title: Dose-densified chemoimmunotherapy followed by systemic central nervous system prophylaxis for younger high-risk diffuse large B-cell/follicular grade 3 lymphoma patients: results of a phase II Nordic Lymphoma Group study.
abstract: BACKGROUND
  Many patients with aggressive B-cell lymphomas and high clinical risk score still die of lymphoma after conventional R-CHOP chemoimmunotherapy. We hypothesized that intensified chemoimmunotherapy including systemic central nervous system (CNS) prophylaxis improves outcome and reduces the incidence of CNS-related events.
  
  
  METHODS
  Inclusion criteria were age 18-65 years, primary diffuse large B-cell lymphoma or grade III follicular lymphoma without clinical signs of CNS disease and negative cerebrospinal fluid cytology, age-adjusted International Prognostic Index 2-3 and WHO performance score 0-3. Treatment consisted of six courses of R-CHOEP-14 followed by a course of high-dose cytarabine and a course of high-dose methotrexate. Primary end point was failure-free survival (FFS) at 3 years.
  
  
  RESULTS
  A total of 156 eligible patients with a median age of 54 years (range 20-64) were included. Three toxic deaths were observed. Three-year overall survival (OS) and FFS rates (median observation time 52 months for survivors) were 81% and 65%, respectively. Seven patients experienced CNS relapse, all within 6 months.
  
  
  CONCLUSIONS
  The results are promising with favorable 3-year OS and FFS rates, a low toxic death rate and a lower than expected number of CNS events. CNS progression might be further reduced by earlier CNS prophylaxis. CinicalTrials.gov. identifier NCT01502982.
authors.affiliation: Department of Oncology, Oslo University Hospital, Oslo, Norway. hhe@ous-hf.no
authors.forename: H
authors.initials: H
authors.lastname: Holte
authors.forename: S
authors.initials: S
authors.lastname: Leppä
authors.forename: M
authors.initials: M
authors.lastname: Björkholm
authors.forename: O
authors.initials: O
authors.lastname: Fluge
authors.forename: S
authors.initials: S
authors.lastname: Jyrkkiö
authors.forename: J
authors.initials: J
authors.lastname: Delabie
authors.forename: C
authors.initials: C
authors.lastname: Sundström
authors.forename: M-L
authors.initials: ML
authors.lastname: Karjalainen-Lindsberg
authors.forename: M
authors.initials: M
authors.lastname: Erlanson
authors.forename: A
authors.initials: A
authors.lastname: Kolstad
authors.forename: A
authors.initials: A
authors.lastname: Fosså
authors.forename: B
authors.initials: B
authors.lastname: Ostenstad
authors.forename: E
authors.initials: E
authors.lastname: Löfvenberg
authors.forename: M
authors.initials: M
authors.lastname: Nordström
authors.forename: R
authors.initials: R
authors.lastname: Janes
authors.forename: L M
authors.initials: LM
authors.lastname: Pedersen
authors.forename: H
authors.initials: H
authors.lastname: Anderson
authors.forename: M
authors.initials: M
authors.lastname: Jerkeman
authors.forename: M
authors.initials: M
authors.lastname: Eriksson
mesh_terms: D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002490:Central Nervous System / Q000187:drug effects*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy / Q000517:prevention & control*; D003520:Cyclophosphamide / Q000627:therapeutic use; D003561:Cytarabine / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007167:Immunotherapy; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D011241:Prednisone / Q000627:therapeutic use; D000069283:Rituximab; D014750:Vincristine / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; C571759:R-CHOP protocol; D003561:Cytarabine; D000069283:Rituximab; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone