Stanford study finds transplant patient thrives 2 years after stopping immunosuppressive drugs

January 23, 2008

STANFORD, Calif. - Luck smiled on Larry Kowalski when his brother agreed to donate a kidney Kowalski needed to live. He was even luckier that his brother's kidney was such a good match.

That last stroke of luck led Kowalski to connect with a team of researchers at the Stanford University School Medicine, whose efforts have enabled him for two years to live free of the heavy-duty drugs that transplant patients normally have to take for the rest of their lives.

The researchers describe Kowalski's case in a brief report to be published in the Jan. 24 issue of The New England Journal of Medicine on the technique they developed, based on 25 years of research by Samuel Strober, MD, professor of immunology and rheumatology. The journal issue also includes two reports from other research groups, describing their efforts to achieve organ transplantation without long-term immunosuppressive drugs.

Kowalski, now 50, was 3 years old when doctors discovered he had been born with only one kidney. His single kidney held out until he was 47. Then a blood test indicated that it was beginning to fail.

Kowalski's 49-year-old brother agreed to help, and that turned out to be crucial. His brother was a perfect fit of the six proteins most important in matching the immune systems of transplant donors with recipients.

Transplant recipients are matched as closely as possible with the donor organs to minimize the body's normal response to reject the organs. The biggest danger with organ transplantation lies not in the surgery, but in the recipient's own body rejecting the organ as a foreign invader. Without drugs to suppress that reaction, usually the recipient's immune system encounters unfamiliar proteins on the transplanted organ, attacks the organ and eventually destroys its function.

But unless the recipient has an identical twin, there will always be some minor differences between the organs, so even close matches require a lifetime of immunosuppressive drugs. Long-term use of these drugs can cause cancer, bothersome side effects and, most ironic for kidney transplant recipients, kidney damage.

The ultimate goal for transplant patients is to get their bodies to tolerate their donor organs without drugs. Transplant doctors have been trying to develop ways to do this for years, with little success.

The fact that Kowalski had such a good match with his brother's kidney made him an ideal candidate for the Stanford clinical study. The researchers were investigating whether a procedure that involved adjusting Kowalski's immune system, plus infusing blood cells from the brother who donated the kidney, could allow Kowalski's body to tolerate his brother's kidney.

The therapy was first developed in mice by Strober, the senior author of the study. In the last few years, Strober worked with Robert Lowsky, MD, associate professor of blood and marrow transplantation, to adapt this strategy from mice for human lymphoma and leukemia patients. The procedure combines localized blasts of irradiation and antibody treatments to tweak the recipient's immune cells. Then the recipient gets an infusion of blood cells from the donor. The procedure boosts levels of a type of immune cell called regulatory T cells. These cells function as the immune system's "peacekeepers" and can avert the attack that causes rejection.

When the Stanford transplant team approached Kowalski with the offer, he jumped at the chance that might allow him to forego a lifetime of immunosuppressive drugs.

In February 2005, Kowalski received his brother's kidney at Stanford Hospital. He was started on an immunosuppressive drug with the intention that it would be temporary. His only notable complication came about a month after his transplant, when Kowalski had to be hospitalized briefly for a fever. He returned to work as a restaurant owner three months after the transplant.

Doctors began to taper the use of the immunosuppressive drug and, after six months, Kowalski was drug-free.

"Essentially, my immune system contains half my brother's immune cells and half of my own," said Kowalski. "It's enough that my body thinks my brother's kidney is mine."

After all the mouse studies leading up to testing in patients, Kowalski's case is rewarding for Strober. "It's been a long, long road that ends up with clinical trials that could lead to somebody's benefit," he said. "Tolerance has been the goal for decades, and we are just now beginning to see the fruits of all that labor."

Kowalski could be called the poster child of the procedure so far, but others in the same research study haven't fared as well. Six other patients treated before him haven't been able to go off of their drugs, but their kidneys came from donors not as perfectly matched as Kowalski's was.

He was the first patient in a new iteration of the technique that is being tried only in perfectly matched donors and recipients. So far, one patient that followed Kowalski is showing promising results but is not yet off the drugs, said lead author John Scandling, MD, professor of nephrology and Kowalski's kidney transplant specialist.

The research team found Kowalski "remains in good health" 34 months after he stopped taking the immunosuppressive drugs. An interview with Kowalski shows this to be an understatement. Not only does he run four restaurants in California, but he bikes, snowboards, scuba dives, goes to the gym regularly and, most taxing of all, is the father of a 3-year-old. By anyone's definition, he is in great health.

"The idea of getting off drugs holds tremendous appeal for patients," said Scandling. "So far, there is hope, but we still have a long way to go."
-end-
This study was supported by a grant from the National Heart, Lung, and Blood Institute.

Others from Stanford who contributed to this work are: Stephan Busque, MD, associate professor of surgery; Sussan Dejbakhsh-Jones, research associate in immunology and rheumatology; Claudia Benike, research associate in pathology; Maria Millan, MD, adjunct professor of surgery; Judith Shizuru, MD, PhD, associate professor of blood and marrow transplantation; Richard Hoppe, MD, professor and chair of radiation oncology, and Edgar Engleman, MD, professor of pathology and of medicine.

Stanford University Medical Center integrates research, medical education and patient care at its three institutions - Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital at Stanford. For more information, please visit the Web site of the medical center's Office of Communication & Public Affairs at http://mednews.stanford.edu.

Stanford University Medical Center

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.