Outcomes of synchronous systemic and central nervous system (CNS) involvement of diffuse large B-cell lymphoma are dictated by the CNS disease: a collaborative study of the Australasian Lymphoma Alliance

Joel C. Wight, Mimi Yue, Colm Keane, Anna Johnston, Kim Linton, Collin Chin, Shin Hnin Wai, Dipti Talaulikar, Robin Gasiorowski, Chan Yoon Cheah, Gareth P. Gregory, Michael Dickinson, Adrian Minson, Caitlin Coombes, Matthew Ku, Stephanie Lam, Eliza A. Hawkes

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23 Citations (Scopus)


De novo diffuse large B-cell lymphoma (DLBCL) presenting with synchronous central nervous system (CNS) and systemic disease (synDLBCL) is not well described and is excluded from clinical trials. We performed a retrospective analysis of 80 synDLBCL patients treated across 10 Australian and UK centres. Of these patients, 96% had extranodal systemic disease. CNS-directed treatment with combination intravenous cytarabine and high-dose methotrexate (“CNS-intensive”) (n = 38) was associated with favourable survival outcomes compared with “CNS-conservative” strategies such as intravenous high-dose methotrexate monotherapy, intrathecal therapy and/or radiotherapy (2-year progression-free survival [PFS] 50% vs. 31%, P = 0·006; 2-year overall survival [OS] 54% vs. 44%, P = 0·037). Outcomes were primarily dictated by the ability to control the CNS disease, with 2-year cumulative CNS relapse incidence of 42% and non-CNS relapse 21%. Two-year OS for CNS-relapse patients was 13% vs. 36% for non-CNS relapses (P = 0·02). Autologous stem cell transplantation as consolidation (n = 14) was not observed to improve survival in those patients who received CNS-intensive induction when matched for induction outcomes (2-year PFS 69% vs. 56%, P = 0·99; 2-year OS 66% vs. 56%, P = 0·98). Hyperfractionated or infusional systemic treatment did not improve survival compared to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) (2-year OS 49% for both groups). Our study suggests that adequate control of the CNS disease is paramount and is best achieved by intensive CNS-directed induction.

Original languageEnglish
Pages (from-to)174-184
Number of pages11
JournalBritish Journal of Haematology
Issue number2
Publication statusPublished - 1 Jan 2019


  • central nervous system lymphoma
  • cytarabine
  • de novo diffuse large B-cell lymphoma
  • synchronous lymphoma

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