High day 28 ST2 levels predict for acute graft-versus-host disease and transplant-related mortality after cord blood transplantation

Abstract

While cord blood transplantation (CBT) is an effective therapy for hematologic malignancies, acute graft-versus-host disease (aGVHD) is a leading cause of transplant-related mortality (TRM). We investigated if biomarkers could predict aGVHD and TRM after day 28 in CBT recipients. Day 28 samples from 113 CBT patients were analyzed. Suppressor of tumorigenicity 2 (ST2) was the only biomarker associated with grades II-IV and III-IV aGVHD and TRM. Day 180 grade III-IV aGVHD in patients with high ST2 levels was 30% (95% confidence interval [CI], 18-43) vs 13% (95% CI, 5-23) in patients with low levels (P = .024). The adverse effect of elevated ST2 was independent of HLA match. Moreover, high day 28 ST2 levels were associated with increased TRM with day 180 estimates of 23% (95% CI, 13-35) vs 5% (95% CI, 1-13) if levels were low (P = .001). GVHD was the most common cause of death in high ST2 patients. High concentrations of tumor necrosis factor receptor-1, interleukin-8, and regenerating islet-derived protein 3-α were also associated with TRM. Our results are consistent with those of adult donor allografts and warrant further prospective evaluation to facilitate future therapeutic intervention to ameliorate severe aGVHD and further improve survival after CBT.

Figure 1

Day 28 landmark analysis of grade III-IV aGVHD according to day 28 ST2 level. Patients who engrafted and were without grade II-IV aGVHD at day 28 were included in the analysis (n = 106). Elevated day 28 ST2 was associated with a significantly increased risk of subsequent severe aGVHD.

Figure 2

Day 28 landmark analysis of TRM according to day 28 ST2 level in 113 DCBT recipients. DCBT recipients with elevated day 28 ST2 had a significantly increased risk of TRM.