Perspective from Sergio A. Giralt, MD
January 29, 2015
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Biomarkers predicted severity of GVHD after allogeneic HSCT

Perspective from Sergio A. Giralt, MD
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A prognostic score based on the concentration of biomarkers guided risk-adapted therapy at the onset of graft-versus-host disease following allogeneic hematopoietic stem cell transplantation, according to study results.

The symptoms at the presentation of graft-versus-host disease (GVHD) often do not provide enough indication to guide therapy, James L. M. Ferrara, MD, DSc, Ward-Coleman chair in cancer medicine at Icahn School of Medicine at Mount Sinai and Ruth Heyn professor of pediatric oncology at the University of Michigan Medical School, and colleagues wrote.

“High-dose steroids is the only proven treatment for GVHD,” Ferrara said in a press release. “Those with low-risk GVHD are often over-treated and face significant side effects from treatment. Patients with high-risk GVHD are undertreated and the GVHD progresses, often with fatal consequences. Our goal is to provide the right treatment for each patient. We hope to identify those patients at higher risk and design an aggressive intervention while tailoring a less-aggressive approach for those with low risk.”

Ferrara and colleagues developed an Ann Arbor GVHD score based on the concentration of the biomarkers TNFR1, ST2 and Reg3-alpha.

Researchers collected plasma from 492 patients who had newly diagnosed acute GVHD after undergoing allogeneic hematopoietic stem cell transplantation (HSCT).

Ferrara and colleagues randomly assigned patients to the training (n=328) and test (n=164) cohorts. An additional 300 patients enrolled on trials evaluating primary therapy for GVHD were included in the validation cohort.

Overall, the cumulative incidence of non-relapse mortality in each the cohorts significantly increased as the Ann Arbor score increased (P˂.0001).

In the validation cohort, researchers defined 74 patients as having an Ann Arbor score 1, 165 as score 2 and 61 as score 3. The incidence of non-relapse mortality at 12 months was 8% (95% CI, 3-16) among those with score 1, 27% (95% CI, 20-34) among those with a score 2, and 46% (95% CI, 33-58) among those with score 3 (P˂.0001).

More patients in the validation cohort with score 1 responded to primary GVHD treatment within 28 days (86%) than patients with score 2 (67%) or score 3 (46%; P˂.0001).

“This new scoring system will help identify patients who may not respond to standard treatments, and may require an experimental and more aggressive approach,” Ferrara said. “And it will also help guide treatment for patients with lower-risk GVHD who may be over-treated. This will allow us to personalize treatment at the onset of the disease. Future algorithms will prove increasingly useful to develop precision medicine for all HSCT patients.”

Evaluating plasma biomarkers will further help target agents in this setting, Brian Betts, MD, Claudio Anasetti, MD and Joseph Pidala, MD, PhD, all from the department of blood and marrow transplantation at the Moffitt Cancer Center, wrote in an invited commentary.

“GVHD biomarker discovery is rapidly evolving,” Betts, Anasetti and Pidala wrote. “As a field, we must focus on functional and druggable targets, and ensure that the correct patient population is selected for clinical trials based on relevant biomarker expression. Levine and colleagues should be commended for their efforts in advancing these concepts.”

For more information:

Betts B. Lancet Haematol. 2014;doi:10.1016/S2352-3026(14)00040-4.

Levine JE. Lancet Haematol. 2014;doi:10.1016/S2352-3026(14)00035-0.

Disclosure: The researchers report royalties from patents on GVHD biomarkers. Betts, Anasetti and Pidala report no relevant financial disclosures.