title: Treatment of diffuse large B-cell lymphoma with secondary central nervous system involvement: encouraging efficacy using CNS-penetrating R-IDARAM chemotherapy.
abstract: Diffuse large B-cell lymphoma with secondary involvement of the central nervous system (SCNS-DLBCL) is a rare condition carrying a poor prognosis. No optimal therapeutic regimen has been identified. We retrospectively analysed 23 patients with SCNS-DLBCL treated with R-IDARAM (rituximab 375 mg/m(2) IV day 1; methotrexate 12·5 mg by intrathecal injection day 1; idarubicin 10 mg/m(2) /day IV days 1 and 2; dexamethasone 100 mg/day IV infusion over 12 h days 1-3; cytosine arabinoside 1000 mg/m(2) /day IV over 1 h days 1 and 2; and methotrexate 2000 mg/m(2) IV over 2 h day 3. Ten out of 23 (44%) patients had CNS involvement at initial presentation ('new disease'), 10/23 (44%) had relapsed disease and 3/23 (13%) had primary refractory disease. 14/23 (61%) of patients responded - 6 (26%) complete response, 8 (35%) partial response. Grade 3-4 haematological toxicity was seen in all cycles, with no grade 3-4 or long-term neurological toxicity. Median follow-up for surviving patients was 49 months. At 2 years, estimated progression-free survival (PFS) was 39% and overall survival (OS) was 52%. Encouraging outcomes were reported in patients with new disease, with 5-year estimated PFS of 50% and OS 75%. R-IDARAM is a well-tolerated regimen with encouraging efficacy in patients with SCNS-DLBCL, although patients with relapsed or refractory disease continue to fare poorly.
authors.affiliation: Cancer Institute, Department of Haematology, University College London, London, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Maciocia
authors.affiliation: Department of Haematology, Royal London Hospital, London, UK.
authors.forename: Mohsin
authors.initials: M
authors.lastname: Badat
authors.affiliation: Department of Pharmacy, University College London Hospital, London, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Cheesman
authors.affiliation: Department of Haematology, University College London Hospital, London, UK.
authors.forename: Shirley
authors.initials: S
authors.lastname: D'Sa
authors.affiliation: Department of Haematology, University College London Hospital, London, UK.
authors.forename: Rahul
authors.initials: R
authors.lastname: Joshi
authors.affiliation: Department of Haematology, University College London Hospital, London, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Lambert
authors.affiliation: Cancer Institute, Department of Haematology, University College London, London, UK.|Department of Haematology, University College London Hospital, London, UK.
authors.forename: Sajir
authors.initials: S
authors.lastname: Mohamedbhai
authors.affiliation: Cancer Institute, Department of Haematology, University College London, London, UK.|Department of Haematology, University College London Hospital, London, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Pule
authors.affiliation: Cancer Institute, Department of Haematology, University College London, London, UK.|Department of Haematology, University College London Hospital, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Linch
authors.affiliation: Department of Haematology, University College London Hospital, London, UK.
authors.forename: Kirit
authors.initials: K
authors.lastname: Ardeshna
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy*; D003561:Cytarabine / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D007262:Infusions, Intravenous; D007278:Injections, Spinal; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D012189:Retrospective Studies; D000069283:Rituximab / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D003561:Cytarabine; D000069283:Rituximab; D003907:Dexamethasone; D008727:Methotrexate; D015255:Idarubicin
keywords: CNS relapse; central nervous system; clinical; haematological malignancy; lymphomas