First Bari Martz's fingers turned blue. Then she started gasping for breath, and her joints stiffened so that she couldn't even open her hands. Doctors diagnosed scleroderma, part of an insidious family of diseases where the immune system attacks a patient's own body, sometimes enough to kill.
Worsening rapidly, the Florida woman took a gamble: Doctors stored stem cells from her blood and then wiped out her faulty immune system. Her reinfused stem cells seem to have let a healthy new immune system take root, stopping more damage and, nearly two years later, letting her lungs and joints heal enough for better function.
Studies here and in Europe are aiming to reset immunity for patients with severe scleroderma — work that, if successful, could cast new light on numerous autoimmune diseases, from lupus to multiple sclerosis.
While early reports are promising, it remains experimental, recruitment is slow and a fundamental issue is unsettled: Do doctors need to take the radical step of killing all the bad immune cells, or just suppress their function?
"The notion that more immunosuppression is better is somewhat logical," says Dr. Ellen Goldmuntz of the National Institutes of Health, which is funding some of the research. "The question's how best to do it."
Autoimmune diseases are among medicine's most frustrating mysteries: What makes an immune system that worked fine for years suddenly run amok, and why are middle-aged women most vulnerable? And arguably most mysterious is scleroderma, where the immune system somehow mistakenly attacks connective tissues that support the skin and internal organs — thickening skin, stiffening joints, destroying blood vessels, and sometimes killing through kidney and lung failure.
About 300,000 Americans have various forms of scleroderma, often confined to the skin. But a third have systemic scleroderma, the most severe form that invades internal organs. Only the cancer drug cyclophosphamide is proven to slow severe scleroderma, but its effects are modest. About half of severely affected patients die in five years.
Enter stem cell transplants. Similar to a bone marrow transplant, it's a risky treatment usually reserved for leukemia. A type of stem cell that generates immune-system cells is culled from patients' blood, and then radiation or chemotherapy or both destroy circulating immune cells — leaving the person vulnerable to life-threatening infections until the stem cells are returned and produce again.
Why would reinfusing a patient's own stem cells help? The theory is that someone genetically predisposed to certain autoimmune diseases stays healthy until something in the environment triggers misfiring immunity — meaning stem cells shouldn't be diseased, explains Dr. Keith Sullivan of Duke University, who is leading the largest study of the transplants, called the SCOT trial.
About 30 hospitals in the U.S. and Canada are recruiting 226 patients with severe scleroderma to be randomly assigned either the stem cell transplant or a year of cyclophosphamide at doses 50 percent higher than is standard today.
A pilot study of nearly three dozen scleroderma patients, published last year, counted eight transplant-related deaths, teaching researchers to take some extra safety steps including shielding lungs and kidneys during radiation. Still, 64 percent of transplant survivors got no worse for a median of four years and counting — and some had remarkable healing of damaged skin and lungs.
In-depth looks at a few transplant recipients show immune cells can "come back in a reprogrammed and normalized way," Sullivan says. Researchers recently reported a regrowth of blood vessels once thought impossible.
"There wasn't a choice," Martz, now 49, of Parkland, Fla., says of volunteering for the SCOT trial. She was losing about 10 percent of lung function a month, and feared she had less than a year left to live when she underwent her January 2007 transplant. "If I died from it, well, at least I went out fighting."
For now, "I'm great," she says. Her lung function jumped and is still improving, she can flex her hands again, and can even climb stairs, if slowly. "I'm continuing to get better."
A similar scleroderma study is under way in Europe; smaller pilots in lupus and a few other autoimmune diseases have signaled promise; and other U.S. researchers are trying stem cell transplants as a boost to a suppressed, not destroyed, immune system.
One hurdle to finishing these studies and learning if the approach really works: Transplants cost $125,000 to $175,000, and while some insurers pay for patients enrolled in government-certified studies, others won't. Martz's primary insurer in Florida refused; a backup policy from her husband, a retired New York police officer, did pay.