Aggressive B-cell lymphoma with double/triple translocations involving – double/triple hit lymphoma

Abstract

Large B-cell lymphoma with cytogenetically detected rearrangement and/or increased copy number of MYC, BCL2, and/or BCL6 are frequently termed double/triple hit lymphoma (DHL/THL) due to molecular, biologic, and clinical similarities. In particular, patient outcome after standard therapy is disappointing; there is a high risk of central nervous system involvement, and resistance to second-line treatment in case of recurrent or progressive disease. DHL/THL are not recognized as a separate diagnostic entity, and should be diagnosed within the category of B-cell lymphoma unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (BCLU). In majority of cases, DHL/THL display molecular and phenotypic features of GCB (germinal center B-cell-like) cell of origin. There is also a distinct group of large B-cell lymphoma with overexpression of MYC (usually ≥40% cells positive), BCL2, and/or BCL6 (usually ≥50–70% cells positive), called double expressor (DE). These cases are in majority derived from non-GCB/ABC cell of origin. Similar to the DHL, prognosis in DE is poor, and second-line therapy in case of relapse or progression is unsuccessful. Limited, available clinical data suggest that a standard immunochemotherapy R-CHOP is unacceptable for both DHL and DE, and new approaches to therapy and new drugs are needed.