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Published on: November 8, 2015
[Cyclosporin in heart transplantations. The authors' personal experience]
1Falk Cardiovascular Research Center, Stanford University School of Medicine.
Insights
Cyclosporine A (CsA) revolutionized organ transplantation, significantly improving graft survival and enabling more heart transplants. While effective, CsA has drawbacks including nephrotoxicity and increased risk of B-cell lymphoma.
Area of Science:
- Immunology
- Transplant Surgery
- Pharmacology
Background:
- Organ transplantation faced significant challenges with graft rejection prior to the advent of effective immunosuppressants.
- Cyclosporine A (CsA) emerged as a groundbreaking immunosuppressive agent, transforming the landscape of organ transplantation.
- The development of CsA marked a pivotal moment, enabling previously difficult or abandoned transplant procedures.
Purpose of the Study:
- To evaluate the impact of Cyclosporine A (CsA) on organ transplant outcomes, particularly in renal, liver, and heart transplantation.
- To assess the efficacy of CsA in preventing graft rejection and improving patient survival rates.
- To identify the primary benefits and drawbacks associated with CsA therapy in transplant recipients.
Main Methods:
- Review of historical data and clinical outcomes in organ transplantation before and after the introduction of CsA.
- Analysis of graft survival rates, patient survival, and rejection episodes in various transplant types.
- Examination of the pharmacological action of CsA on T-lymphocytes and its clinical side effects.
Main Results:
- CsA significantly improved graft survival in renal transplantation, reducing the importance of HLA matching.
- CsA enabled the widespread success of liver and heart transplantation, which were previously limited by rejection.
- Cardiac transplant survival at Stanford improved from 40% (1-year) and 20% (5-year) pre-CsA to 83% (1-year) and 50% (6-7 years) post-CsA.
Conclusions:
- Cyclosporine A is a critical immunosuppressant that has dramatically improved organ transplant success rates and expanded the feasibility of complex procedures.
- While CsA offers substantial benefits, its use is associated with significant drawbacks, including nephrotoxicity and an increased risk of post-transplant lymphoproliferative disease.
- CsA remains a gold standard for immunosuppression, guiding the development of newer therapeutic agents in transplantation.
Abstract:
The discovery of cyclosporine A (CsA) was a major development in the evolution of organ transplantation. In renal transplantation use of CsA improved graft survival such that HLA-matching is no longer as important and determinant as before. Liver transplantation prior to the arrival of CsA was almost abandoned by Starzl because of uncontrollable rejection. Hearth transplantation, after initial enthusiasm, was soon restricted to few centers as the difficulties in caring for these patients became apparent. Availability of CsA allowed more than 2500 hearth transplants to be performed annually today. At Stanford initially cardiac transplant survival at one year was 40% and at 5 years was approx 20%. The best results in patients treated with azathioprine-prednisone, just prior to the introduction of cyclosporine, were 65% and 40%. At present survival is 83% at 1 year and 50% at 6-7 years, as in other active centers around the world. CsA is the first drug specifically developed to target immunocompetent T-lymphocytes, and is the gold standard model for other new drugs. Its action is modification of rejection, so that when it occurs it is less acute in onset and less fulminant. The prevalence and mortality of infections have also been reduced. The major drawback of cyclosporine is nephrotoxicity: all patients undergo a progressive decline in creatinine clearance and within one year 90% have hypertension. A second problem is post-transplant lymphoproliferative disease, that takes the form of an aggressive and potentially lethal B-cell lymphoma appearing most commonly within one year from surgery.(ABSTRACT TRUNCATED AT 250 WORDS)
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