title: High-dose methotrexate with R-CHOP therapy for the treatment of patients with primary central nervous system lymphoma.
abstract: We describe MR-CHOP therapy, a novel treatment regimen consisting of high-dose methotrexate and R-CHOP that provides systemic anti-tumor activity with penetration of the blood-brain barrier in patients with newly diagnosed primary central nervous system lymphoma. The MR-CHOP regimen was administered with 2 g/m(2) of methotrexate and 375 mg/m(2) of rituximab on day 1, 750 mg/m(2) of cyclophosphamide on day 3, 50 mg/m(2) of doxorubicin on day 3, 1.4 mg/m(2) of vincristine on day 3 and 100 mg of prednisolone on days 1-5 in this pilot study of seven patients. Six cycles of MR-CHOP therapy were administered every 3 weeks, followed by high-dose chemotherapy with stem cell rescue in young patients, or an additional two cycles of 4 g/m(2) methotrexate and rituximab in older patients. The overall response rate was 100%, with 85.7% complete remission (CR). One patient showed partial response, relapsed and subsequently died. Another relapsed following CR, and was rescued by further salvage therapy. The others survive without relapse at a median observation period of 24 months. Hematological toxicity included grade 4 leukocytopenia in 4/7 and neutropenia in 5/7, which were transient and tolerated well. Non-hematological toxicities were tolerated well. The efficacy of this novel regimen as remission induction therapy was found to be promising in this pilot study, although the number of patients was small and follow-up short.
authors.affiliation: Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, 920-0293, Japan. yasum@kanazawa-med.ac.jp.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Masaki
authors.affiliation: Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, 920-0293, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Miki
authors.affiliation: Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, 920-0293, Japan.
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, 920-0293, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, 920-0293, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Iwao
authors.affiliation: Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, 920-0293, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Nakajima
authors.affiliation: Department of Pathology and Laboratory Medicine, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, 920-0293, Japan.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Kurose
authors.affiliation: Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, 920-0293, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Sakai
authors.affiliation: Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, 920-0293, Japan.
authors.forename: Zhe-Xiong
authors.initials: ZX
authors.lastname: Jin
authors.affiliation: Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, 920-0293, Japan.
authors.forename: Toshioki
authors.initials: T
authors.lastname: Sawaki
authors.affiliation: Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, 920-0293, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Kawanami
authors.affiliation: Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, 920-0293, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Fujita
authors.affiliation: Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, 920-0293, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, 920-0293, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Fukushima
authors.affiliation: Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, 920-0293, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hirose
authors.affiliation: Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, 920-0293, Japan.
authors.forename: Hisanori
authors.initials: H
authors.lastname: Umehara
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*; D016543:Central Nervous System Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008223:Lymphoma / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008279:Magnetic Resonance Imaging; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D012189:Retrospective Studies; D000069283:Rituximab; D016019:Survival Analysis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D008727:Methotrexate