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.

Figures

Figure 1

Cerebrospinal fluid (CSF) white blood cell (WBC) count correlates with onset of neurologic symptoms and treatment with tacrolimus. The CSF WBC counts of 2 patients with Yo antibodies with ovarian cancer are shown in the context of neurologic symptom development (triangles) and tacrolimus treatment duration (shaded areas) (A and B). The first CSF sample was obtained approximately 1 week prior to the onset of treatment (B).

Figure 2

Kaplan-Meier survival curves. A, From time of diagnosis of paraneoplastic neurologic disorder. B, From start time of tacrolimus treatment. The dotted lines indicate 95% confidence intervals; the tick marks, censored patients; and the solid line, the survival curve.