Jan. 24, 2008 After a transplant surgery, anti-rejection drugs for the organ recipient are a must, but with prolonged use can have serious side effects, including infections, heart disease and cancer. A team led by Joshua Miller, MD, a researcher at Northwestern University's Feinberg School of Medicine, is working with Northwestern Memorial Hospital's department of organ transplantation to enroll qualifying subjects in a new research study that seeks to transplant stem cells from a kidney donor's bone marrow into the recipient, with the hope of gradually eliminating the need for anti-rejection drugs. If research proves successful, it would mean a dramatic change in the post-transplant quality of life for the transplant recipient.
Northwestern is the only center in Chicago and one of four centers nationally looking at this topic. The Feinberg School of Medicine has received a four-year, $2.5 million grant from the National Institutes of Health to enroll 20 patients in the study, which is called "Donor Stem Cells, Campath, T/B Cell Regulation In HLA-Identical Renal Transplants."
The first subjects to participate in the study underwent kidney transplant surgery on Thursday, Jan. 10. Sharon Flood of Pingree Grove, Ill. donated her kidney to her brother Steven Yelk of Gurnee, Ill., who suffers from polycystic kidney disease (PKD), which causes cysts filled with fluid to form throughout the kidneys. Eventually, these cysts take over the healthy kidney tissue and the kidneys fail. "Our family is very close and there are seven brothers and sisters, I was thrilled to learn that I was a match and would be able to help Steven," Sharon commented before the surgery.
Joseph Leventhal, MD, PhD, transplant surgeon, associate professor of surgery and director of the Living Donor Renal Transplant Program at Northwestern University's Feinberg School of Medicine, preformed the kidney donor's surgery and Michael Abecassis, MD, MBA, chief of the division of transplantation, and dean of clinical affairs for Northwestern University's Feinberg School of Medicine, performed the recipient's surgery.
"The surgery was successful, everything went according to plan and the new kidney is functioning well," said Dr. Abecassis. From here, the kidney recipient will begin the experimental portion of the study.
This study is open to HLA-identical sibling kidney donor and recipient pairs. HLA, or human leukocyte antigen, is one of a group of proteins found on the surface of white blood cells and other cells that play an important part in the body's immune response to foreign substances. These antigens vary from person to person, and an HLA compatibility test is performed before organ transplantation to find out if tissues match between a donor and a recipient.
The study is limited to only HLA-identical sibling pairs because these siblings genetically have a more similar set of immunologic markers than a non-related HLA-identical pair. Because this population has the closest genetic relationship, they have the best chance for success with the study. Overall, HLA-identical siblings have very low rejection rates for kidney transplants but until now have still required immunosuppressive drugs to be taken for life.
How does it work?
Stem cells are formed at the marrow and are common blood cells from which other specialized blood cells, like immune cells, develop. These stem cells are considered important to help prevent rejection of the kidney transplant. By transplanting these cells from the kidney donor into the recipient, the study seeks to prove that the stem cells will mature in the recipient's body and will allow his immune system to accept the new organ as his own.
For the kidney donor, the laparoscopic surgery occurs in the standard manner. After the kidney is removed, bone marrow is drawn from the donor's hip bone. About three months following the surgery, the donor undergoes two procedures called leukopheresis, happening one day apart, where stem cells mobilized from the marrow are collected so that they can be given to the kidney recipient to help his body acclimate to the transplant.
Approximately one month before the transplant surgery, the recipient undergoes leukopheresis to draw white blood cells which are stored in a lab for later testing. After transplant surgery, the recipient receives four separate infusions of donor stem cells.
The stem cells are infused into the transplant recipient via an IV in a procedure that lasts about 15 minutes. The first infusion is five days after surgery, the next is about three months after surgery, then six months and finally nine months after the transplant. During this time the recipient is treated with Campath-1H, a potent antibody used extensively at Northwestern to prevent rejection, in addition to the other standard anti-rejection medications. About a year after the surgery, the subject is weaned off of one anti-rejection drug, then another. There are also ongoing tests to ensure the recipient is tolerating the kidney.
"This is an exciting area of research which holds a great deal of promise if successful," says Dr. Abecassis. "We are excited to be the only center in the region offering this to qualifying patients."
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