Plasma Nucleosome Levels and Risk of Acute Graft-Versus-Host Disease After Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center Cohort Study.

Abstract

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). We explored whether plasma nucleosome levels were prognostic for acute GVHD. 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 pretransplantation (at a median of day -23) and around days +7, +14, and +28 after allo-HSCT. The median plasma nucleosome level remained constant until day +28, where they increased significantly (P < .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 to IV acute GVHD (odds ratio [OR] 0.86 per 5 arbitrary unit [AU] increase [95% confidence intervals (CI): 0.66 to 0.99], P = .03), also after adjustment for risk factors of acute GVHD (OR 0.78 per 5 AU increase [95% CI: 0.56 to 0.96], P = .01). We found no support for an association between the plasma level of nucleosomes measured pretransplantation or around day +7 or +14 and the risk of subsequent grade II to IV acute GVHD. We observed a positive correlation between nucleosomes, suppressor of tumorigenesis 2, and C-reactive protein at day +28 (Spearman's ρ = 0.522, P < .001; and Spearman's ρ = 0.386, P < .001; respectively). 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.