Biomarker predicts immune response after stem cell transplants

A biomarker accessible in blood tests has been identified and validated. It could be used to predict which patients who have received stem cell transplants are at the highest risk for the potentially fatal immune response of graft-versus-host disease (GVHD).

Although transplant specialists have been able to reduce its impact, GVHD remains a leading cause of death among patients who receive a stem cell transplant from another person, which is known as an allogeneic transplant. Such transplants are used to treat blood and bone marrow cancers such as leukemia and multiple myeloma, often as a last resort. GVHD occurs when immune cells from the transplant “see” the patient's body as foreign and attack it.

Approximately 20,000 allogeneic stem cell transplants were performed worldwide in 2012. Among stem cell transplant recipients whose donor is related, 30% to 40% will experience GVHD, and this percentage could rise to 60% to 80% if the patient and donor are not related.

The researchers found that patients with a high level of a protein named ST2 were more than twice as likely to have GVHD that resisted standard treatment with steroids, and nearly four times as likely to die within 6 months of the transplant. Their findings were reported in the New England Journal of Medicine (2013; 369:529-539).

"What we found particularly significant was that this marker was a better predictor than the clinical severity of the disease when it was diagnosed," said senior author Sophie Paczesny, MD, PhD, associate professor of medicine at the Indiana University School of Medicine in Indianapolis.

Thus, patients with low ST2 levels were more likely to respond to treatment regardless of how serious their GVHD was graded, while patients with high ST2 levels were less likely to respond to treatment, whether their disease was graded less serious or more serious.

"This blood test, which is currently available to clinicians, will make informed treatment possible, as the clinicians will now be able to adjust therapy to the degree of risk rather than treating every patient the same way," Paczesny said.

In addition, while the disease most commonly appears about 30 days after the transplant, higher ST2 levels in blood samples taken as early as 14 days after transplant—far before the clinical signs of GVHD are apparent—were associated with an increased risk for death from the toxicity of the transplant.

Therefore, the authors noted, early identification of patients who likely will not respond to standard treatments is important and would allow physicians to consider additional therapies and early intervention. On the other hand, patients with low risk will not need to have additional medicine further suppressing their immune system. But, they cautioned, additional large prospective studies are needed to better define the levels of risk predicted by the ST2 marker.
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