Phase I study of intravenous low-dose granulocyte colony-stimulating factor in acute and subacute ischemic stroke.

Abstract

BACKGROUND Granulocyte colony-stimulating factor (G-CSF; filgrastim) may be useful for the treatment of acute ischemic stroke because of its neuroprotective and neurogenesis-promoting properties, but an excessive increase of neutrophils may lead to brain injury. We examined the safety and tolerability of low-dose G-CSF and investigated the effectiveness of G-CSF given intravenously in the acute phase (at 24 hours) or subacute phase (at 7 days) of ischemic stroke. METHODS Three intravenous dose regimens (150, 300, or 450 μg/body/day, divided into 2 doses for 5 days) of G-CSF were examined in 18 patients with magnetic resonance imaging (MRI)-confirmed infarct in the territory of the middle cerebral artery. Nine patients received the first dose at 24 hours poststroke (acute group) and 9 patients received the first dose on day 7 poststroke (subacute group; n = 3 at each dose in each group). A scheduled administration of G-CSF was skipped if the patient's leukocyte count exceeded 40,000/μL. Patients received neurologic and MRI examinations. RESULTS We found neither serious adverse event, drug-related platelet reduction nor splenomegaly. Leukocyte levels remained below 40,000/μL at 150 and 300 μg G-CSF/body/day, but rose above 40,000/μL at 450 μg G-CSF/body/day. Neurologic function improvement between baseline and day 90 was more marked after treatment in the acute phase versus the subacute phase (Barthel index 49.4 ± 28.1 v 15.0 ± 22.0; P < .01). CONCLUSIONS Low-dose G-CSF (150 and 300 μg/body/day) was safe and well tolerated in ischemic stroke patients, and leukocyte levels remained below 40,000/μL.

DOI: 10.1016/j.jstrokecerebrovasdis.2012.08.002

Cite this paper

@article{Moriya2013PhaseIS, title={Phase I study of intravenous low-dose granulocyte colony-stimulating factor in acute and subacute ischemic stroke.}, author={Yusuke Moriya and Atsushi Mizuma and Tsuyoshi Uesugi and Yoichi Ohnuki and Eiichiro Nagata and Wakoh Takahashi and Hiroyuki Kobayashi and Hiroshi Kawada and Kiyoshi Ando and Shigeharu Takagi and Shunya Takizawa}, journal={Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association}, year={2013}, volume={22 7}, pages={1088-97} }