Effect of Progenitor Cell Mobilization With Granulocyte-Macrophage Colony-Stimulating Factor in Patients With Peripheral Artery Disease: A Randomized Clinical Trial

Study Questions:

What is the effect of therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF) on exercise capacity in patients with intermittent claudication?


In a phase 2 double-blind, placebo-controlled study, 159 patients (median [standard deviation] age, 64 [8] years; 87% male, 37% with diabetes) with intermittent claudication were enrolled at medical centers affiliated with Emory University in Atlanta, GA, between January 2010 and July 2012. Participants were randomized (1:1) to receive 4 weeks of subcutaneous injections of GM-CSF (leukine), 500 μg/day 3 times a week, or placebo. Both groups were encouraged to walk to claudication daily. The primary outcome was peak treadmill walking time (PWT) at 3 months. Secondary outcomes were PWT at 6 months and changes in circulating bone marrow progenitor cell (PC) levels, ankle-brachial index (ABI), and walking impairment questionnaire (WIQ) and 36-item Short-Form Health Survey (SF-36) scores.


Of the 159 patients randomized, 80 were assigned to the GM-CSF group. The mean (SD) PWT at 3 months increased in the GM-CSF group from 296 (151) seconds to 405 (248) seconds (mean change, 109 seconds [95% confidence interval (CI), 67-151]), and in the placebo group from 308 (161) seconds to 376 (182) seconds (change of 56 seconds [95% CI, 14-98]), but this difference was not significant (mean difference in change in PWT, 53 seconds [95% CI, −6 to 112], p = 0.08). At 3 months, compared with placebo, GM-CSF improved the physical functioning subscore of the SF-36 questionnaire by 11.4 (95% CI, 6.7-16.1) versus 4.8 (95% CI, −0.1 to 9.6), with a mean difference in change for GM-CSF versus placebo of 7.5 (95% CI, 1.0-14.0; p = 0.03). Similarly, the distance score of the WIQ improved by 12.5 (95% CI, 6.4-18.7) versus 4.8 (95% CI, −0.2 to 9.8) with GM-CSF compared with placebo (mean difference in change, 7.9 [95% CI, 0.2-15.7], p = 0.047). There were no significant differences in the ABI, WIQ distance and speed scores, claudication onset time, or mental or physical component scores of the SF-36 between the groups.


The authors concluded that therapy with GM-CSF 3 times a week did not improve treadmill walking performance at the 3-month follow-up.


In this phase 2 study, after administration of a myeloid cytokine that mobilizes bone marrow PCs into the circulation, there was no difference in PWT between the GM-CSF and placebo groups. In secondary analyses, there was improvement in the SF-36 physical functioning score and the WIQ distance score with GM-CSF as compared with placebo. However, there were no significant differences between the intervention and placebo groups with regard to change in WIQ walking speed or stair-climbing score, COT, PCS-36 or MCS-36 components of the SF-36, ABI, or oxygen consumption. The improvement in some secondary outcomes observed with GM-CSF suggests that GM-CSF may warrant further study in patients with claudication, but overall, the results are disappointing. Additional research is also indicated to investigate the variability of responsiveness to GM-CSF and its clinical implications.

Clinical Topics: Vascular Medicine, Atherosclerotic Disease (CAD/PAD)

Keywords: Granulocyte-Macrophage Colony-Stimulating Factor, Peripheral Arterial Disease

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