title: Double-hit lymphomas constitute a highly aggressive subgroup in diffuse large B-cell lymphomas in the era of rituximab.
abstract: OBJECTIVE
  The incorporation of rituximab in immunochemotherapy has improved treatment outcomes for diffuse large B-cell lymphoma, but the prognosis for some diffuse large B-cell lymphomas remains dismal. Identification of adverse prognostic subgroups is essential for the choice of appropriate therapeutic strategy.
  
  
  METHODS
  We retrospectively investigated the impact of so-called 'double-hit' cytogenetic abnormalities, i.e. cytogenetic abnormalities involving c-MYC co-existing with other poor prognostic cytogenetic abnormalities involving BCL2, BCL6 or BACH2, on treatment outcomes for 93 consecutive diffuse large B-cell lymphoma patients.
  
  
  RESULTS
  According to the revised international prognostic index, no patients were cytogenetically diagnosed with double-hit lymphomas in the 'very good' risk group or in the 'good' risk group, while 5 of 33 patients had double-hit lymphomas in the 'poor' risk group. All the double-hit lymphoma patients possessed both nodal and extranodal involvement. The overall complete response rate was 89.3%, overall survival 87.1% and progression-free survival 75.8% over 2 years (median observation period: 644 days). The complete response rates were 93.2% for the non-double-hit lymphoma patients and 40.0% for the double-hit lymphoma patients. Significantly longer progression-free survival and overall survival were observed for the 'very good' and the 'good' risk patients than for the 'poor' risk patients. Moreover, the progression-free survival of double-hit lymphoma was significantly shorter than that of the non-double-hit lymphoma 'poor' risk patients (P = 0.016). In addition, the overall survival of the double-hit lymphoma patients also tended to be shorter than that of the non-double-hit lymphoma 'poor' risk group.
  
  
  CONCLUSIONS
  The diagnosis of double-hit lymphoma can help discriminate a subgroup of highly aggressive diffuse large B-cell lymphomas and indicate the need for the development of novel therapeutic strategies for double-hit lymphoma.
authors.affiliation: *Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, and Department of Hematology, Kyoto First Red Cross Hospital, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tsutsumi
authors.forename: Natsumi
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Hisao
authors.initials: H
authors.lastname: Nagoshi
authors.forename: Mio
authors.initials: M
authors.lastname: Yamamoto-Sugitani
authors.forename: Yuji
authors.initials: Y
authors.lastname: Shimura
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Mizutani
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nishida
authors.forename: Shigeo
authors.initials: S
authors.lastname: Horiike
authors.forename: Naoko
authors.initials: N
authors.lastname: Asano
authors.forename: Shigeo
authors.initials: S
authors.lastname: Nakamura
authors.forename: Junya
authors.initials: J
authors.lastname: Kuroda
authors.forename: Masafumi
authors.initials: M
authors.lastname: Taniwaki
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics; D002869:Chromosome Aberrations; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D051560:Proto-Oncogene Proteins c-bcl-6; D012189:Retrospective Studies; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; C491123:BACH2 protein, human; C084103:BCL6 protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D000069283:Rituximab