Daniel J Landsburg1, Adam M Petrich2, Jeremy S Abramson3, Aliyah R Sohani4, Oliver Press5, Ryan Cassaday5, Julio C Chavez6, Kevin Song7, Andrew D Zelenetz8, Mitul Gandhi2,9, Namrata Shah10, Timothy S Fenske10, Jesse Jaso11, L Jeffrey Medeiros11, David T Yang12, Chadi Nabhan13. 1. Division of Hematology/Oncology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. 2. Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois. 3. Center for Lymphoma, Massachusetts General Hospital Cancer Center, Boston, Massachusetts. 4. Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. 5. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. 6. Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, Florida. 7. Leukemia/BMT Program of British Columbia, British Columbia Cancer Agency, Vancouver, British Columbia, Canada. 8. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. 9. Virginia Cancer Specialists, Fairfax, Virginia. 10. Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin. 11. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. 12. Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin. 13. Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, Illinois.
Abstract
BACKGROUND: Double-hit lymphomas (DHLs) are collectively defined as B-cell non-Hodgkin lymphomas harboring rearrangements of MYC as well as B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6). To the authors' knowledge, the impact of specific oncogene rearrangements on outcomes of patients with DHL who are treated with immunochemotherapy has not been previously described. METHODS: The authors identified patients whose diagnostic tissue specimens underwent metaphase karyotyping or fluorescence in situ hybridization for MYC as well as both BCL2 and BCL6 rearrangements. Cohorts were defined by the presence (+) or absence (-) of rearrangements: MYC+/BCL2+/BCL6- (BCL2-DHL), MYC+/BCL2-/BCL6+ (BCL6-DHL), and MYC+/BCL2+/BCL6+ (triple-hit lymphoma; THL). RESULTS: A total of 117 patients were included in the current analysis (76 BCL2-DHL patients, 16 BCL6-DHL patients, and 25 THL patients). Compared with patients with BCL2-DHL, those with BCL6-DHL were more likely to be classified as having a non-germinal center cell of origin, presented with extranodal disease, and appeared to achieve higher rates of complete response despite receiving intensive induction therapy less frequently. However, patients with BCL6-DHL experienced a shorter median overall survival if achieving an initial complete response compared with patients with BCL2-DHL. Patients with THL experienced survival outcomes similar to those of patients with BCL2-DHL. CONCLUSIONS: Recognition of the specific oncogene rearrangements may be of prognostic value and potentially guide future therapeutic strategies for patients with DHL.
BACKGROUND: Double-hit lymphomas (DHLs) are collectively defined as B-cell non-Hodgkin lymphomas harboring rearrangements of MYC as well as B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6). To the authors' knowledge, the impact of specific oncogene rearrangements on outcomes of patients with DHL who are treated with immunochemotherapy has not been previously described. METHODS: The authors identified patients whose diagnostic tissue specimens underwent metaphase karyotyping or fluorescence in situ hybridization for MYC as well as both BCL2 and BCL6 rearrangements. Cohorts were defined by the presence (+) or absence (-) of rearrangements: MYC+/BCL2+/BCL6- (BCL2-DHL), MYC+/BCL2-/BCL6+ (BCL6-DHL), and MYC+/BCL2+/BCL6+ (triple-hit lymphoma; THL). RESULTS: A total of 117 patients were included in the current analysis (76 BCL2-DHLpatients, 16 BCL6-DHLpatients, and 25 THLpatients). Compared with patients with BCL2-DHL, those with BCL6-DHL were more likely to be classified as having a non-germinal center cell of origin, presented with extranodal disease, and appeared to achieve higher rates of complete response despite receiving intensive induction therapy less frequently. However, patients with BCL6-DHL experienced a shorter median overall survival if achieving an initial complete response compared with patients with BCL2-DHL. Patients with THL experienced survival outcomes similar to those of patients with BCL2-DHL. CONCLUSIONS: Recognition of the specific oncogene rearrangements may be of prognostic value and potentially guide future therapeutic strategies for patients with DHL.
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