title: High-dose chemotherapy with autologous haemopoietic stem cell transplantation for newly diagnosed primary CNS lymphoma: a prospective, single-arm, phase 2 trial.
abstract: BACKGROUND
  High-dose methotrexate-based chemotherapy is standard for primary CNS lymphoma, but most patients relapse. High-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) is supposed to overcome the blood-brain barrier and eliminate residual disease in the CNS. We aimed to investigate the safety and efficacy of HCT-ASCT in patients with newly diagnosed primary CNS lymphoma.
  
  
  METHODS
  In this prospective, single-arm, phase 2 trial, we recruited patients aged 18-65 years with newly diagnosed primary CNS lymphoma and immunocompetence, with no limitation on clinical performance status, from 15 hospitals in Germany. Patients received five courses of intravenous rituximab 375 mg/m(2) (7 days before first high-dose methotrexate course and then every 10 days) and four courses of intravenous high-dose methotrexate 8000 mg/m(2) (every 10 days) and then two courses of intravenous rituximab 375 mg/m(2) (day 1), cytarabine 3 g/m(2) (days 2 and 3), and thiotepa 40 mg/m(2) (day 3). 3 weeks after the last course, patients commenced intravenous HCT-ASCT (rituximab 375 mg/m(2) [day 1], carmustine 400 mg/m(2) [day 2], thiotepa 2 × 5 mg/kg [days 3 and 4], and infusion of stem cells [day 7]), irrespective of response status after induction. We restricted radiotherapy to patients without complete response after HCT-ASCT. The primary endpoint was complete response at day 30 after HCT-ASCT in all registered eligible patients who received at least 1 day of study treatment. This trial is registered at ClinicalTrials.gov, number NCT00647049.
  
  
  RESULTS
  Between Jan 18, 2007, and May 23, 2011, we recruited 81 patients, of whom two (2%) were excluded, therefore we included 79 (98%) patients in the analysis. All patients started induction treatment; 73 (92%) commenced HCT-ASCT. 61 (77·2% [95% CI 66·1-86·6]) patients achieved a complete response. During induction treatment, the most common grade 3 toxicity was anaemia (37 [47%]) and the most common grade 4 toxicity was thrombocytopenia (50 [63%]). During HCT-ASCT, the most common grade 3 toxicity was fever (50 [68%] of 73) and the most common grade 4 toxicity was leucopenia (68 [93%] of 73). We recorded four (5%) treatment-related deaths (three [4%] during induction and one [1%] 4 weeks after HCT-ASCT).
  
  
  CONCLUSIONS
  HCT-ASCT with thiotepa and carmustine is an effective treatment option in young patients with newly diagnosed primary CNS lymphoma, but further comparative studies are needed.
  
  
  BACKGROUND
  University Hospital Freiburg and Amgen.
authors.affiliation: Department of Haematology/Oncology and Palliative Care, Klinikum Stuttgart, Stuttgart, Germany; Department of Hematology, Oncology, and Stem-Cell Transplantation, University Medical Hospital and Faculty of Medicine, Albert-Ludwigs University, Freiburg, Germany. Electronic address: g.illerhaus@klinikum-stuttgart.de.
authors.forename: Gerald
authors.initials: G
authors.lastname: Illerhaus
authors.affiliation: Department of Haematology/Oncology and Palliative Care, Klinikum Stuttgart, Stuttgart, Germany; Department of Medicine, Royal Marsden Hospital, London, UK.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kasenda
authors.affiliation: Clinical Trials Unit, University of Freiburg Medical Centre, Freiburg, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Ihorst
authors.affiliation: Department of Haematology and Oncology, Heidelberg University, Heidelberg, Germany.
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Egerer
authors.affiliation: Department of Internal Medicine II, University Hospital of Schleswig-Holstein, Kiel, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Lamprecht
authors.affiliation: III Medical Department, Technische Universität München, Munich, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keller
authors.affiliation: Department of Haematology and Oncology, University Hospital Halle, Halle, Germany.
authors.forename: Hans-Heinrich
authors.initials: HH
authors.lastname: Wolf
authors.affiliation: Hematology and Oncology, Clinic for Internal Medicine C, University of Greifswald, Greifswald, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Hirt
authors.affiliation: Department of Internal Medicine III, University of Ulm, Ulm, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Stilgenbauer
authors.affiliation: Department of Internal Medicine II, Oncology, Hematology, and Bone Marrow Transplantation with section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Mascha
authors.initials: M
authors.lastname: Binder
authors.affiliation: Department of Neurology and Wilhelm Sander-NeuroOncology Unit, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hau
authors.affiliation: Department of Medicine, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Edinger
authors.affiliation: Department of Haematology and Oncology, HELIOS Dr Horst Schmidt Kliniken, Wiesbaden, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Frickhofen
authors.affiliation: Medizinische Klinik, Städtisches Klinikum Karlsruhe, Karlsruhe, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Bentz
authors.affiliation: Department of Haematology and Oncology, University of Tübingen, Tübingen, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Möhle
authors.affiliation: Department of Haematology, Medical Faculty, University of Duisburg-Essen, Essen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Röth
authors.affiliation: Klinik für Innere Medizin I, Universität des Saarlandes, Homburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Pfreundschuh
authors.affiliation: Department of Neurology, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Louisa
authors.initials: L
authors.lastname: von Baumgarten
authors.affiliation: Institute of Neuropathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Deckert
authors.affiliation: Department of Neuroradiology, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Hader
authors.affiliation: Department of Hematology, Oncology, and Stem-Cell Transplantation, University Medical Hospital and Faculty of Medicine, Albert-Ludwigs University, Freiburg, Germany.
authors.forename: Heidi
authors.initials: H
authors.lastname: Fricker
authors.affiliation: Department of Haematology/Oncology and Palliative Care, Klinikum Stuttgart, Stuttgart, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Valk
authors.affiliation: Department of Hematology, Oncology, and Stem-Cell Transplantation, University Medical Hospital and Faculty of Medicine, Albert-Ludwigs University, Freiburg, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Schorb
authors.affiliation: Department of Hematology, Oncology, and Stem-Cell Transplantation, University Medical Hospital and Faculty of Medicine, Albert-Ludwigs University, Freiburg, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Fritsch
authors.affiliation: Department of Hematology, Oncology, and Stem-Cell Transplantation, University Medical Hospital and Faculty of Medicine, Albert-Ludwigs University, Freiburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Finke
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002330:Carmustine / Q000008:administration & dosage; D016543:Central Nervous System Neoplasms / Q000175:diagnosis / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis / Q000628:therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D000069283:Rituximab / Q000008:administration & dosage; D015996:Survival Rate; D013852:Thiotepa / Q000008:administration & dosage; D014182:Transplantation, Autologous; D055815:Young Adult
chemical_list: D000069283:Rituximab; D013852:Thiotepa; D002330:Carmustine; D008727:Methotrexate