{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T03:51:59Z","timestamp":1777521119634,"version":"3.51.4"},"reference-count":96,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,12,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The high-grade B-cell lymphomas represent a pathologically and clinically heterogeneous group of mature B-cell malignancies. With modern molecular diagnostics and genomic studies, they are becoming increasingly resolved as we understand more of their shared oncogenic mechanisms. The result has been a realignment of the classification of these tumors, which may initially appear baffling. These tumors are most commonly of large cell morphology but can be of variable high-grade morphology. The double-hit high-grade B-cell lymphomas (HGBLs) that harbor dual translocations of MYC and BCL2 are of a germinal center phenotype and have a homogeneous biology. By contrast, those with dual MYC and BCL6 translocations do not appear to have such a unifying biology. The group of HGBLs not otherwise specified is poorly resolved and not characterized by distinct oncogenic aberrations. Together, the HGBLs may present with aggressive features; respond poorly to R-CHOP, ie, rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone; and may benefit from intensified induction regimens. However, clinical interpretation is hampered by a paucity of prospective studies. In the relapsed and refractory setting, chimeric antigen receptor T-cell therapy has demonstrated significant efficacy, and there is much expectation for other novel therapeutic approaches, including bispecific antibodies. By understanding the biology and a commitment to collaborative prospective evaluation, their high diagnostic and treatment challenges may be resolved.<\/jats:p>","DOI":"10.1182\/hematology.2025000749","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T14:09:59Z","timestamp":1764943799000},"page":"555-563","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":1,"title":["High-grade B-cell lymphomas: high difficulties to\u2009diagnose and treat?"],"prefix":"10.1182","volume":"2025","author":[{"given":"Andrew J.","family":"Davies","sequence":"first","affiliation":[{"name":"School of Cancer Sciences, University of Southampton, Southampton General Hospital, Southampton, 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