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Identification of biomarkers may allow for better management of GVHD
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The management of graft-versus-host disease is associated with “multiple problems,” according to James L. M. Ferrara, MD, DSc, of the Icahn School of Medicine at Mount Sinai.
“What happens here at Mount Sinai is not necessarily what happens at Dana Farber in Boston or at Stanford in California,” Ferrara said, leading to a lack of guidelines that are generalizable across institutions. “Another issue is staging GVHD accurately. Most of the people who stage it are not the senior physicians who study this – they’re fellows or residents. The clinical data is often confusing and even contradictory, particularly early in the disease.”
In addition, there are no tools to aid physicians in determining prognosis.
“The clinical symptomatology – and the confusion around that – is one problem,” Ferrara told HemOnc Today. “Another major problem is the fact that we have no laboratory tests that can actually tell us who, importantly, is going to get GVHD, and, if you get GVHD, who’s going to do well and who’s going to do poorly.”
As a result, there is a need for “better markers early in the disease.”
Biomarkers may identify patients at risk for GVHD, allow for earlier treatment
Early in 2015, Ferrara and colleagues across the United States and Europe published results in The Lancet Haematology demonstrating that a prognostic score based on the concentration of biomarkers guided risk-adapted therapy at the onset of GVHD after allogeneic hematopoietic stem cell transplantation. Ferrara and colleagues developed an Ann Arbor GVHD score based on the concentration of the biomarkers TNFR1, ST2 and Reg3-alpha.
The prognostic score demonstrated that non-relapse mortality significantly increased as the Ann Arbor score increased. In addition, patients who presented with a skin rash who also had a high-risk biomarker signature were more likely to develop gastrointestinal GVHD, one of the most problematic types of GVHD, according to Ferrara. This means that clinicians “can start to see gastrointestinal GVHD before it actually occurs and intervene early,” he said.
The researchers are now working to develop a biomarker signature that can predict GVHD prior to the onset of symptoms. Ferrara and colleagues have examined the biomarker signatures in patients on day 7 following HSCT.
“This is well before most patients get acute GVHD,” Ferrara told HemOnc Today. “Ninety-five percent of the patients develop it after day 14 or 15. This is a full week before the onset of symptoms.”
The biomarker signature enabled researchers to classify patients into 2 groups, according to Ferrara: those at high risk for severe, acute GVHD and those at low risk.
“This is the first time that we can actually predict severe GVHD prior to onset,” Ferrara told HemOnc Today. “Very interestingly, the target organ that is most affected in severe GVHD is the gastrointestinal tract, and the biomarkers that are largely reflective of disease in the gastrointestinal tract – the ST2 and the REG3 Alpha – are the biomarkers that are most important in this new signature at day 7 after transplant.”
The ability to identify patients at high risk for GVHD and treat the disease based on these biomarker signatures may enable physicians to improve outcomes.
“We can now try to intervene, particularly with therapeutic strategies that would target the GI tract, to prevent this scourge from affecting our patients and increasing the obstacles to transplantation,” Ferrara said. “We think that there is now new hope for patients after allogeneic HSCT to separate this graft-versus-leukemia affect from GVHD and reduce GVHD-related mortality.” – by Julia Ernst, MS
Disclosures: Ferrara reports royalties from patents on GVHD biomarkers.