Monday, January 28, 2008

[StemCells] Organ Donor's Marrow to prevent immune rejection trials

Northwestern Memorial trial may wean kidney transplant patients off
antirejection drugs
New study transplants stem cells from a kidney donor's bone marrow
into the recipient, with the hope of gradually eliminating the need
for antirejection drugs
CHICAGO — 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."

###
About Northwestern Memorial Hospital

Northwestern Memorial Hospital is one of the country's premier
academic medical centers and is the primary teaching hospital of the
Northwestern University Feinberg School of Medicine. Northwestern
Memorial and its Prentice Women's Hospital and Stone Institute of
Psychiatry have 897 beds along with 1,424 affiliated physicians and
6,464 employees. Northwestern Memorial is recognized for providing
state-of-the-art patient care and exemplary clinical and surgical
advancements in the areas of cardiothoracic and vascular care,
gastroenterology, neurology and neurosurgery, oncology, organ and
bone marrow transplantation, and women's health.

Northwestern Memorial received the prestigious 2005 National Quality
Health Care Award and is listed in eight specialties in U.S. News &
World Report's 2007 rankings for "America's Best Hospitals." For
seven years running, Northwestern Memorial has been rated among the
nation's "100 Best Companies for Working Mothers" by Working Mother
magazine and has been chosen by Chicagoans for more than a decade as
their "most preferred hospital" according to the National Research
Corporation's annual survey. Northwestern Memorial carries the Magnet
status designation in nursing, the highest recognition possible for
patient care and nursing excellence.

Public release date: 22-Jan-2008
Contact: Amy Dobrozsi
adobrozs@nmh.org
312-926-5900
Northwestern Memorial Hospital

http://www.eurekalert.org/pub_releases/2008-01/nmh-nmt012208.php

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StemCells subscribers may also be interested in these sites:

Children's Neurobiological Solutions
http://www.CNSfoundation.org/

Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123

The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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