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Easing Bone Marrow Transplants Key To Greater Adaption

Tue, 05/11/2010 - 5:39am

Lauran Neergaard, AP

Bone marrow transplants are undergoing a quiet revolution: No longer just for cancer, research is under way to ease the risks so they can target more people with diseases from sickle cell to deadly metabolic disorders.

The old way: High doses of radiation and chemotherapy wipe out a patient's own bone marrow before someone else's is infused to replace it, hopefully before infection strikes.

The new way: Rather than destroying the patient's bone marrow, just tamp it down enough to make space for the donated marrow to squeeze in alongside and a sort of twin immune system takes root. It's what doctors taking a page from mythology call “mixed-cell chimerism” – patient and donor blood and immune cells living together to improve health.

To find the best methods for these less intense transplants, different mixes of low-dose radiation and immune-suppressing drugs are under study at hospitals around the country. But the ultimate quest is to allow transplants even when donors aren't a good genetic match, says Dr. Suzanne Ildstad of the University of Louisville – whose technique involves an experimental tweaking of donated cells to help them grow better.

“It makes it possible for anyone who has a mom or dad willing to donate marrow to have a transplant,” says Ildstad, who has families with sickle cell and other childhood genetic illnesses lining up to try.

Separately, several hospitals are testing how to combine kidney transplants with bone marrow transplants from the same donor, in hopes that a hybrid immune system lessens the need for lifelong anti-rejection drugs.

“People are watching with eager expectation,” says Dr. Lakshmanan Krishnamurti of Children's Hospital of Pittsburgh, who is helping to plan a multi-hospital study of some of the new methods for hard-to-treat adults with sickle cell disease.

Doctors have long known that a traditional bone marrow transplant can cure young children of sickle cell if they have a well-matched donor. But only about 17 percent of children have a suitable donor, usually a healthy sibling. Attempts to transplant adults have failed, their bodies too ravaged from years of the disease. Another hurdle: Certain immune cells in donated marrow sometimes become too aggressive and attack the recipient.

Enter the new research. First came a tantalizing success in severely ill adults. Nine of 10 patients who underwent a less intense transplant using low-dose radiation and two drugs to inhibit problem immune reactions had their sickle cell apparently eliminated, reported Dr. John Tisdale and colleagues at the National Institutes of Health in December. They developed a hybrid immunity that produces normal red blood cells with no rejection effects. But those people had perfectly matched donor cells provided by healthy siblings. Few patients do.

Back in Louisville, Ildstad removes troublesome immune cells from the donated infusion, leaving concentrated amounts of the blood-producing stem cells patients need, plus “facilitating cells” that she discovered to help them take root.

In an NIH-funded experiment at Louisville and Duke University, the method worked in two children with sickle cell who had well-matched donors and one of four with a half-match.

Dr. Joseph Leventhal of Northwestern University gave an Ildstad-treated stem cell infusion to a handful of kidney transplant recipients who developed hybrid immune systems that seem to be holding nearly a year later. The first three treated are using one anti-rejection drug instead of the usual cocktail, and one soon will attempt full weaning.

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