A new biomarker for therapy-resistant graft-versus-host disease and death

Image: PD

1. Patients with high suppressor of tumorigenicity 2 (ST2) levels at the initiation of graft-vs-host-disease (GVHD) therapy were more likely to have treatment-resistant GVHD and to die within 6 months of therapy initiation. 

2. Plasma ST2 values measured at day 14 after transplantation is a better predictor of death without pre-transplant disease relapse than other known risk factors. 

Evidence Rating Level: 2 (Good) 

Study Rundown: High dose glucocorticoids are the standard of care for treatment of GVHD, a common complication following allogeneic hematopoietic stem-cell transplantation. Patient response to therapy is variable, and non-responders have a higher mortality. This study marks suppressor of ST2 as a biomarker that might allow prospective identification on patients likely not to respond.

The ability to identify patients at high risk of death before the development of GVHD would allow for better clinical management and earlier interventions. While samples from patients were collected prospectively, the ability of ST2 to predict outcomes might be overestimated as prediction models were developed using retrospectively defined data sets. Further investigations with a larger population might better assess the stratifying ability of ST2.

ST2 is a recently identified interleukin-1 receptor thought to be important in switching type 2 helper (TH2) cells towards type 1 helper (TH1) cell behavior, which might be important in the pathogenesis of GVHD.

Click to read the study, published today in NEJM

Relevant Reading: Graft-versus-Host Disease Treatment: Predictors of Survival

In-Depth [prospective cohort study]: Patients with GVHD (n=381) were divided into two groups on the basis of response status to glucocorticoids at day 28. Patients with high ST2 values at initiation of therapy were found to be 2.3 times as likely to have treatment-resistant GVHD compared to those with low ST2 values (95% confidence interval, 1.5 to 3.6).

The survival difference between patients with high GVHD grade and low ST2 concentration and patients with low GVHD grade and high ST2 concentration was 53% (p<0.001), indicating that the biomarker value was more important than clinical grade in predicting outcome.

ST2 concentrations were measured on day 14 after transplantation in 94 patients with no GVHD and 208 patients who subsequently developed grade I to IV GVHD, and also in an independent set of 75 patients. A high ST2 concentration on day 14 after transplantation was significantly associated with an increased six-month risk of mortality without relapse of pre-transplant disease.

By Xu Gao and Mitalee Patil

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