WASHINGTON - Bone marrow transplants are one of cancer care's striking successes, but they have a dark side: The transplanted cells can turn on patients, attacking their skin and organs.
The potentially deadly side effect with the unwieldy name of graft-versus-host disease, or GVHD, strikes several thousand each year. The last decade has brought little progress in battling it.
Last month brought another blow, as the Food and Drug Administration rejected the new drug closest to market.
But that drug, called orBec, isn't dead; its manufacturer is pledging additional research to satisfy FDA's concerns. And it joins a list of other promising experiments into ways to ease the misery - from novel stem-cell infusions to drugs that block immune cells-run-amok.
The burst of research comes none too soon, as a long-lasting form of GVHD is on the rise.
'I love my doctors, but they throw up their hands. They don't know what to do,' said Stephen Dugan, 54, of Radnor, Pa., who longs for an alternative to the problematic steroid that is today's treatment mainstay.
His transplant four years ago saved Dugan from cancer. But two months later he barely survived a harsh bout of GVHD; now he battles a less severe but chronic form of the disease.
When someone receives a transplanted organ, the big fear is that their own immune system will attack the new 'foreign' tissue. GVHD is the opposite problem.
It occurs when patients receive donated bone marrow or the stem cells that produce it, pieces of someone else's immune system. Sometimes the donor's T cells, whose job is to hunt foreign invaders, become super-aggressive and attack the recipient's body.
It happens in at least half of the more than 6,000 Americans who receive allogeneic - or donated - marrow or stem-cell transplants every year. Many times, GVHD is mild or moderate, causing skin rashes or blistering, vomiting, liver or lung damage. But one of every five cases is life-threatening. A particularly dangerous form ravages the stomach and intestines, causing unremitting vomiting and diarrhea.
The only treatment: Super-high doses of the steroid prednisone for weeks, to suppress out-of-control immune cells and the inflammation they cause. But the treatment's side effects are severe, even deadly: Patients fall prey to infections; it debilitates bone and muscle until some become bedridden; and it can cause violent mood swings. Plus, about half of seriously ill patients fail to improve, prompting doctors to frantically add other steroids.
'They're our best friends but our greatest enemies,' is how Dr. Steven Pavletic of the National Institutes of Health describes prednisone and its cousins.
Now in advanced testing are treatments that aim to calm GVHD without that body-wide steroid toxicity:
n OrBec is a milder kind of steroid, a pill version of the beclomethasone that asthma patients have long inhaled.
n The experimental drug Prochymal aims to soothe the source of GVHD's inflammation without suppressing immunity.
n Johns Hopkins University researchers are studying if two doses of an old cancer drug, cyclophosphamide, at the time of transplant could prevent GVHD anywhere in the body.