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Title: Central nervous system relapse of diffuse large B-cell lymphoma in the rituximab era: results of the UK NCRI R-CHOP-14 versus 21 trial.
Austin Authors: Gleeson, M;Counsell, Nicholas;Cunningham, D;Chadwick, N;Lawrie, A;Hawkes, Eliza A ;McMillan, A;Ardeshna, K M;Jack, A;Smith, P;Mouncey, P;Pocock, C;Radford, J A;Davies, J;Turner, D;Kruger, A;Johnson, P ;Gambell, J;Linch, D
Affiliation: Department of Medicine, The Royal Marsden Hospital, London and Surrey, UK
Cancer Research UK and UCL Cancer Trials Centre, UCL Cancer Institute, London, UK
Department of Oncology and Clinical Haematology, Austin Health, Heidelberg, Melbourne, Australia
Department of Medical Oncology, Eastern Health, Melbourne, Australia
Department of Haematology, Nottingham City Hospital, Nottingham, UK
Department of Haematology, University College London, London, UK
Department of Haematology, Mount Vernon Cancer Centre, Northwood, UK
HMDS, Leeds Teaching Hospitals NHS Trust, Leeds, UK
Department of Haematology, East Kent Hospitals, Canterbury, UK
The University of Manchester and The Christie NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
Department of Haematology, Western General Hospital, Edinburgh, UK
Department of Haematology, Torbay Hospital, Torquay, UK
Department of Haematology, Royal Cornwall Hospital, Truro, UK
Cancer Research UK Centre, Southampton, UK
Issue Date: 1-Oct-2017
Publication information: Annals of oncology 2017; 28(10): 2511-2516
Abstract: Central nervous system (CNS) relapse of diffuse large B-cell lymphoma (DLBCL) is associated with a dismal prognosis. Here, we report an analysis of CNS relapse for patients treated within the UK NCRI phase III R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) 14 versus 21 randomised trial. The R-CHOP 14 versus 21 trial compared R-CHOP administered two- versus three weekly in previously untreated patients aged ≥18 years with bulky stage I-IV DLBCL (n = 1080). Details of CNS prophylaxis were retrospectively collected from participating sites. The incidence and risk factors for CNS relapse including application of the CNS-IPI were evaluated. 177/984 patients (18.0%) received prophylaxis (intrathecal (IT) methotrexate (MTX) n = 163, intravenous (IV) MTX n = 2, prophylaxis type unknown n = 11 and IT MTX and cytarabine n = 1). At a median follow-up of 6.5 years, 21 cases of CNS relapse (isolated n = 11, with systemic relapse n = 10) were observed, with a cumulative incidence of 1.9%. For patients selected to receive prophylaxis, the incidence was 2.8%. Relapses predominantly involved the brain parenchyma (81.0%) and isolated leptomeningeal involvement was rare (14.3%). Univariable analysis demonstrated the following risk factors for CNS relapse: performance status 2, elevated lactate dehydrogenase, IPI, >1 extranodal site of disease and presence of a 'high-risk' extranodal site. Due to the low number of events no factor remained significant in multivariate analysis. Application of the CNS-IPI revealed a high-risk group (4-6 risk factors) with a 2- and 5-year incidence of CNS relapse of 5.2% and 6.8%, respectively. Despite very limited use of IV MTX as prophylaxis, the incidence of CNS relapse following R-CHOP was very low (1.9%) confirming the reduced incidence in the rituximab era. The CNS-IPI identified patients at highest risk for CNS recurrence. ISCRTN number 16017947 (R-CHOP14v21); EudraCT number 2004-002197-34.
DOI: 10.1093/annonc/mdx353
Journal: Annals of oncology : official journal of the European Society for Medical Oncology
PubMed URL: 28961838
Type: Journal Article
Subjects: central nervous system
diffuse large B-cell lymphoma
Appears in Collections:Journal articles

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