Transplant turnabout

Weaning patients off drugs

The last 12 years of kidney transplant patient Lupe Alcaraz’s life were awful. She was often sick, her immune system crippled from decades of taking immunosuppressive drugs. She needed steroids too, which weakened her bones.

“It was just really ugly,” recalls her daughter, Cynthia Alcaraz-Jew.

When Alcaraz died in 2010, Alcaraz-Jew’s own kidneys were failing — her family suffers from a genetic condition called Alport syndrome, which causes kidney, eye and ear problems. Months later, as Alcaraz-Jew, now 47, slogged through yet another year of dialysis, she got some wonderful news: Her younger brother, Xavier, could donate his perfectly matched kidney, and she qualified for a Stanford study that attempts to wean transplant patients off the immunosuppressive drugs.

“I couldn’t have been happier,” she says.

Now, less than two years after her transplant, Alcaraz-Jew is drug free, living proof that an experimental treatment developed by Stanford immunologist Samuel Strober, MD, and his colleagues has the potential to improve the health of hundreds, perhaps thousands, of transplant patients. Stanford is one of just a few research institutes working to wean these patients off immunosuppressants.

Strober studied the immune system for decades before formulating the treatment, which thwarts the battle between a patient’s immune system and a donated organ. The medications dampen the response, but they can also cause heart disease, infections and even kidney failure — a bitter irony for someone who just received a new kidney, says Strober, a professor of immunology and rheumatology. 

The treatment starts the day after the transplant. For 10 days, the team irradiates the primary immune organs, including the lymph nodes, thymus and spleen, then injects a serum that contains antibodies allowing it to recognize and kill a type of immune cell called a T cell.

Several weeks later, Strober’s team injects the patient with cells from the donor: a combination of mature and immature immune cells. Once injected, the immature cells, known as stem cells, must mature and mix with the patient’s cells to prevent an immune attack.

“They’ve got to stick and stay,” says John Scandling, MD, the kidney transplant specialist who works with Strober. “That’s the challenge.”

The treatment is most effective with well-matched donors, and the team has tried it only with kidneys because kidneys can be donated from a living patient, who can also supply stem cells.

Of the 24 kidney transplant patients with perfectly matched donors who enrolled in the trial beginning in 2000, 16, including Alcaraz-Jew, are living drug free, and three others are working to get off the medications, Strober says. The team is planning to publish a paper summarizing the research results in the near future.

To treat patients who don’t have a perfectly matched donor, the team has been experimenting with the amounts and types of donor cells needed.

“The idea is to make this applicable to everybody,” says Scandling, a professor of nephrology.

Now, however, Alcaraz-Jew is reveling in her hard-won health with her husband and two daughters. They recently returned from Cancún, where they swam with whale sharks, a feat that would have been unimaginable two years ago.

“It changed my life completely,” Alcaraz-Jew says. 

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