Major advances in surgery and in immunosuppressive drugs have made organ and tissue transplantation a more routine procedure. Nevertheless, the procedures still have risks, including an increased risk of developing cancer, particularly skin cancers and lymphomas. But one approachactually lowering the dosage and number of immunosuppressive drugsmay spare patients some of the ill effects of long-term immunosuppression.
Thomas Starzl, M.D., Ph.D., of the Thomas E. Starzl Transplantation Center at the University of Pittsburgh, and colleagues published a study in May in the Lancet that outlined a novel approach to immunosuppressive therapy: Patients were pretreated with the immunosuppressant antithymocyte globulin, and their post-transplant therapy was kept to a minimum. The study involved 82 patients receiving kidney, liver, pancreas, or intestinal transplantation.
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He said the secret is in the pre-transplant immunosuppression. After the transplant, doctors limit the immunosuppression regimen to the drug tacrolimus and only use other drugs as needed. About 4 months after transplantation, the patients are evaluated for less frequent dosingfor example, every other day, three times per week, or once per week.
In this way, graft tolerance is built up, he said, "and if you dont give a lot of immunosuppression, youre not going to get a lot of cancers." He said that eventually his team hopes to be able to stop immunosuppression entirely at about one year in liver transplant recipients.
A group at St. Vincents Hospital in Sydney, Australia, is also conducting studies of lower doses of immunosuppressive drugs, in this case in lung transplant patients. At the American Thoracic Societys annual meeting in Seattle in May, Monique A. Malouf, M.D., and colleagues reported that they combined lower doses of cyclosporin with high doses of valacyclovir to prevent post-transplant lymphoproliferative disease. They noted that 220 patients so treated had remained well for 312 to 821 days. They also noted that in cases where the patient was Epstein-Barr negative, the antiviral was given prophylactically.
Several studies have found that there is a doseresponse relationship between immunosuppressive drugs and risk of developing cancer. Added to that is the fact that survival after organ transplantation is increasing, and more transplant patients are developing cancer as they get older. Both Starzls and Maloufs approaches are aimed at reducing the complications from immunosuppression and ultimately reducing cancer risk as much as possible.
"We look at cancers three different ways," said H. Myron Kauffman M.D., consultant to the United Network of Organ Sharing (UNOS), who is a retired transplant surgeon from the Medical College of Wisconsin, Milwaukee. "First, the ones that are transmitted through the donor organ; second, we look at patients whove had a transplant and have a history of cancer sometime in their past; and then the third thing we look at is de novo cancers, which we know [are] much higher in the transplant patient than in the population at large." He added that cancers that develop from a tumor in the donor organ are a rare event.
Kauffman noted that potential organ donors who have any past history of melanoma or choriocarcinoma are excluded from the donation pool because of the increased incidence of those cancers in transplant recipients. UNOS is also concerned about donors who have had cancers of the lung, colon, breast, kidney, and thyroid, and about donors who have had lymphomas, to which transplant recipients are particularly susceptible.
UNOS reported that between 1994 and 2001 there were only 18 donor-related cancers found in patients who received 34,933 cadaver donations, and three donor-related cancers in the 32,052 patients who received transplants from living donors.
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