To the best of our knowledge, our study is the first one observing the preliminary efficacy and safety profile of R-slit-EPOCH plus HD-MTX in untreated DLBCL with MYC rearrangement or double expression of MYC and BCL-2. In the current study, the regimen of R-slit-EPOCH plus HD-MTX gave a relatively high response rate and yielded promising survival. This evidence concerns the gene MYC and diffuse large B-cell lymphoma.