Feb. 5, 2002 PITTSBURGH, Feb. 4 – A grateful sister got more than her brother's kidney; she also got millions of cells from his immune system in a procedure that transplant surgeons at the University of Pittsburgh's Thomas E. Starzl Transplantation Institute, working with the University of Pittsburgh Cancer Institute, hope will allow her eventual freedom from all anti-rejection drugs.
The technique, called peripheral blood stem cell transplantation, is standard for patients with certain types of cancers, but in what is believed to be a first, it was tried in a non-cancer patient receiving a kidney from a living donor as a means to induce drug-free tolerance of the transplanted organ.
On Jan. 11, a 54-year-old woman received a kidney donated by her 47-year-old brother. Three days later, in a simple bedside procedure taking less than 20 minutes, the woman also received an infusion of her brother's immune system cells taken from blood he had donated during a four-hour outpatient session this past month. Both donor and recipient were discharged five days after transplant.
"So far, we are pleased with how the donor and recipient are doing. By all indications, the recipient's transplanted kidney is functioning well, and she has had no complications from the stem cell infusion. But it is too soon to know if the stem cell infusion will be effective. It will be several months or more before we'll determine whether it is safe to begin weaning her off immunosuppressive drugs," said the recipient's surgeon, Velma Scantlebury, M.D., associate professor of surgery at the Thomas E. Starzl Transplantation Institute.
"Unlike liver transplant patients, very few kidney recipients have been able to be safely weaned off immunosuppression. We think this is because the kidney contains less of the types of cells that are immunoprotective. It is presumed that the blood stem cell transplant will introduce enough of these good immune system cells to protect the organ from rejection," explained Ron Shapiro, M.D., professor of surgery with the Starzl Transplant Institute and the donor’s surgeon.
Of the more than 13,000 kidney transplants that took place in the United States last year, more than 5,000 were transplants from living donors. Even patients who receive transplants from living donors must take a life-long regimen of immunosuppressant drugs to protect their organs from being rejected. Such drugs can cause serious complications, such as tumor growth, and make patients more susceptible to infections.
Transplant tolerance, which refers to the state by which a patient's immune system has fully accepted a transplanted organ, is a key area of study at the University of Pittsburgh. For nearly a decade, surgeons have been evaluating the long-term benefits of giving organ transplant recipients unmodified donor bone marrow infusions as a means to enhance chimerism, the coexistence of donor and recipient cells. About 300 patients have received donor bone marrow with their transplants, including nine living donor kidney transplant recipients.
As with the earlier transplants with bone marrow, the aim of the new treatment is to boost the level of chimerism, with the idea that tolerance is more likely to follow and successful weaning can occur. (None of the bone marrow patients have been completely weaned, but most are on reduced doses of anti-rejection drugs.) The transplant team believes the new treatment has advantages for both the donor and the recipient. The donor procedure is performed in an outpatient setting as opposed to in the operating room, and a greater quantity of specific cells can be obtained for infusion into the recipient.
"The content of lymphocytes in peripheral blood progenitor cells is 100 times more than in bone marrow, so we expect to be able to induce an enhanced state of chimerism, and eventually achieve tolerance of the transplanted organ," explained Andrew Yeager, M.D., professor of medicine and pediatrics, University of Pittsburgh School of Medicine, and director of the Stem Cell Transplant Center at the University of Pittsburgh Cancer Institute.
"With tolerance, we'd be able to taper the drugs or even wean the patient off the drugs completely. This would be a significant feat because most kidney transplant patients eventually develop chronic rejection, necessitating for some a return to dialysis or retransplantation," added Dr. Shapiro.
Peripheral blood stem cell transplantation is an accepted practice for the treatment of different cancers, including lymphomas and leukemia. As with cancer patients, the kidney donor was treated first with a growth factor (G-CSF, or granulocyte colony-stimulating factor) to stimulate blood cell growth. Then, four days later, using a procedure called leukapheresis, blood was withdrawn from one of his veins, the stem cells filtered out, and his blood returned. (The process, which takes about three or four hours, can be repeated if a sufficient volume of cells is not obtained in one session.) The stem cells were then placed in a special medium and frozen until their infusion into the kidney transplant recipient.
Stem cell transplantation has never been used in conjunction with living donor kidney transplantation. At the University of Miami, surgeons have tried the procedure in a handful of patients undergoing living donor liver transplants.
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