title: R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma.
abstract: High-dose methotrexate-based chemotherapy is the mainstay of treatment of primary central nervous system lymphoma (PCNSL), but relapses remain frequent. High-dose chemotherapy (HDC) with autologous stem-cell transplant (ASCT) may provide an alternative to address chemoresistance and overcome the blood-brain barrier. In this single-center phase-2 study, newly diagnosed PCNSL patients received 5 to 7 cycles of chemotherapy with rituximab, methotrexate (3.5 g/m(2)), procarbazine, and vincristine (R-MPV). Those with a complete or partial response proceeded with consolidation HDC with thiotepa, cyclophosphamide, and busulfan, followed by ASCT and no radiotherapy. Primary end point was 1-year progression-free survival (PFS), N = 32. Median age was 57, and median Karnofsky performance status 80. Following R-MPV, objective response rate was 97%, and 26 (81%) patients proceeded with HDC-ASCT. Among all patients, median PFS and overall survival (OS) were not reached (median follow-up: 45 months). Two-year PFS was 79% (95% confidence interval [CI], 58-90), with no events observed beyond 2 years. Two-year OS was 81% (95% CI, 63-91). In transplanted patients, 2-year PFS and OS were 81%. There were 3 treatment-related deaths. Prospective neuropsychological evaluations suggested relatively stable cognitive functions posttransplant. In conclusion, this treatment was associated with excellent disease control and survival, an acceptable toxicity profile, and no evidence of neurotoxicity thus far. This trial was registered at www.clinicaltrials.gov as NCT00596154.
authors.affiliation: Department of Neurology.
authors.forename: Antonio
authors.initials: A
authors.lastname: Omuro
authors.affiliation: Department of Neurology.
authors.forename: Denise D
authors.initials: DD
authors.lastname: Correa
authors.affiliation: Department of Neurology.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: DeAngelis
authors.affiliation: Department of Medicine, and.
authors.forename: Craig H
authors.initials: CH
authors.lastname: Moskowitz
authors.affiliation: Department of Medicine, and.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Matasar
authors.affiliation: Department of Neurology.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Kaley
authors.affiliation: Department of Neurology.
authors.forename: Igor T
authors.initials: IT
authors.lastname: Gavrilovic
authors.affiliation: Department of Neurology.
authors.forename: Craig
authors.initials: C
authors.lastname: Nolan
authors.affiliation: Department of Neurology.
authors.forename: Elena
authors.initials: E
authors.lastname: Pentsova
authors.affiliation: Department of Neurology.
authors.forename: Christian C
authors.initials: CC
authors.lastname: Grommes
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Panageas
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Raymond E
authors.initials: RE
authors.lastname: Baser
authors.affiliation: Department of Neurology.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Faivre
authors.affiliation: Department of Neurology.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Abrey
authors.affiliation: Department of Medicine, and.
authors.forename: Craig S
authors.initials: CS
authors.lastname: Sauter
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage; D016543:Central Nervous System Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011344:Procarbazine / Q000008:administration & dosage; D011379:Prognosis; D000069283:Rituximab; D015996:Survival Rate; D013852:Thiotepa / Q000008:administration & dosage; D014182:Transplantation, Autologous; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D003561:Cytarabine; D011344:Procarbazine; D000069283:Rituximab; D014750:Vincristine; D003520:Cyclophosphamide; D013852:Thiotepa; D002066:Busulfan; D008727:Methotrexate