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Title: 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.
Austin Authors: Wight, Joel C ;Yue, Mimi;Keane, Colm;Johnston, Anna;Linton, Kim;Chin, Collin;Wai, Shin Hnin;Talaulikar, Dipti;Gasiorowski, Robin;Cheah, Chan Yoon;Gregory, Gareth P;Dickinson, Michael;Minson, Adrian;Coombes, Caitlin;Ku, Matthew;Lam, Stephanie;Hawkes, Eliza A 
Affiliation: University of Queensland, Brisbane, Queensland, Australia
The Christie NHS Foundation Trust, Manchester, UK
University of Western Australia Medical School, Melbourne, Victoria, Australia
The Manchester Cancer Research Centre, Manchester, UK
Royal Hobart Hospital, Hobart, Australia
Concord Hospital, Sydney, New South Wales, Australia
University of Sydney, Sydney, New South Wales, Australia
Australian National University Medical School, Canberra, Australian Capital Territory, Australia
Princess Alexandra Hospital, Brisbane, Queensland, Australia
Monash Health, Clayton, Victoria, Australia
School of Clinical Sciences at Monash Health, Monash University, Melbourne, Victoria, Australia
Austin Health, Heidelberg, Victoria, Australia
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
The University of Melbourne, Melbourne, Victoria, Australia
La Trobe University, Melbourne, Victoria, Australia
Royal Perth Hospital, Perth, Western Australia, Australia
St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
Canberra Hospital, Canberra, Australian Capital Territory, Australia
Clinical Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Victoria, Australia
The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia
Sir Charles Gardiner Hospital, Perth, Western Australia, Australia
Issue Date: 2019
Date: 2019-06-24
Publication information: British journal of haematology 2019; 187(2): 174-184
Abstract: 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.
DOI: 10.1111/bjh.16064
ORCID: 0000-0002-3216-2392
Journal: British journal of haematology
PubMed URL: 31236941
Type: Journal Article
Subjects: central nervous system lymphoma
de novo diffuse large B-cell lymphoma
synchronous lymphoma
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