Phase I Study of Intravenous Low-dose Granulocyte Colony-stimulating Factor in Acute and Subacute Ischemic Stroke

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 mu g/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/mu L. 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/mu L at 150 and 300 mu g G-CSF/body/day, but rose above 40,000/mu L at 450 mu g 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 mu g/body/day) was safe and well tolerated in ischemic stroke patients, and leukocyte levels remained below 40,000/mu L.