Abstract 12754: Infused CD34 Cell Dose, not Bone Marrow CD34+ Cell Content, Improves Clinical Outcomes and LVEF in Patients With Left Ventricular Dysfunction post STEMI: Results of the PreSERVE-AMI Trial

Abstract

Background: Prior studies suggest an association between naturally high circulating levels of CD34+ cells (CD34) and better outcomes following ischemic events. Pts in the treatment arm of the PreSERVE-AMI study were infused with all CD34 yielded from their bone marrow harvest, resulting in pts with naturally higher CD34 cell counts being infused with a higher cell dose. To determine whether selection bias may have influenced results, we performed an analysis of the relationship between BM CD34 content and outcomes in PreSERVE-AMI. Methods: PreSERVE-AMI is a Phase 2, randomized, double-blind, placebo-controlled trial of autologous, BM derived CD34 (CLBS10) in pts with LV dysfunction (LVEF ≤48% by MRI) ≥4 days post-STEMI. All pts underwent mini BM harvest and were randomized 1:1 to intracoronary infusion of CD34 (minimum dose 10M±20% cells) or placebo (cell diluent). Primary safety endpoints included AEs, SAEs and MACE (CV mortality, HF hospitalization, reinfarction, revascularization). Secondary endpoints included LVEF change from baseline. Regression analyses were performed to assess the influence of BM CD34 content on outcomes. Results: 161 patients were randomized and received intracoronary infusion (Jan 2013-Dec 2014). Mean age was 57±10 and 82% were men. Mean follow-up time was 18 mo, and safety data are accruing. BM CD34 content was not associated with differences in baseline characteristics with the exception of diabetes prevalence being higher in those with higher BM CD34 count (p=0.03). In controls, regression analyses showed no association of BM CD34 content with rates of MACE (p=0.2), SAEs (p=0.4), or change in LVEF (p=0.9). However, in CD34 treated pts, there was a dose-dependent improvement in LV function (p=0.045) and dose-dependent trends in MACE and SAE reduction compared to controls. As previously reported SPECT perfusion improved to a similar degree in control and treated pts. Conclusions: These data suggest that intracoronary infusion of CD34 cells, rather than BM CD34 cell content, is responsible for the benefit observed in the CD34 treatment group. The finding of a dose-response relationship is an important advance for defining the CD34 as an active agent for tissue repair. Future studies will further define CD34 dosimetry.

CD34 positive cells as endothelial progenitor cells in biology and medicine

“…The PreSERVE-AMI was the largest randomized phase II trial that used autologous BM-CD34 + cell transplantation of LV dysfunction post-STEMI. After 12 months, transplanted subjects showed decreased infarct size, hospitalized days, and mortality compared to the non-treated group and increased LVEF in a dose-dependent manner, providing additional proof of the immunity and efficiency of CD34 + therapy in STEMI subjects ( Quyyumi et al, 2017 ). Besides, Poglajen et al demonstrated potential antiarrhythmic benefits of autologous G-CSF mobilized CD34 + cells on ventricular arrhythmias subjects ( Poglajen et al, 2019 ).…”

Healing the Ischaemic Heart: A Critical Review of Stem Cell Therapies

“…This study demonstrated a significant improvement in left ventricular ejection fraction (LVEF) in the treatment group [ 95 ]. The PreSERVE-AMI study was a phase II study in which autologous purified cells (a subset of BMCs) or a control were administered via intra-coronary infusion to STEMI patients [ 96 ]. After one year, while adjusting for the duration of ischaemia a dose-dependent improvement was observed in LVEF, infarct size and survival—suggesting purified cells may have beneficial effects on the ischaemic heart.…”