Colony stimulating factors (including erythropoietin, granulocyte colony stimulating factor and analogues) for stroke

Background Colony stimulating factors (CSFs), also called haematopoietic growth factors, regulate bone marrow production of circulating red and white cells, and platelets. They have been shown to be neuroprotective in experimental stroke. Some CSFs also mobilise the release of bone marrow stem cells into the circulation. Objectives To assess the effects of CSFs on functional outcome and haematology measures in patients with acute or subacute stroke. Search strategy We searched the Cochrane Stroke Group Trials Register (last searched November 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2006), MEDLINE (1985 to June 2006), EMBASE (1985 to June 2006), and Science Citation Index (1985 to June 2006). In an attempt to identify further published, unpublished and ongoing trials we contacted manufacturers and principal investigators of trials (last contacted 2006). We also searched reference lists of relevant articles and reviews. Selection criteria Unconfounded randomised controlled trials recruiting patients with acute or subacute ischaemic or haemorrhagic stroke were included. CSFs included stem cell factor (SCF), erythropoietin (EPO), granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), macrophage-colony stimulating factor (M-CSF, CSF-1), and thrombopoietin (TPO), or analogues of these. The primary outcome was functional outcome (assessed as combined death or disability and dependency using scales such as the modified Rankin Scale or Barthel Index) at the end of the trial. Secondary outcomes included safety at the end of treatment (death, impairment, deterioration, extension or recurrence), death at the end of follow up, and haematology measures (blood counts at or around day seven after treatment commenced). Data collection and analysis Two review authors independently extracted data and assessed trial quality. Study authors were contacted for additional information. Main results No large trials were identified. EPO therapy was associated with a non-significant reduction in neurological impairment in one small trial (n = 40 participants) but had no significant effect on haematological measures. G-CSF was associated with a non-significant reduction in combined death and dependency in two small trials (n = 46 participants) although there was substantial heterogeneity in this result. G-CSF significantly elevated white cell count in three trials (n = 91). Further small trials of EPO and G-CSF are ongoing. Authors' conclusions No large trials of EPO, G-CSF or other colony stimulating factors have been performed and it is too early to know whether CSFs improve functional outcome.