title: A multicentre retrospective comparison of central nervous system prophylaxis strategies among patients with high-risk diffuse large B-cell lymphoma.
abstract: BACKGROUND
  Central nervous system (CNS) relapse in diffuse large B-cell lymphoma (DLBCL) is a devastating complication; the optimal prophylactic strategy remains unclear.
  
  
  METHODS
  We performed a multicentre, retrospective analysis of patients with DLBCL with high risk for CNS relapse as defined by two or more of: multiple extranodal sites, elevated serum LDH and B symptoms or involvement of specific high-risk anatomical sites. We compared three different strategies of CNS-directed therapy: intrathecal (IT) methotrexate (MTX) with (R)-CHOP 'group 1'; R-CHOP with IT MTX and two cycles of high-dose intravenous (IV) MTX 'group 2'; dose-intensive systemic antimetabolite-containing chemotherapy (Hyper-CVAD or CODOXM/IVAC) with IT/IV MTX 'group 3'.
  
  
  RESULTS
  Overall, 217 patients were identified (49, 125 and 43 in groups 1-3, respectively). With median follow-up of 3.4 (range 0.2-18.6) years, 23 CNS relapses occurred (12, 10 and 1 in groups 1-3 respectively). The 3-year actuarial rates (95% CI) of CNS relapse were 18.4% (9.5-33.1%), 6.9% (3.5-13.4%) and 2.3% (0.4-15.4%) in groups 1-3, respectively (P=0.009).
  
  
  CONCLUSIONS
  The addition of high-dose IV MTX and/or cytarabine was associated with lower incidence of CNS relapse compared with IT chemotherapy alone. However, these data are limited by their retrospective nature and warrant confirmation in prospective randomised studies.
authors: 1] Department of Haematology, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, Melbourne, Victoria 8006, Australia [2] Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia.
authors: C Y
authors: CY
authors: Cheah
authors: 1] Department of Haematology, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, Melbourne, Victoria 8006, Australia [2] Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia [3] Cabrini Medical Centre, Malvern, Victoria, Australia.
authors: K E
authors: KE
authors: Herbert
authors: Department of Haematology, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
authors: K
authors: K
authors: O'Rourke
authors: 1] Department of Haematology, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia [2] University of Queensland, St Lucia, Queensland, Australia.
authors: G A
authors: GA
authors: Kennedy
authors: Department of Haematology, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, Melbourne, Victoria 8006, Australia.
authors: A
authors: A
authors: George
authors: Department of Haematology, Monash Health, Clayton, Victoria, Australia.
authors: P L
authors: PL
authors: Fedele
authors: 1] Department of Haematology, Monash Health, Clayton, Victoria, Australia [2] Department of Haematology, Monash University, Clayton, Victoria, Australia.
authors: M
authors: M
authors: Gilbertson
authors: Department of Haematology, Monash Health, Clayton, Victoria, Australia.
authors: S Y
authors: SY
authors: Tan
authors: 1] Department of Haematology, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, Melbourne, Victoria 8006, Australia [2] Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia.
authors: D S
authors: DS
authors: Ritchie
authors: 1] Department of Haematology, Monash Health, Clayton, Victoria, Australia [2] Department of Haematology, Monash University, Clayton, Victoria, Australia.
authors: S S
authors: SS
authors: Opat
authors: 1] Department of Haematology, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, Melbourne, Victoria 8006, Australia [2] Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia [3] Cabrini Medical Centre, Malvern, Victoria, Australia [4] Department of Haematology, Monash University, Clayton, Victoria, Australia.
authors: H M
authors: HM
authors: Prince
authors: 1] Department of Haematology, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, Melbourne, Victoria 8006, Australia [2] Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia.
authors: M
authors: M
authors: Dickinson
authors: 1] Department of Haematology, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, Melbourne, Victoria 8006, Australia [2] Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia.
authors: K
authors: K
authors: Burbury
authors: 1] Department of Haematology, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, Melbourne, Victoria 8006, Australia [2] Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia [3] Cabrini Medical Centre, Malvern, Victoria, Australia.
authors: M
authors: M
authors: Wolf
authors: Department of Haematology, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, Melbourne, Victoria 8006, Australia.
authors: E H
authors: EH
authors: Januszewicz
authors: 1] Department of Haematology, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, Melbourne, Victoria 8006, Australia [2] Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia.
authors: C S
authors: CS
authors: Tam
authors: 1] Department of Haematology, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, Melbourne, Victoria 8006, Australia [2] Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia.
authors: D A
authors: DA
authors: Westerman
authors: 1] Department of Haematology, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, Melbourne, Victoria 8006, Australia [2] Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia.
authors: D A
authors: DA
authors: Carney
authors: 1] Department of Haematology, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, Melbourne, Victoria 8006, Australia [2] Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia.
authors: S J
authors: SJ
authors: Harrison
authors: 1] Department of Haematology, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, Melbourne, Victoria 8006, Australia [2] Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia.
authors: J F
authors: JF
authors: Seymour
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced; D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000517:prevention & control* / Q000556:secondary; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007278:Injections, Spinal; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D012008:Recurrence; D012189:Retrospective Studies; D018570:Risk Assessment; D000069283:Rituximab; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; C571759:R-CHOP protocol; D003561:Cytarabine; D000069283:Rituximab; D014750:Vincristine; D005047:Etoposide; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D007069:Ifosfamide; D011241:Prednisone; D008727:Methotrexate