New! Sign up for our free email newsletter.
Science News
from research organizations

Therapy Developed At Cedars-Sinai Medical Center Shows Promise In Preventing Rejection Of Transplanted Organs

Date:
May 11, 1999
Source:
Cedars-Sinai Medical Center
Summary:
A therapeutic approach that appears to significantly reduce the rejection risk of transplanted organs is currently being studied in multi-center clinical trials but already has been adopted as an effective tool by most major transplant centers throughout the country.
Share:
FULL STORY

A therapeutic approach that appears to significantly reduce the rejection risk of transplanted organs is currently being studied in multi-center clinical trials but already has been adopted as an effective tool by most major transplant centers throughout the country.

The therapy, infusion of intravenous immunoglobulin (IVIG), appears to be helpful in preventing rejection in difficult cases when other medications have failed, according to Stanley C. Jordan, M.D., director of Pediatric Nephrology and Transplant Immunology, and medical director of the Renal Transplant Program at Cedars-Sinai Medical Center.

Led by Dr. Jordan, researchers at Cedars-Sinai Medical Center began to develop the concept of using gammaglobulin in a transplant environment in the late 1980s as IVIG was becoming established as a therapy for immune system disorders. "IVIG treatment has given the gift of life to many patients who would not have had a chance at transplantation or would have died or languished on dialysis without the hope of a life-saving transplant," Dr. Jordan said.

Immunoglobulins are proteins naturally produced within the body that can act as antibodies -- natural defenses against invading organisms called antigens. A processed form of immunoglobulin made from blood plasma can be administered to bolster the body's natural levels. For transplant specialists looking to modify the immune system so that it will accept the "foreign tissue" of a transplanted organ, IVIG products possess several appealing properties.

"We have other very powerful drugs that are currently available to suppress the immune system but there is a price to pay. They make the patient more susceptible to infectious complications because most of the medications are globally immunosuppressive," said Dr. Jordan. "The good thing about IV gammaglobulin therapy is that it modulates the immune system, it doesn't suppress it, and it doesn't predispose the patient to infectious complications. We think that it is able to "turn off" deleterious immune responses without damaging the immune system. In fact, we believe it strengthens the immune system because it provides antibodies to infectious agents as well."

In short, patients at high risk of rejection have "bad" antibodies in their systems that would reject a transplanted kidney. IVIG contains "good" antibodies that block the ability of the bad ones to cause rejection.

Using therapeutic protocols developed for use in kidney transplantation -- one protocol for adults and the other for children -- Dr. Jordan is coordinating clinical trials that are sponsored by the National Institutes of Health. Begun in 1994, the studies are expected to provide statistical documentation to support the benefits that have been seen in clinical practice.

In the adult study, which will continue for the next several years, neither clinical staff nor patient knows who is receiving IVIG therapy and who is receiving a placebo. The pediatric trial, which is nearing completion, also started as a blinded study but was modified to "open-label" status to provide the medication for all children in the study.

Although the current studies are intended to prove or disprove the effectiveness of IVIG therapy in kidney transplant situations, the treatment also appears beneficial in heart, lung and liver transplants. According to a paper published in the Sept. 27, 1998 issue of "Transplantation," IVIG is recognized as an effective therapy in treating challenging forms of both heart and kidney rejection.

Dr. Jordan said IVIG therapy produces few side effects, and those are minor. The most common problem associated with the treatment is headache at the time of infusion.

While the uncertainty of donor organ availability makes it impossible to predict each patient's course of treatment, the objective of therapy is to introduce IVIG into the patient's system before transplantation and immediately thereafter in an effort to modulate a possible immune response. According to study protocols, treatments are given once a month for four months before transplantation. For patients who receive a transplanted kidney, four additional doses are administered. Those who do not receive a transplant are given another dose of IVIG at one year and again at two years after the initial infusions.

Elaine Elizabeth Small, who celebrated her 23rd birthday on May 1, successfully received a kidney donated by her mother, Scarlett S. Small, last December -- in spite of having numerous health problems dating back 14 years. Elaine was diagnosed at age 9 with a connective tissue disorder, which later was determined to be a form of lupus. Despite repeated attempts with a variety of medications to treat the disease and arrest its progress, Elaine required a full knee replacement and a partial knee replacement at age 16.

