title: Potential of chemo-immunotherapy and radioimmunotherapy in relapsed primary central nervous system (CNS) lymphoma.
abstract: Five patients with relapsed PCNSL were given chemo-immunotherapy (rituximab followed by carboplatin and methotrexate) with osmotic blood-brain barrier (BBB) opening. Four patients achieved CR and one patient had stable disease. Two patients (2/5) had durable responses (survival: 230+, 122+, 82, 42, 38 weeks). One patient later received Indium-111-ibritumomab tiuxetan and Yttrium-90-ibritumomab tiuxetan intravenous, without BBB opening. There was good uptake of Indium-111 ibritumomab tiuxetan in tumor on SPECT scan after 48 h. Estimated radiation doses to brain around and distant from tumor were within safe limits. After Ytrium-90 ibritumomab tiuxetan there was CR in enhancing tumor where the BBB was leaky, but lesions occurred in other brain regions, where the BBB was intact during Yttrium-90 ibritumomab tiuxetan infusion. Imaging and dosimetry with Indium-111 ibritumomab tiuxetan and efficacy with Yttrium-90 ibritumomab tiuxetan suggest the need for future enhanced CNS delivery when using monoclonal or radiolabeled antibodies, as intravenous delivery alone may provide modest clinical benefit due to limited BBB permeability.
authors.affiliation: Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Doolittle
authors.forename: Kristoph
authors.initials: K
authors.lastname: Jahnke
authors.forename: Richard
authors.initials: R
authors.lastname: Belanger
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Ryan
authors.forename: Robert W
authors.initials: RW
authors.lastname: Nance
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Lacy
authors.forename: Rose Marie
authors.initials: RM
authors.lastname: Tyson
authors.forename: Marianne
authors.initials: M
authors.lastname: Haluska
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Hedrick
authors.forename: Csanad
authors.initials: C
authors.lastname: Varallyay
authors.forename: Edward A
authors.initials: EA
authors.lastname: Neuwelt
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001812:Blood-Brain Barrier; D001932:Brain Neoplasms / Q000628:therapy*; D016190:Carboplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007205:Indium Radioisotopes / Q000627:therapeutic use; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D016499:Radioimmunotherapy; D015021:Yttrium Radioisotopes / Q000627:therapeutic use*