A six-protein biomarker panel predicted mortality and response to GVHD therapy.
A limiting factor in allogeneic hematopoietic cell transplantation is the development of graft-versus-host disease (GVHD). Having the ability to predict response to GVHD-treatment and survival might improve transplant outcomes.
To achieve this goal, investigators collected serum from 112 patients with newly diagnosed acute GVHD and evaluated six biomarkers: tumor necrosis factor receptor-1, interleukin-2-receptor-α, interleukin-8, hepatocyte growth factor, regenerating islet-derived 3-α, and elafin (a skin-specific marker). The relative effects of each biomarker were summarized, and a threshold was set for defining high versus low biomarker panel values.
Results were as follows:
- Individuals with high biomarker panel values (32 patients) versus low values (80 patients) at inception experienced worse 180-day mortality (56% vs. 21%; odds ratio, 4.76; P<0.0001).
- High panel values at inception independently predicted 180-day mortality after adjustment for onset of GVHD grade (II/IV vs. I/II), relatedness of donor, and stem cell source (OR, 4.61; P<0.001).
- High panel values at inception predicted nonresponse to GVHD therapy at day 28 after adjustment for onset of GVHD grade (OR, 2.98; P=0.017).
- Patients with high panel values at day 14 were more likely to be nonresponsive to treatment at day 28 (56% vs. 17%; OR, 6.32; P<0.001).
- Patients with high panel values at day 28 experienced worse 180-day mortality (49% vs. 87%; OR, 7.22; P<0.0001).
- Including panel values at day 28 with other predictors of 180-day mortality provided an additional independent predictor (OR, 7.43; P<0.001).
Comment: Acute GVHD is a major factor affecting the survival of patients following allogeneic transplantation. Because steroids and other agents affect the course of the disease in various ways, predicting outcome in individual patients has been difficult. If the biomarker panel described by these authors is validated in a more heterogeneous clinical sample, it will be helpful in managing this challenging disorder.