Eventually, the toxicity of the various medications began to damage Elaine's kidneys. In November 1995, Scarlett was told that Elaine's kidney function had been reduced to less than 10 percent of normal and she would need hemodialysis to stay alive. The next three years were spent battling infections, undergoing additional surgery for the removal of a section of small intestine, and contending with more complications.

"I can't put into words the emotional stress that the family went through, but particularly her because she had dealt with not being well all of her life," said Scarlett, who with her husband, Walter Small, Sr., has two other children, ages 27 and 19. "Instead of things getting better it seemed that as we conquered one small area something major came along."

Before finding Dr. Jordan and the team at Cedars-Sinai, the family had been told that because of Elaine's recurring antibiotic-resistant infections and the continuing assault of lupus on her system, she could not be considered for a transplant. But when Elaine's father learned of studies directed at improving the odds of patients who had complex health issues, they scheduled an appointment with Dr. Jordan.

In March 1998, Elaine went to Cedars-Sinai for her first IVIG treatment, although because this was part of the ongoing clinical study, neither the family nor the medical staff knew at the time if she was receiving IVIG or a placebo. In October, Scarlett underwent a series of medical tests and found that she could be a compatible kidney donor. Despite several more physical setbacks for Elaine, the mother-to-daughter transplant was finally completed on Dec. 2.

"We were both in the surgery prep room around 7 or 7:30 that morning," said Scarlett. "And I knew that it would be fine. We prayed together and she told me that she hoped that I would be OK. I told her that I would if she would be OK."

After the operations and the two patients had been taken to their rooms two floors apart, Scarlett called Elaine on the phone. Elaine was ecstatic that her new kidney had started to function immediately. "She just started crying and we both just cried," said Scarlett.

Elaine passed the three-month post-transplant mark with only two minor threats of rejection that required adjustments in medications, according to Scarlett. She is now thoroughly enjoying all the foods that patients on hemodialysis must avoid in order to maintain electrolyte balance, proper fluid levels and other vital functions.

Scarlett said Elaine, who suffers irreversible hearing loss as a result of the numerous infections she endured through the years, recently said, "Mom, I didn't think I would live to see my 21st birthday. Who would have thought that I'll be 23?"

Despite its apparent benefits, this therapy is likely to remain a viable anti-rejection option only in difficult cases and when other treatments fail, partly because immunoglobulin is a limited commodity. The product of a painstaking and time-consuming laboratory process, IVIG is in high demand for the treatment of a variety of immune system disorders. The medication's limited availability has actually slowed the completion of the clinical trials underway.

"Our work in development of IVIG therapy as an agent to prevent and treat transplant rejection has already changed pediatric transplant practices," said Dr. Jordan. "The data generated from our lab and clinical programs have already shown that this treatment has significant promise for many patients, both adult and pediatric."


Story Source:

Materials provided by Cedars-Sinai Medical Center. Note: Content may be edited for style and length.


Cite This Page:

Cedars-Sinai Medical Center. "Therapy Developed At Cedars-Sinai Medical Center Shows Promise In Preventing Rejection Of Transplanted Organs." ScienceDaily. ScienceDaily, 11 May 1999. <www.sciencedaily.com/releases/1999/05/990511074939.htm>.
Cedars-Sinai Medical Center. (1999, May 11). Therapy Developed At Cedars-Sinai Medical Center Shows Promise In Preventing Rejection Of Transplanted Organs. ScienceDaily. Retrieved March 28, 2024 from www.sciencedaily.com/releases/1999/05/990511074939.htm
Cedars-Sinai Medical Center. "Therapy Developed At Cedars-Sinai Medical Center Shows Promise In Preventing Rejection Of Transplanted Organs." ScienceDaily. www.sciencedaily.com/releases/1999/05/990511074939.htm (accessed March 28, 2024).

Explore More

from ScienceDaily

RELATED STORIES