title: Age-related EBV-associated B-cell lymphoproliferative disorders constitute a distinct clinicopathologic group: a study of 96 patients.
abstract: OBJECTIVE
  We have recently reported EBV+ B-cell lymphoproliferative disorders (LPD) occurring predominantly in elderly patients, which shared features of EBV+ B-cell neoplasms arising in the immunologically deteriorated patients despite no predisposing immunodeficiency and were named as senile or age-related EBV+ B-cell LPDs. To further characterize this disease, age-related EBV+ B-cell LPDs were compared with EBV-negative diffuse large B-cell lymphomas (DLBCL).
  
  
  METHODS
  Among 1,792 large B-cell LPD cases, 96 EBV+ cases with available clinical data set were enrolled for the present study. For the control group, 107 patients aged over 40 years with EBV-negative DLBCL were selected. We compared clinicopathologic data between two groups and determined prognostic factors by univariate and multivariate analysis.
  
  
  RESULTS
  Patients with age-related EBV+ B-cell LPDs showed a higher age distribution and aggressive clinical features or parameters than EBV-negative DLBCLs: 44% with performance status >1, 58% with serum lactate dehydrogenase level higher than normal, 49% with B symptoms, and higher involvement of skin and lung. Overall survival was thus significantly inferior in age-related EBV+ group than in DLBCLs. Univariate and multivariate analyses further identified two factors, B symptoms and age older than 70 years, independently predictive for survival. A prognostic model using these two variables well defined three risk groups: low risk (no adverse factors), intermediate risk (one factor), and high risk (two factors).
  
  
  CONCLUSIONS
  These findings suggest that age-related EBV+ B-cell LPDs constitute a distinct group, and innovative therapeutic strategies such as EBV-targeted T-cell therapy should be developed for this uncommon disease.
authors.affiliation: Department of Clinical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Oyama
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Naoko
authors.initials: N
authors.lastname: Asano
authors.forename: Aya
authors.initials: A
authors.lastname: Oshiro
authors.forename: Ritsuro
authors.initials: R
authors.lastname: Suzuki
authors.forename: Yoshitoyo
authors.initials: Y
authors.lastname: Kagami
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morishima
authors.forename: Kengo
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Izumo
authors.forename: Shigeo
authors.initials: S
authors.lastname: Mori
authors.forename: Koichi
authors.initials: K
authors.lastname: Ohshima
authors.forename: Junji
authors.initials: J
authors.lastname: Suzumiya
authors.forename: Naoya
authors.initials: N
authors.lastname: Nakamura
authors.forename: Masafumi
authors.initials: M
authors.lastname: Abe
authors.forename: Koichi
authors.initials: K
authors.lastname: Ichimura
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Sato
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yoshino
authors.forename: Tomoki
authors.initials: T
authors.lastname: Naoe
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Shimoyama
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kamiya
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Shigeo
authors.initials: S
authors.lastname: Nakamura
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006689:Hodgkin Disease / Q000473:pathology; D006801:Humans; D016130:Immunophenotyping; D016393:Lymphoma, B-Cell / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000188:drug therapy / Q000401:mortality / Q000473:pathology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D012189:Retrospective Studies