title: High-dose methotrexate following intravitreal methotrexate administration in preventing central nervous system involvement of primary intraocular lymphoma.
abstract: In order to prevent central nervous system (CNS) involvement and improve the prognosis of primary intraocular lymphoma (PIOL), we prospectively evaluated the efficacy of combined therapy using intravitreal methotrexate (MTX) and systemic high-dose MTX on treatment-naïve PIOL. Patients with newly diagnosed PIOL whose lymphoma was limited to the eyes were enrolled. The patients were treated with weekly intravitreal MTX until the ocular lesions were resolved, followed by five cycles of systemic high-dose MTX (3.5 g/m2) every other week. Ten patients were enrolled in this study and completed the treatment. All patients achieved complete response for their ocular lesions with rapid decrease of intravitreal interleukin-10 concentration. Adverse events of intravitreal and systemic high-dose MTX were mild and tolerable. With a median follow-up of 29.5 months, four patients (40%) experienced the CNS disease development and the mean CNS lymphoma-free survival (CLFS) time was 51.1 months. Two-year CLFS, which was the primary end-point of the study, was 58.3% (95% confidence interval, 23.0-82.1%). In contrast, eight patients were treated with intravitreal MTX alone in our institute, and their 2-year CLFS was 37.5% (95% confidence interval, 8.7-67.4%). In conclusion, systemic high-dose MTX following intravitreal MTX is feasible and might be effective in preventing CNS involvement of PIOL. Further arrangements are worth considering in order to improve the effects. This study was registered with UMIN Clinical Trials Registry (UMIN000003921).
authors.affiliation: Department of Hematology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Akiyama
authors.affiliation: Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takase
authors.affiliation: Department of Internal Medicine, Tokyo Adventist Hospital, Tokyo, Japan.
authors.forename: Fumito
authors.initials: F
authors.lastname: Kubo
authors.affiliation: Department of Internal Medicine, Flowers and Forest Tokyo Hospital, Tokyo, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Miki
authors.affiliation: Department of Hematology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Masahide
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Clinical Research Center, Medical Hospital of Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tomita
authors.affiliation: Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Mochizuki
authors.affiliation: Department of Hematology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Miura
authors.affiliation: Department of Hematology, Tokyo Medical and Dental University, Tokyo, Japan. ara.hema@tmd.ac.jp.
authors.forename: Ayako
authors.initials: A
authors.lastname: Arai
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D015415:Biomarkers; D016543:Central Nervous System Neoplasms / Q000401:mortality / Q000517:prevention & control* / Q000556:secondary*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D064090:Intraocular Lymphoma / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D058449:Intravitreal Injections; D053208:Kaplan-Meier Estimate; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D015415:Biomarkers; D016207:Cytokines; D008727:Methotrexate
keywords: Central nervous system disease; interleukin-10; intraocular lymphoma; methotrexate; uveitis