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Blood Test Developed for Deadly Transplant Complication

6 January 2010 (All day)
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S. Paczesny et al., Science

Telltale sign. The production of elafin (stained brown) by top-layer skin cells distinguishes skin GVHD from other kinds of rash.

Researchers have developed a new blood test to diagnose and predict the severity of graft-versus-host disease (GVHD), an often deadly complication that strikes people who have received bone marrow transplants for cancer or other conditions. The test could help physicians decide more quickly which patients need critical treatment.

GVHD is the equivalent of organ rejection syndrome for bone marrow transplant patients. The disease starts when the immune cells in donor bone marrow identify the recipient's cells as foreign and launch an attack. The initial clinical symptom is often a skin rash, which sometimes makes early diagnosis difficult. But if allowed to progress, the disease can damage the internal organs and proves fatal in 30% to 40% of cases. Apart from relapse of a person's disease, GVHD is the principal cause of death in patients who have received donated bone marrow.

Because of the severity of GVHD, clinicians often begin treatment--high doses of steroids to suppress the immune response--in the absence of a concrete diagnosis. But this preemptive strategy can also be dangerous, raising the risk of infections and possibly increasing the chance of relapse in cancer patients. "There is a sense that we are overtreating some patients and undertreating others," says pediatric oncologist and study co-author James Ferrara of the University of Michigan, Ann Arbor.

To aid early diagnosis, Ferrara's team took weekly plasma samples from patients who had received donated bone marrow. They compared levels of elafin--an anti-inflammatory protein produced by the body in response to skin GVHD--in 10 patients who had developed the disease and 20 patients who had not. On average, elafin levels in patients developing skin GVHD were three times higher, the researchers report online today in Science Translational Medicine.

Next, the researchers divided 159 patients with the disease into two groups--those with higher than average plasma levels of elafin and those with lower than average levels--and followed each group's long-term survival. After 12 months, three times as many patients in the high-elafin group had died from GVHD and its complications than in the low-elafin group. "In the future, we hope a clinician might be able to test the elafin levels of a transplant patient with a rash to decide whether to initiate treatment," says Ferrara. If, as the researchers suspect, elafin levels rise before GVHD symptoms develop, it might also be possible to identify patients at risk who have no rash.

Hematological oncologist Corey Cutler of Harvard Medical School in Boston notes that GVHD can frequently be diagnosed just by close examination of skin rashes, but a more definitive diagnostic test would be welcome. "If this test could predict the onset of GVHD before the rash develops, it could be extremely valuable," he says.

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