title: Treatment of secondary central nervous system lymphoma with intrathecal rituximab, high-dose methotrexate, and R-DHAP followed by autologous stem cell transplantation: results of the HOVON 80 phase 2 study.
abstract: The prognosis of central nervous system (CNS) relapse of systemic non-Hodgkin lymphoma is poor with 1-year survival historically at 0% to 20%. Aiming to improve these results, we performed a multicenter phase 2 study in patients with a CNS relapse, with or without concurrent systemic relapse. Treatment consisted of 2 cycles of R-DHAP alternating with high-dose methotrexate (MTX) and was combined with intrathecal rituximab. Responding patients received a third R-DHAP-MTX cycle followed by busulfan and cyclophosphamide myeloablative therapy and autologous stem cell transplantation. In patients with persistent cerebrospinal fluid lymphoma after cycle 1, the intrathecal rituximab was replaced by intrathecal triple therapy, with MTX, cytarabine, and dexamethasone. Thirty-six patients were included. Eighteen had evidence of cerebrospinal fluid lymphoma, 24 had brain parenchymal disease, and 20 (56%) had concurrent systemic disease. The overall response rate after 2 R-DHAP-MTX was 53% (19/36), with 22% (8/36) complete remission. Fifteen patients (42%) underwent a transplant. One-year progression-free survival was 19% (95% confidence interval, 9-34): 25% in patients without and 15% in patients with systemic disease. One-year overall survival was 25% (95% confidence interval, 12-40). This treatment regimen did not result in a major improvement of outcome of secondary CNS lymphoma, especially when concurrent systemic disease was present. Registered in the Dutch trial register www.trialregister.nl, NTR1757; EudraCT number 2006-002141-37.
authors.affiliation: Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Jeanette K
authors.initials: JK
authors.lastname: Doorduijn
authors.affiliation: Department of Hematology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Gustaaf W
authors.initials: GW
authors.lastname: van Imhoff
authors.affiliation: HOVON Data Center, Erasmus MC Cancer Institute-Clinical Trial Center, Rotterdam, The Netherlands.
authors.forename: Bronno
authors.initials: B
authors.lastname: van der Holt
authors.affiliation: Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Harry C
authors.initials: HC
authors.lastname: Schouten
authors.affiliation: Department of Internal Medicine, Medisch Spectrum Twente, Enschede, The Netherlands.
authors.forename: Martijn R
authors.initials: MR
authors.lastname: Schaafsma
authors.affiliation: Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Marius A
authors.initials: MA
authors.lastname: MacKenzie
authors.affiliation: Department of Medical Oncology, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: Joke W
authors.initials: JW
authors.lastname: Baars
authors.affiliation: Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Marie José
authors.initials: MJ
authors.lastname: Kersten
authors.affiliation: Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Pieternella J
authors.initials: PJ
authors.lastname: Lugtenburg
authors.affiliation: Department of Neuro-oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: van den Bent
authors.affiliation: Department of Neurology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Roelien H
authors.initials: RH
authors.lastname: Enting
authors.affiliation: HOVON Data Center, Erasmus MC Cancer Institute-Clinical Trial Center, Rotterdam, The Netherlands.
authors.forename: Fokje M
authors.initials: FM
authors.lastname: Spoelstra
authors.affiliation: Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Philip
authors.initials: P
authors.lastname: Poortmans
authors.affiliation: Department of Neuro-oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Jacoline E C
authors.initials: JEC
authors.lastname: Bromberg
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000627:therapeutic use; D003561:Cytarabine / Q000627:therapeutic use; D003907:Dexamethasone / Q000627:therapeutic use; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D011379:Prognosis; D000069283:Rituximab / Q000627:therapeutic use*; D014182:Transplantation, Autologous / Q000379:methods*; D055815:Young Adult
chemical_list: D003561:Cytarabine; D000069283:Rituximab; D003907:Dexamethasone; D002945:Cisplatin; D008727:Methotrexate
keywords: clinical trial; methotrexate; rituximab; secondary CNS lymphoma; transplantation; treatment