Partial marrow transplants open new hopes

Bone marrow transplant researchers are easing the risks and aiming not only at cancer but diseases such as sickle-cell anemia and deadly metabolic disorders.

Beyond cancer to sickle-cell anemia and other disorders

Bone marrow transplant researchers are easing the risks so the transplants can target not only cancer but diseases such as sickle-cell anemia and deadly metabolic disorders.

The old way: High doses of radiation and chemotherapy wipe out a patient's bone marrow, then someone else's marrow replaces it, hopefully before infection strikes. 

'It makes it possible for anyone who has a mom or dad willing to donate marrow to them to have a transplant. '— Dr. Suzanne Ildstad

The new way: Rather than destroying the patient's bone marrow, just tamp it down enough to make space for donated marrow, and a sort of twin immune system takes root.

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 United States.

Wider donor pool

The ultimate hope 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 them to have a transplant," says Ildstad, who has families with sickle-cell anemia and other 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.

Doctors have long known that a traditional bone marrow transplant can cure young children of sickle-cell anemia — if they have a well-matched donor. New marrow produces healthy red blood cells to replace the sickle-shaped ones that can't squeeze through small blood vessels, the cause of the disease's pain, infections and life-threatening organ damage.

But only about 17 per cent of children have a suitable donor, usually a healthy sibling. And attempts at transplants have failed in adults, their bodies too ravaged from years of the disease.

Another hurdle is that certain immune cells in donated marrow sometimes become too aggressive and attack the recipient in a condition called graft-versus-host disease or GVHD.

Hope for sickle-cell adults

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 immune reactions, had their sickle-cell anemia apparently eliminated, Dr. John Tisdale and colleagues at the National Institutes of Health reported in December. These patients developed a hybrid immunity that produces normal red blood cells with no GVHD.

But those people had perfectly matched donor cells provided by healthy siblings. Few patients do.

Back in Louisville, Ildstad gives donated marrow a boost to try to overcome that problem while avoiding GVHD, a risk that worsens with mismatched donors. She removes troublesome immune cells from the donated infusion, leaving concentrated blood-producing stem cells that patients need, plus "facilitating cells" that she discovered seem to help them take root.

The method so far has worked in two children with sickle-cell anemia who had well-matched donors, and in one of four with a half-match.

Kidney transplants smoothed

Dr. Joseph Leventhal of Northwestern University gave an Ildstad-treated stem cell infusion to a handful of kidney transplant recipients, and they developed hybrid immune systems that seem to be holding nearly a year later.

"We're doing this in patients where it could have potentially the biggest impact," those with unrelated donors, says Leventhal.

The attraction to families: "You don't die from the new way," is how Bob Evanosky of Aurora, Ill., puts it.

His three sons have a devastating metabolic disease called metachromatic leukodystrophy, or MLD. Last summer, son John got an experimental outpatient transplant — a far cry from the months his brother Jack had to spend in intensive care after a well-matched transplant the old-fashioned way.

Dad was John's donor even though he's only a half-match, and the new cells are making the enzyme his body had lacked, too late to reverse brain damage that has paralyzed the eight-year-old boy but perhaps able to ease complications, says Evanosky, who plans to donate this fall to John's twin, Christopher.