Study design and an overview of the 5hmC-Seal assay. A total of 48 cfDNA samples collected at the time of diagnosis from patients with DLBCL is included in this study. A weighted prognostic score based on the 5hmC marker genes is developed to evaluate prognosis after treatment. The 5hmC-Seal technique uses a chemical labeling strategy to sensitively profile 5hmC in cfDNA from nanogram-level DNA materials. *Clinical outcomes, including the development of clinical events (ie, relapse, death) are missing for 2 patients.