Allograft Survival with Calcineurin Inhibitors

The immunosuppressive drugs cyclosporine A (CsA) and tacrolimus (FK506), also called calcineurin inhibitors, have truly revolutionized allograft transplantation. The introduction of CsA in 1976 was the first major advance in transplantation since the introduction of prednisone and azathioprine made allograft transplantation possible in the early 1950s and 1960s. FK506 was approved in 1994 and led to dramatic improvements in solid organ transplantation, allowing highly antigenic lymph node bearing allografts, such as the small bowel, to be transplanted. Recently, FK506 monotherapy has successfully allowed combined small bowel and partial abdominal wall transplantation in humans. The success of FK506 and CsA has made them key drugs in the modern era of transplantation. The purine synthesis inhibitor mycophenolate mofetil (MMF) was approved in 1995, and the drug Sirolimus (rapamycin) was introduced in 1999. Combining these drugs with calcineurin inhibitors has significantly reduced the incidence of acute rejection and improved solid organ allograft survival, with a reduction in adverse effects.