Abstract:
BACKGROUND:Several lines of evidence suggest a T cell-mediated immune response in paraneoplastic neurological syndromes with anti-Hu antibodies (Hu-PNS). In order to investigate whether suppression of T cell-mediated immune responses in Hu-PNS patients improved their neurological outcome, we performed a prospective open-label, single-arm study on sirolimus. METHODS:Seventeen progressive Hu-PNS patients were treated with sirolimus with an intended treatment duration of 8 weeks. Primary outcome measures were (i) functional improvement, defined as a decrease of one or more points on the modified Rankin Scale (mRS), and (ii) improvement of neurological impairment, defined as an increase of one or more points on the Edinburgh Functional Impairment Tests (EFIT). RESULTS:One patient showed improvement on both clinical scales (mRS and EFIT). This patient presented with limbic encephalitis and improved dramatically from an mRS score of 3 to mRS 1. Another patient, with subacute sensory neuronopathy, remained stable at mRS 2 and improved one point on the EFIT scale. The other patients showed no improvement on the primary outcome measures. Median survival was 21 months. CONCLUSION:We conclude that treatment of Hu-PNS patients with sirolimus may improve or stabilize their functional disabilities and neurological impairments. However, the effects of this T cell-targeted therapy were not better than reported in trials on other immunotherapies for Hu-PNS. Trial Registration https://www.clinicaltrialsregister.eu/ctr-search/trial/2008-000793-20/NL.
journal_name
Neuro Oncoljournal_title
Neuro-oncologyauthors
de Jongste AH,van Gelder T,Bromberg JE,de Graaf MT,Gratama JW,Schreurs MW,Hooijkaas H,Sillevis Smitt PAdoi
10.1093/neuonc/nou126subject
Has Abstractpub_date
2015-01-01 00:00:00pages
145-50issue
1eissn
1522-8517issn
1523-5866pii
nou126journal_volume
17pub_type
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