title: Cellular immune suppression in paraneoplastic neurologic syndromes targeting intracellular antigens.
abstract: BACKGROUND Tumor treatment is the mainstay of therapy for paraneoplastic neurologic disorders (PNDs), but it is only effective in some cases and other treatment options are limited. OBJECTIVE To evaluate the short-term use of a combination of prednisone and tacrolimus for acute neurologic worsening in PND in which intracellular antigens are targeted. DESIGN Retrospective single-center case series of patients with PND treated with tacrolimus. SETTING The Rockefeller University Hospital, a research hospital in New York, New York. PATIENTS Twenty-six patients with PND with high titer (≥1:1000) anti-HuD, anti-Yo, or anti-CRMP5 autoantibodies were enrolled. Patients were referred from Memorial Sloan Kettering Cancer Center or self-referred. Two patients discontinued intervention owing to adverse events. INTERVENTIONS Patients were treated with tacrolimus, 0.15-0.30 mg/kg per day, in 2 divided oral doses with 60 mg per day of oral prednisone, tapered off during 1 to 4 weeks. MAIN OUTCOME MEASURES The primary outcome measure was median survival. Neurologic examinations before and after treatment as well as adverse events are described. RESULTS Median survival time was 52 months from time of diagnosis. Some patients experienced neurologic improvement that was functionally meaningful. The incidence of adverse events was similar to that generally reported with tacrolimus. CONCLUSIONS A short course of prednisone and tacrolimus to target central nervous system T cells in patients with PND with acute neurologic decline in which intracellular antigens are targeted was well tolerated and warrants further study. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00378326.
authors.affiliation: The Rockefeller University, 1230 York Ave, New York, NY 10065, USA.
authors.forename: Dana
authors.initials: D
authors.lastname: Orange
authors.forename: Mayu
authors.initials: M
authors.lastname: Frank
authors.forename: Suyan
authors.initials: S
authors.lastname: Tian
authors.forename: Athanasios
authors.initials: A
authors.lastname: Dousmanis
authors.forename: Ronen
authors.initials: R
authors.lastname: Marmur
authors.forename: Noreen
authors.initials: N
authors.lastname: Buckley
authors.forename: Salina
authors.initials: S
authors.lastname: Parveen
authors.forename: Jerome J
authors.initials: JJ
authors.lastname: Graber
authors.forename: Nathalie
authors.initials: N
authors.lastname: Blachère
authors.forename: Robert B
authors.initials: RB
authors.lastname: Darnell
mesh_terms: D000328:Adult; D000368:Aged; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D020361:Paraneoplastic Syndromes, Nervous System / Q000188:drug therapy* / Q000401:mortality; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use*; D012189:Retrospective Studies; D015996:Survival Rate; D016559:Tacrolimus / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D011241:Prednisone; D016559:Tacrolimus