplantation have focused on developing specific immunomodulation and on agents that might additionally produce attenuation of the antibody response, which is believed to be important in the development of chronic rejection.

ISSN:1087-2418    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Immunosuppression, although necessary to enable the graft to escape the consequences of immune surveillance, carries some risks for the patient. There is an associated increase in neoplasms, opportunistic infections, and end-organ toxicity. In addition, even with excellent patient compliance, rejection (acute and chronic) remains a major limitation that contributes to the loss or decrease in the function of the allograft. New drugs have been added to the armamentarium of immunosuppressive agents to suppress allograft rejection and to rescue grafts from cyclosporine-resistant rejection. Most of the immunosuppressive agents in use today are directed at the T lymphocyte, nonspecifically inhibiting T-cell activation and proliferation. One of these new immunosuppressive agents is tacrolimus.

ISSN:1087-2418    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Since the introduction of cyclosporine in 1983, graft and patient survival rates in organ transplant surgery have improved dramatically. However, rejection episodes are still frequent and are a major cause of acute and chronic graft loss. High-dose pulse steroids remain the preferred primary agent for the treatment of all initial rejection episodes for most vascularized solid organ allografts. For steroid refractory rejection episodes, a growing number of potent immunosuppressive drugs are now available. Antilymphocyte globulins and monoclonal mouse antihuman CD3 antibody therapy, OKT3, remain useful for the treatment of steroid-resistant rejections. However, newly available agents such as tacrolimus or mycophenolate mofetil, developed for maintenance immunosuppressive therapy to prevent rejection, represent an attractive and potentially effective alternative to antilymphocyte antirejection therapy. Moreover, tacrolimus and mycophenolate mofetil appear to have the potential to replace antilymphocyte therapy as the agent of choice for the treatment of steroid-resistant rejections in recipients of cyclosporine-based immunosuppression, whereas OKT3 or antilymphocyte globulin may be reserved for refractory rejection rather than as firstline agents. Clearly, an important advantage of tacrolimus and mycophenolate mofetil is related to their ability to salvage grafts in cases where the rejection is resistant to the treatment of antilymphocyte globulin or OKT3 therapy-before the availability of tacrolimus and mycophenolate mofetil, such grafts were often lost. Other exciting drugs are available experimentally for the treatment of rejection, and in the not too distant future should enter the clinical arena to further affect the rapidly changing field of transplantation.

ISSN:1087-2418    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

There has been significant improvement in 1-year renal allograft survival over the last decade. The major goal in managing long-term immunosuppression is to balance the benefits of long-term therapy against the known and unknown long-term risk. Risk factors associated with long-term renal graft failure have been defined. An analysis of the United Network for Organ Sharing database between 1988 and 1994 showed that recipient race, transplant center effect, and donor age account for a substantial proportion of the risk of long-term graft failure. Over the past 3 years, the choices available for long-term immunosuppression have increased with the availability of mycophenolate mofetil (MMF), tacrolimus (FK506), and the microemulsion formula of cyclosporin A. This article examines the major immunosuppressive therapies used for long-term prevention of renal allograft rejection.

ISSN:1087-2418    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The goal of transplantation is to achieve host immunologic tolerance to foreign tissue, thereby allowing the withdrawal of immunosuppressive therapy without ensuing rejection. Among multiple strategies employed to achieve this goal is the utilization of monoclonal antibodies that target an array of T-cell surface antigenic molecules. Current therapeutic approaches utilizing murine monoclonal antibodies are accompanied by pan-T cell suppression, increased incidence of infectious complications, and the development of host antimurine antibody responses that limit the antibody therapeutic potential and preclude retreatment. Recombinant DNA technology has provided multiple novel agents that induce selective immunosuppression and serve to dissect the immune response to better define the nature of complex molecular interactions leading to alloactivation. Such agents will undoubtedly be adopted in future clinical protocols.

ISSN:1087-2418    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

This review examines current trends and practices in immunosuppression for pediatric solid organ transplantation, with emphasis on renal transplantation. Current immunosuppression has permitted improved patient and graft survival rates. Current practice includes, in various combinations, the use of immunophyllin binding agents such as cyclosporine or tacrolimus, a corticosteroid, and an anti-proliferative agent such as azathioprine or mycophenolate mofetil. The benefits and challenges of each of these agents in pediatrics is reviewed. With improved immunosuppression, the attention of the pediatric transplant community has turned to ameliorating long-term adverse effects such as growth retardation, corticosteroid side-effects, and malignancies.

ISSN:1087-2418    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Immunotoxins are highly selective biological agents that target tumor cells or cells of the immune system with lethal precision. Because of toxic side effects, clinical use of immunotoxins has been limited to date. New developments, however, in monoclonal antibody technology as well as in the molecular design of toxins have created new constructs that hold promise for clinical application in organ transplantation and bone marrow transplantation. Principles of immunotoxin design and function are reviewed, and preliminary results of a new anti-T-cell immunotoxin are presented. Preclinical studies show promise for using immunotoxins to induce specific immunologic tolerance to organ transplants.

ISSN:1087-2418    

出版商:OVID    

年代:1997

数据来源: OVID