Check Up: Innovation in stem-cell donation

Posted: September 19, 2011

When all other treatments fail, deadly blood disorders can be cured by destroying the patient's own blood system, then regenerating it with blood stem cells from a healthy donor.

But if the patient and donor lack closely matched immune system markers, the transplanted cells become a threat, attacking rather than revitalizing their new host.

Now, Thomas Jefferson University researchers have developed a way to make stem-cell transplants work, even when only half the immune markers are matched.

The advance, a goal of research around the world, has big implications. Fewer than half of white people and only 10 percent of minority groups can find closely matched stem-cell donors among siblings or registries of volunteers. "Half-match" transplants would triple the pool of suitable donors, giving new hope to patients with terminal leukemia, lymphoma, sickle-cell anemia, and other blood diseases, said Dolores Grosso, lead author of a Jefferson study published online in the journal Blood. "You could help almost everybody," she said.

Jefferson's innovation involves separating two donated blood components that are normally given to the patient all at once after radiation and chemotherapy kills the diseased blood supply.

One component contains the stem cells that give rise to mature blood cells.

The other component contains "T cells." These are the first line of defense against germs and tumors, so they protect transplant patients from infection and cancer recurrence. But in half-match transplants, donated T cells also attack the patient's tissues, activated by unfamiliar immune markers.

Grosso and Neal Flomenberg, Jefferson's head of oncology, knew the aggressiveness of T cells varies. They theorized that giving a low dose of T cells, followed by chemotherapy to kill off the most active ones, would leave just enough to fight infection and cancer recurrence.

It worked. In the first clinical test of 27 patients, 48 percent survived three years. In contrast, fewer than 20 percent of patients survive conventional half-match transplants.

"I did my first half-match transplant in the early 1980s. There was always one more problem to fix to make this work well," Flomenberg said. "I feel like it's the cherry on the sundae of my career."

- Marie McCullough

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