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

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.