Intracoronary autologous bone marrow cell transfer after myocardial infarction: the BOOST-2 randomised placebo-controlled clinical trial

Eur Heart J. 2017 Oct 14;38(39):2936-2943. doi: 10.1093/eurheartj/ehx188.

Abstract

Aims: Intracoronary infusion of autologous nucleated bone marrow cells (BMCs) enhanced the recovery of left ventricular ejection fraction (LVEF) after ST-segment elevation myocardial infarction (STEMI) in the randomised-controlled, open-label BOOST trial. We reassessed the therapeutic potential of nucleated BMCs in the randomised placebo-controlled, double-blind BOOST-2 trial conducted in 10 centres in Germany and Norway.

Methods and results: Using a multiple arm design, we investigated the dose-response relationship and explored whether γ-irradiation which eliminates the clonogenic potential of stem and progenitor cells has an impact on BMC efficacy. Between 9 March 2006 and 16 July 2013, 153 patients with large STEMI were randomly assigned to receive a single intracoronary infusion of placebo (control group), high-dose (hi)BMCs, low-dose (lo)BMCs, irradiated hiBMCs, or irradiated loBMCs 8.1 ± 2.6 days after percutaneous coronary intervention (PCI) in addition to guideline-recommended medical treatment. Change in LVEF from baseline (before cell infusion) to 6 months as determined by MRI was the primary endpoint. The trial is registered at Current Controlled Trials (ISRCTN17457407). Baseline LVEF was 45.0 ± 8.5% in the overall population. At 6 months, LVEF had increased by 3.3 percentage points in the control group and 4.3 percentage points in the hiBMC group. The estimated treatment effect was 1.0 percentage points (95% confidence interval, -2.6 to 4.7; P = 0.57). The treatment effect of loBMCs was 0.5 percentage points (-3.0 to 4.1; P = 0.76). Likewise, irradiated BMCs did not have significant treatment effects. BMC transfer was safe and not associated with adverse clinical events.

Conclusion: The BOOST-2 trial does not support the use of nucleated BMCs in patients with STEMI and moderately reduced LVEF treated according to current standards of early PCI and drug therapy.

Keywords: Bone marrow cell therapy; Cardiac magnetic resonance imaging; Randomized placebo-controlled trial; ST-segment elevation myocardial infarction.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Bone Marrow Cells / radiation effects
  • Bone Marrow Transplantation / methods*
  • Double-Blind Method
  • Female
  • Gamma Rays
  • Humans
  • Infusions, Intralesional
  • Magnetic Resonance Angiography
  • Male
  • Middle Aged
  • Percutaneous Coronary Intervention
  • ST Elevation Myocardial Infarction / therapy*
  • Stem Cell Transplantation / methods
  • Stem Cells / radiation effects
  • Transplantation, Autologous
  • Treatment Outcome
  • Ventricular Function, Left / physiology