title: Impact of oncogene rearrangement patterns on outcomes in patients with double-hit non-Hodgkin lymphoma.
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.
authors.affiliation: Division of Hematology/Oncology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Landsburg
authors.affiliation: Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Petrich
authors.affiliation: Center for Lymphoma, Massachusetts General Hospital Cancer Center, Boston, Massachusetts.
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Abramson
authors.affiliation: Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Aliyah R
authors.initials: AR
authors.lastname: Sohani
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Oliver
authors.initials: O
authors.lastname: Press
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Ryan
authors.initials: R
authors.lastname: Cassaday
authors.affiliation: Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, Florida.
authors.forename: Julio C
authors.initials: JC
authors.lastname: Chavez
authors.affiliation: Leukemia/BMT Program of British Columbia, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Kevin
authors.initials: K
authors.lastname: Song
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Zelenetz
authors.affiliation: Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois.|Virginia Cancer Specialists, Fairfax, Virginia.
authors.forename: Mitul
authors.initials: M
authors.lastname: Gandhi
authors.affiliation: Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Namrata
authors.initials: N
authors.lastname: Shah
authors.affiliation: Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Fenske
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jesse
authors.initials: J
authors.lastname: Jaso
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin.
authors.forename: David T
authors.initials: DT
authors.lastname: Yang
authors.affiliation: Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, Illinois.
authors.forename: Chadi
authors.initials: C
authors.lastname: Nabhan
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019046:Bone Marrow Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002051:Burkitt Lymphoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D016543:Central Nervous System Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000627:therapeutic use; D003561:Cytarabine / Q000627:therapeutic use; D004268:DNA-Binding Proteins / Q000235:genetics*; D016208:Databases, Factual; D003907:Dexamethasone / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D015321:Gene Rearrangement; D019254:Genes, bcl-2 / Q000235:genetics*; D016259:Genes, myc / Q000235:genetics*; D018858:Germinal Center / Q000473:pathology*; D006801:Humans; D007069:Ifosfamide / Q000627:therapeutic use; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D051560:Proto-Oncogene Proteins c-bcl-6; D000069283:Rituximab / Q000008:administration & dosage; D015996:Survival Rate; D014750:Vincristine / Q000627:therapeutic use
chemical_list: C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D003561:Cytarabine; D000069283:Rituximab; D014750:Vincristine; D005047:Etoposide; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D007069:Ifosfamide; D011241:Prednisone; D008727:Methotrexate
keywords: BCL2 (B-cell lymphoma 2); BCL6 (B-cell lymphoma 6); MYC; gene rearrangement; non-Hodgkin lymphoma