title: Targeting intratumoral B cells with rituximab in addition to CHOP in angioimmunoblastic T-cell lymphoma. A clinicobiological study of the GELA.
abstract: BACKGROUND
  In angioimmunoblastic T-cell lymphoma, symptoms linked to B-lymphocyte activation are common, and variable numbers of CD20(+) large B-blasts, often infected by Epstein-Barr virus, are found in tumor tissues. We postulated that the disruption of putative B-T interactions and/or depletion of the Epstein-Barr virus reservoir by an anti-CD20 monoclonal antibody (rituximab) could improve the clinical outcome produced by conventional chemotherapy.
  
  
  METHODS
  Twenty-five newly diagnosed patients were treated, in a phase II study, with eight cycles of rituximab + chemotherapy (R-CHOP21). Tumor infiltration, B-blasts and Epstein-Barr virus status in tumor tissue and peripheral blood were fully characterized at diagnosis and were correlated with clinical outcome.
  
  
  RESULTS
  A complete response rate of 44% (95% CI, 24% to 65%) was observed. With a median follow-up of 24 months, the 2-year progression-free survival rate was 42% (95% CI, 22% to 61%) and overall survival rate was 62% (95% CI, 40% to 78%). The presence of Epstein-Barr virus DNA in peripheral blood mononuclear cells (14/21 patients) correlated with Epstein-Barr virus score in lymph nodes (P<0.004) and the detection of circulating tumor cells (P=0.0019). Despite peripheral Epstein-Barr virus clearance after treatment, the viral load at diagnosis (>100 copy/μg DNA) was associated with shorter progression-free survival (P=0.06).
  
  
  CONCLUSIONS
  We report here the results of the first clinical trial targeting both the neoplastic T cells and the microenvironment-associated CD20(+) B lymphocytes in angioimmunoblastic T-cell lymphoma, showing no clear benefit of adding rituximab to conventional chemotherapy. A strong relationship, not previously described, between circulating Epstein-Barr virus and circulating tumor cells is highlighted.
authors.affiliation: Faculté de Médecine, Université Paris Est Creteil, UPEC, Créteil, France. delfau@hmn.aphp.fr
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Delfau-Larue
authors.forename: Laurence
authors.initials: L
authors.lastname: de Leval
authors.forename: Bertrand
authors.initials: B
authors.lastname: Joly
authors.forename: Anne
authors.initials: A
authors.lastname: Plonquet
authors.forename: Dominique
authors.initials: D
authors.lastname: Challine
authors.forename: Marie
authors.initials: M
authors.lastname: Parrens
authors.forename: Alain
authors.initials: A
authors.lastname: Delmer
authors.forename: Gilles
authors.initials: G
authors.lastname: Salles
authors.forename: Franck
authors.initials: F
authors.lastname: Morschhauser
authors.forename: Richard
authors.initials: R
authors.lastname: Delarue
authors.forename: Pauline
authors.initials: P
authors.lastname: Brice
authors.forename: Reda
authors.initials: R
authors.lastname: Bouabdallah
authors.forename: Olivier
authors.initials: O
authors.lastname: Casasnovas
authors.forename: Hervé
authors.initials: H
authors.lastname: Tilly
authors.forename: Philippe
authors.initials: P
authors.lastname: Gaulard
authors.forename: Corinne
authors.initials: C
authors.lastname: Haioun
mesh_terms: D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000473:pathology / Q000821:virology; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007119:Immunoblastic Lymphadenopathy / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016399:Lymphoma, T-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D000069283:Rituximab; D016896:Treatment Outcome; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone