By giving kidney transplant patients a dose of donor bone marrow, researchers have for the second time enabled a majority of recipients to stop taking immune suppressants despite having received poorly matched organs.
The new study, in the March 7 Science Translational Medicine, accomplished the feat in five of eight transplant recipients who weren’t spot-on matches with their donors. The five tapered off suppressants designed to prevent organ rejection and have stayed free of the drugs for at least six months. One is nearly two years out since quitting the medicines, researchers at the University of Louisville in Kentucky and Northwestern University School of Medicine in Chicago report.
Previously, a team at Harvard Medical School pulled this off in mismatched kidney transplants using a different procedure. Among 10 patients, seven recipients in that study have been able to stop immune suppression for up to nine years.
For nearly everyone living with mismatched donor kidneys, the idea of chucking antirejection medicine is a tantalizing but faint hope. Typically, all must keep up the meds for the rest of their lives.
Both new techniques harness chimerism to help engender tolerance to the transplants. In Greek mythology, a chimera was a creature with parts from several different kinds of animals. In the human immune system, chimerism requires contributions from just two people — a donor and a recipient — but mixing immune systems is asking for trouble. The recipient might react against the donor organ (which is what happens in rejection), or donor immune cells in the transplant might declare war on their new host (what’s called graft-versus-host disease). But properly achieved, chimerism might actually prevent hostilities.
In the new study, researchers altered the normal transplant routine. They took bone marrow stem cells from the kidney donor before the transplant and processed these cells, which give rise to nascent immune cells, with what they call “facilitator cells.” The facilitator cells, whose exact identity and function is shielded due to patent considerations, are designed to make the marrow cells more agreeable to transplant, says study coauthor Suzanne Ildstad, a transplant surgeon at the University of Louisville. In recipients given the specially processed donor marrow along with their transplant, donor T-regulatory cells — which apparently tone down the donor immune system’s attack potential — might play an enhanced role in the months post-transplant, she says.
Transplant recipients in the new study received radiation and chemotherapy beforehand to prepare for the donor bone marrow. After the transplant, the patients were gradually tapered off immune suppressants over a year. In the five who succeeded — or, as the researchers put it, achieved “durable chimerism” — the donor marrow cells had spawned a complete replacement immune system. Data show no sign of the recipients’ original immune cells.
“It’s a remarkable feat,” says David Sachs, a transplant surgeon at Harvard Medical School in Boston who coauthored the earlier study. That team’s strategy, which also used bone marrow stem cells, induced temporary, weeks-long immune chimerism that seemed adequate to induce long-term tolerance in the patients, says Tatsuo Kawai, a transplant surgeon at Harvard who coauthored that work.
The new findings are surprising and even amazing, they both acknowledge, but since the technique is proprietary, “it will be hard to reproduce,” Sachs says.