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Study suggests breakthrough in organ transplants

A small pilot study indicates that following up an imperfectly matched organ transplant with an infusion of the donor's stem cells may free recipients from a lifetime of anti-rejection drugs.

March 08, 2012|By Melissa Healy | Los Angeles Times

Dr. Abraham Shaked, chief of the University of Pennsylvania's Department of Transplantation Surgery, who was not involved in the study, said uncertainties persist: It's not clear, for one thing, whether patients who are enabled to tolerate a mismatched kidney also have weakened "early warning" responses to infections and cancers.

Still, Shaked called the results "absolutely remarkable" and "beyond any expectations."

The team, led by transplant specialist Dr. Suzanne T. Ildstad, director of the Institute for Cellular Therapeutics at the University of Louisville in Kentucky, first prepared each patient with whole-body irradiation and several days of chemotherapy to suppress an immune response and make space in the blood for a new army of immune cells.

Two days after the kidney transplant operation, patients got an infusion of bioengineered immune cells from the kidney donor.

In almost every way, the second transplantation resembled a bone marrow transplant — a treatment that's been used to treat blood cancers such as leukemia and lymphoma for decades. But Ildstad's team defied a cardinal rule: to never transfer an incompatible HLA match from one person to another because it will rarely take.

They got away with it — no patients died and five developed tolerance for their kidney — through tweaking the mix of donor cells transplanted into the patient to induce "chimerism" — a state in which the immune system accepts dissimilar tissue as its own.

Key to this was refining each donor's stew of cells into an elixir enriched for adult stem cells, the early descendants of stem cells, and a heretofore unrecognized class of cells dubbed "tolerogenic graft-facilitating cells" by the study authors.

In a controversial move to protect their commercial interest in the newly described therapy, the authors declined to detail what those cells were and how they are identified and treated. But they reported that earlier studies in mice revealed that these facilitating cells "potently prevent graft-versus-host disease."

Transplant recipients were sent home with strict instructions to avoid exposure to sick people and germs and to wash their hands carefully for several days until their new, chimeric immune system stirred to life.

At one month after the transplants, three of the eight patients failed to achieve the state that would allow ongoing acceptance of the mismatched kidney. One eventually rejected the organ and got another; the other two have staved off rejection with continued use of immunosuppressive drugs. The remaining five achieved "complete chimerism" and a year later were weaned off their immunosuppressive drugs without incident.

Dr. David H. Sachs, a transplantation expert at Massachusetts General Hospital and author of a widely hailed recent study on chimerism, called the results "very interesting ... and very different from what others expected." But he added that they "are not going to be easy to reproduce," given the authors' choice to keep the method of cellular preparation a secret.

"We're really excited about it," Ildstad said in an interview. She said she hoped next to use the new methods to explore the transplantation of livers and pancreatic islet cells between mismatched donors and recipients.

Ildstad said the success of the study's five kidney transplant patients has implications beyond the 93,000 Americans currently awaiting a donated kidney. For some of the 12,000 patients awaiting hearts, lungs, livers and other donor organs, the regimen could point the way to improving success rates and reducing reliance on anti-rejection drugs for them as well, she said.

In addition, the authors believe their research could allow the retroactive treatment of transplant patients (mostly those with new kidneys) who are living with imperfectly matched organs — if those donors are still alive and willing to donate stem cells.

melissa.healy@latimes.com

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