title: Phase 2 trial of high-dose rituximab with high-dose cytarabine mobilization therapy and high-dose thiotepa, busulfan, and cyclophosphamide autologous stem cell transplantation in patients with central nervous system involvement by non-Hodgkin lymphoma.
abstract: BACKGROUND
  High-dose thiotepa, busulfan, and cyclophosphamide (TBC) with autologous stem cell transplantation (ASCT) has been used in patients with central nervous system (CNS) involvement by non-Hodgkin lymphoma (NHL). Despite limited penetration into the CNS, rituximab is active in primary CNS NHL. Therefore, high-dose rituximab was combined with TBC for ASCT in patients with CNS NHL.
  
  
  METHODS
  A single-arm phase 2 trial using high-dose rituximab with cytarabine for stem cell mobilization followed by high-dose rituximab combined with thiotepa, busulfan, and cyclophosphamide (R-TBC) for ASCT was conducted. Doses of rituximab at 1000 mg/m(2) were given on days 1 and 8 of mobilization and on days -9 and -2 of TBC. The primary endpoint was efficacy.
  
  
  RESULTS
  Thirty patients were enrolled. Eighteen patients had primary CNS NHL (12 with complete remission (CR)/first partial remission (PR1) and 6 with CR/PR2), and 12 patients had secondary CNS lymphoma (5 with CR/PR1 and 7 with CR/PR2 or beyond). All patients were in partial or complete remission. Twenty-nine patients proceeded to R-TBC ASCT. Two patients developed significant neurotoxicity. The 100-day nonrelapse mortality rate was 0%, and 1 patient died because of nonrelapse causes 5 months after ASCT. For all patients, at a median follow-up of 24 months (range, 12-40 months), the estimated 2-year progression-free survival rate was 81% (95% confidence interval, 59%-92%), and the 2-year overall survival rate was 93% (95% confidence interval, 76%-98%). There were no relapses or deaths among the 18 patients with primary CNS lymphoma.
  
  
  CONCLUSIONS
  For patients with CNS involvement by B-cell NHL and especially for patients with primary CNS NHL, R-TBC ASCT shows encouraging activity and merits further study.
authors.affiliation: Bone Marrow Transplant Unit, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Yi-Bin
authors.initials: YB
authors.lastname: Chen
authors.forename: Tracy
authors.initials: T
authors.lastname: Batchelor
authors.forename: Shuli
authors.initials: S
authors.lastname: Li
authors.forename: Ephraim
authors.initials: E
authors.lastname: Hochberg
authors.forename: Mark
authors.initials: M
authors.lastname: Brezina
authors.forename: Sooae
authors.initials: S
authors.lastname: Jones
authors.forename: Candice
authors.initials: C
authors.lastname: Del Rio
authors.forename: Morgan
authors.initials: M
authors.lastname: Curtis
authors.forename: Karen K
authors.initials: KK
authors.lastname: Ballen
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Barnes
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Chi
authors.forename: Jorg
authors.initials: J
authors.lastname: Dietrich
authors.forename: Jessica
authors.initials: J
authors.lastname: Driscoll
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Gertsner
authors.forename: Fred
authors.initials: F
authors.lastname: Hochberg
authors.forename: Ann S
authors.initials: AS
authors.lastname: LaCasce
authors.forename: Steven L
authors.initials: SL
authors.lastname: McAfee
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Spitzer
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Nayak
authors.forename: Philippe
authors.initials: P
authors.lastname: Armand
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage; D016543:Central Nervous System Neoplasms / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods*; D007262:Infusions, Intravenous; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D008297:Male; D008404:Massachusetts; D008875:Middle Aged; D000069283:Rituximab; D013852:Thiotepa / Q000008:administration & dosage; D019172:Transplantation Conditioning / Q000379:methods*; D014182:Transplantation, Autologous
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D003561:Cytarabine; D000069283:Rituximab; D003520:Cyclophosphamide; D013852:Thiotepa; D002066:Busulfan
keywords: autologous transplant; busulfan; central nervous system (CNS) lymphoma; cyclophosphamide (TBC); rituximab; thiotepa