Transplant researchers at the University of Pittsburgh's Thomas E. Starzl Transplantation Institute have dramatically improved intestinal transplant graft survival, and reduced rejection and infection rates by successfully using a novel immunosuppression minimization protocol, thus improving patients' overall quality of life and avoiding the use of several anti-rejection drugs, which can cause serious infections and major complications.
Because the intestine is especially prone to rejection and infection, results of this innovative clinical protocol presented today at the 3rd International Conference on Immunosuppression at the Manchester Grand Hyatt, San Diego, are significant and have the potential to advance the field of organ transplantation.
"Transplant recipients do not want to be overwhelmed with a lot of anti-rejection medications, which can often lead to more complications. The fact that we have been able to significantly reduce the amount of anti-rejection drugs in this group of patients has enabled many of them to live full and productive lives," said Kareem Abu-Elmagd, M.D., Ph.D., F.A.C.S., professor of surgery at the University of Pittsburgh School of Medicine and director of the Intestinal Rehabilitation and Transplant Center at the University of Pittsburgh Medical Center's (UPMC) Thomas E. Starzl Transplantation Institute and lead author of the study.
Of the 123 small bowel patients (65 intestine, 25 liver/intestine and 33 multivisceral) who received transplants under the immunosuppression minimization protocol since July 2001, 109 recipients are alive with 107 having functioning grafts. One-year survival rate is 96 percent. Sixty-nine percent of patients are taking a single dose of immunosuppression, some once a day, while others twice a week.
The protocol involves giving a one-time pre-transplant dose of either the drug thymoglobulin – a drug that kills and depletes T cells – key immune system cells that target the donor organ, or a similar drug called campath, which depletes both T and B cells, immune system cells involved in organ rejection.
Following transplantation, the 103 patients who received thymoglobulin and the 20 patients who received campath received the standard anti-rejection drug tacrolimus and none of the patients received steroids. Tapering of tacrolimus was attempted after 120 days.
While 43 percent of patients experienced some level of rejection before initial weaning, none showed evidence of chronic rejection. Patients under the campath protocol did slightly better than those treated with thymoglobulin.
Of the 123 intestinal transplants, 55 involved children, while the other 68 were adult cases.
The current success of this novel anti-rejection protocol should allow major improvement in both the long-term efficacy and quality of life after intestinal and multivisceral transplants, according to the researchers.
"This study, which is the first of its kind in the small bowel patient population at the University of Pittsburgh, was intentionally done because the intestine is an organ most capable of producing an immune response. With the success of reducing the anti-rejection drugs in these patients, we recommend this treatment regimen for other patients undergoing abdominal organ transplants (i.e., liver, kidney, pancreas) or thoracic organ transplants (i.e., heart or lung). At UPMC, the protocol has already been applied to the other organ transplant recipients, after the encouraging results with the initial intestinal transplant recipients," added Dr. Abu-Elmagd.
UPMC has more clinical experience with intestinal transplants than any other transplant center in the world. Since May 1990, more than 400 patients have undergone various intestinal transplants at UPMC. Survival rates also continue to improve each year; approximately 90 percent of patients survive after the first year. The overall five-year patient survival rate is 70 percent and 10-year patient survival rate is 42 percent. An adult and child transplanted more than 14 years ago at the University of Pittsburgh are the world's longest surviving recipients of a liver-intestine transplant.
In April 2001, the Centers for Medicare and Medicaid Services approved transplants of the small bowel, based on an appeal made by the transplant surgeons at the University of Pittsburgh.