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

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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. Patients and 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. NCT01502982.


  • H. Holte
  • S. Leppa
  • M. Bjorkholm
  • O. Fluge
  • S. Jyrkkio
  • J. Delabie
  • C. Sundstrom
  • M. -L. Karjalainen-Lindsberg
  • M. Erlanson
  • A. Kolstad
  • A. Fossa
  • B. Ostenstad
  • E. Lofvenberg
  • M. Nordstrom
  • R. Janes
  • L. M. Pedersen
  • Harald Anderson
  • Mats Jerkeman
  • Mikael Eriksson
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology


  • age-adjusted IPI, central nervous system, diffuse large B-cell lymphoma, intensive chemotherapy, prophylaxis
Original languageEnglish
Pages (from-to)1385-1392
JournalAnnals of Oncology
Issue number5
Publication statusPublished - 2013
Publication categoryResearch

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