Although there is no widely accepted standard approach to manage HGBL with MYC and BCL2/BCL6 rearrangements, retrospective comparisons show that DHL cases do better when treated with dose-intensive approaches compared to R-CHOP, like dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, hydroxydaunorubicin, and rituximab (DA-EPOCH-R), or cyclophosphamide, doxorubicin, vincristine, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (R-CODOX-M/R-IVAC). This evidence concerns the gene BCL2 and high grade B-cell lymphoma.