Blood biomarker may help diagnose GVH disease of the skin

Measuring levels of elafin, a plasma biomarker specific for graft-versus-host disease, enabled physicians to identify which patients who received bone marrow transplants and subsequently developed skin rashes had GVH disease of the skin.

Rashes in patients who had bone marrow transplants may indicate GVH disease, although a firm diagnosis is not easy and, currently, the only reliable way to determine the cause of the rash is skin biopsy, according to researchers.

To identify a key biomarker of GVH disease of the skin, the researchers evaluated elafin, an alarm antiprotease secreted in response to interleukin-1 and tumor necrosis factor alpha, as a biomarker in 492 patients who had allogeneic bone marrow transplant.

Concentrations of elafin were 3.9 times higher in patients with GVH disease compared with those with a non-GVH rash (P<.001).

“This blood test can determine the risk a patient may have for further complications, and thus physicians will be able to adjust therapy to the degree of risk, rather than treating every patient in exactly the same way,” said James Ferrara, MD, Ruth Heyn Endowed Professor of Pediatrics and Communicable Diseases and director of the bone marrow transplant program at the University of Michigan.

“For example, patients at low risk do not need to have additional medicine to further suppress their immune systems. Or patients with high levels who do not respond rapidly to standard treatment could be treated with additional therapy.”

In a validation set based on clinical symptoms, patients with skin GVH disease had elafin levels that were twice as high as patients without GVH disease; patients with isolated gastrointestinal GVH disease; and patients with a skin rash that was not GVH (P<.001).

In addition, as the stage of disease increased, elafin levels rose. Levels were higher in patients with GVH disease rashes than in patients with non-GVH rashes for stage II and stage III to IV disease (P<.001).

The researchers then divided patients according to elafin concentration using the median concentration as the cutoff. At one year, the nonrelapse mortality rate was higher among patients with elafin levels 6,000 pg/mL or greater vs. patients with elafin levels less than 6,000 pg/mL (28% vs. 11%; P=.06).

Those with high levels of elafin died from GVH disease more often than those with low levels (26% vs. 8%; P=.02). OS at five years was 48% in the low-level group vs. 26% in the high-level group (P=.01).

In an analysis adjusted for other known prognostic factors, high elafin levels at the time of diagnosis maintained their association with an elevated risk for death (HR=1.71; 95% CI, 1.08-2.69).

Paczesny S. Science Translational Medicine. 2010;doi:10.1126/scitranslmed.3000406.

The interesting thing about the findings of this study is it appears there seems to be specificity with organ site. As a transplantor, I believe biomarkers of GVH disease are definitely needed, not only to make decisions about patient therapy, but also for better study of novel agents to treat GVH disease. My impression is that pathologic diagnosis of GVH disease is not always perfect, is not amenable to accurately measure response and if we had some other way to make a clinical decision - especially in biopsies which are somewhat equivocal - it would certainly be an asset to the field.

- Jeffrey Miller, MD
HemOnc Today Editorial Board member