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

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.

• Authors: Kai C Wollert, Gerd P Meyer, Jochen Müller-Ehmsen, Carsten Tschöpe, Vernon Bonarjee, Alf Inge Larsen, Andreas E May, Klaus Empen, Emmanuel Chorianopoulos, Ulrich Tebbe, Johannes Waltenberger, Heiko Mahrholdt, Benedikta Ritter, Jens Pirr, Dieter Fischer, Mortimer Korf-Klingebiel, Lubomir Arseniev, Hans-Gert Heuft, Jan E Brinchmann, Diethelm Messinger, Bernd Hertenstein, Arnold Ganser, Hugo A Katus, Stephan B Felix, Meinrad P Gawaz, Kenneth Dickstein, Heinz-Peter Schultheiss, Dennis Ladage, Simon Greulich, Johann Bauersachs
• Journal: European heart journal (Eur Heart J) Vol. 38 Issue 39 Pg. 2936-2943 (Oct 14 2017) ISSN: 1522-9645 [Electronic] England
• PMID: 28431003 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: [email protected].

Topics

• 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)