Treatment Allows Drug-Free Transplant Patients to Elude Graft-versus-Host Disease

Posted: March 8, 2012 at 1:08 am

Nature | Health

Bone-marrow transfers prior to organ transplants could end the need for lifelong immunosuppression

March 7, 2012

By Elie Dolgin of Nature magazine

Graft-versus-host disease (GvHD) is a common and often deadly complication of bone-marrow transplantation that occurs when immune cells from an unrelated donor attack the transplant recipient's tissue. Now, researchers have for the first time managed to completely replace people's bone-marrow-derived stem cells with those from unrelated donors without causing GvHD. And because of this, the recipients could also accept kidneys from the same donors without the need for drugs that suppress the immune system.

"The outcome has been amazing," says Lindsay Porter, a 47-year-old Chicago resident with polycystic kidney disease who was one of the study subjects. She has been off immunosuppressive drugs for seven months. "I feel so normal, it feels like it's not a big deal."

But according to experts in the field, the findings, published today in Science Translational Medicine, are a huge deal. "It's kind of difficult to believe," says Tatsuo Kawai, a transplant surgeon at Massachusetts General Hospital in Boston, who wrote a commentary to accompany the paper. "It's almost common sense to have GvHD in mismatched individuals."

Facilitating tolerance

The latest study builds off of work Kawai and his colleagues began fourteen years ago, when they launched the first clinical trial that attempted to use bone marrow to induce immune tolerance for kidney recipients, to avoid the sometimes dangerous side effects of life-long immosuppressive therapy.

Working first in people with perfectly immune-matched siblings and then with partially mismatched donor-recipient pairs, the researchers showed that the majority of individuals could achieve stable kidney function and successfully wean off of their immunosuppressants with few problems -- in one case for up to nine years. But the study subjects only maintained noticeable levels of the foreign bone marrow for a few weeks, and the protocol didn't work for everybody. Some researchers speculated that maintaining higher levels of donor immune cells for longer could help to improve the success rate.

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Treatment Allows Drug-Free Transplant Patients to Elude Graft-versus-Host Disease

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