BACKGROUND: Circulating nucleosomes are representative of cell death, which is a feature of acute graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT).

OBJECTIVE: We explored whether plasma nucleosome levels were prognostic for acute GVHD.

STUDY DESIGN: We examined the level of circulating nucleosomes in 131 patients who underwent a myeloablative allo-HSCT between June 2015 and August 2018. The measurements were made using quantitative photometric sandwich-ELISA on stored plasma samples obtained pre-transplantation (at a median of day -23) and around days +7, +14, and +28 after allo-HSCT.

RESULTS: The median plasma nucleosome level remained constant until day +28, where they increased significantly (p < 0.001 compared to all other times of measurement). The plasma nucleosome level at day +28 was inversely associated with the risk of later grade II-IV acute GVHD (OR 0.86 per 5 arbitrary unit (AU) increase [95% CI: 0.66-0.99], p = 0.03), also after adjustment for risk factors of acute GVHD (OR 0.78 per 5 AU increase [95% CI: 0.56-0.96], p = 0.01). We found no support for an association between the plasma level of nucleosomes measured pre-transplantation or around day +7 or +14 and the risk of subsequent grade II-IV acute GVHD. We observed a positive correlation between nucleosomes, ST2 and C-reactive protein at day +28 (Spearman's ρ = 0.522, p < 0.001; and Spearman's ρ = 0.386, p < 0.001; respectively).

CONCLUSION: A lower level of plasma nucleosomes at day +28 after HSCT was associated with a higher risk of subsequent acute GVHD. Additional studies are needed to validate circulating nucleosomes as a prognostic biomarker of acute GvHD.