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In a field characterized by mixed results and variable protocols, a large meta-analysis shows that transplantation of adult bone marrow cells (BMC) in patients with ischemic heart disease offers lasting improvements in key cardiac metrics compared with standard therapy alone. The study, published online June 22, 2012, ahead of print in Circulation, also suggests that the experimental treatment improves clinical outcomes.

Researchers led by Buddhadeb Dawn, MD, of the University of Kansas Medical Center and Hospital (Kansas City, KS), analyzed 50 studies (36 randomized controlled trials and 14 cohort studies) that were identified by database searches through January 2012. The studies involved 2,625 patients who either experienced an MI or had chronic ischemic heart disease.

Compared with standard treatment, BMC transplantation resulted in improvements in mean LVEF, infarct size, LV end-systolic volume, and LV end-diastolic volume (table 1).

Table 1. Cardiac Parameters: BMC Transplantation vs. Standard Therapy

The effect on LVEF persisted for at least 24 months after transplantation, while the improvements in the other cardiac parameters lasted for at least 12 months.

Substantial benefits were also seen in several clinical outcomes, including all-cause mortality, cardiac mortality, recurrent MI, and stent thrombosis (table 2).

Table 2. Clinical Outcomes: BMC Transplantation vs. Standard Therapy

In addition, strong trends emerged toward decreased risk of heart failure and cerebrovascular events. Safety measures including in-stent restenosis, TVR, and ventricular arrhythmias were similar between BMC therapy and controls

Basis for Larger Trials

The authors noted that the individual trials analyzed were not designed to assess long-term clinical outcomes but concluded that “these findings are highly significant from a therapeutic standpoint and provide a strong basis for large-scale clinical trials.”

In an e-mail communication, Dr. Dawn told TCTMD that this is the largest meta-analysis on the topic by far. “We can say with reasonable confidence that the observed effects are real and generally applicable to patient populations,” he said.

The authors acknowledge that the increase in LVEF imparted by BMC therapy is relatively small. On the other hand, the improvement in postinfarct remodeling may translate into superior long-term prognosis, they say. The mechanisms behind the reduction in infarct size and remodeling benefits remain poorly understood but could be due to enhanced angiogenesis and reduction in programmed cell death.

Dr. Dawn stressed that the survival benefit seen in this analysis is a critical basis for beginning large randomized trials of BMC transplantation, and the durability of positive effects add to the existing knowledge base on this topic. “It has been suggested that the effects of bone marrow cell therapy are short lasting,” he said. “[But] our results from pooled data show that these effects generally persist for longer periods.”

Another key finding is that benefits appear greater in patients who received bone marrow mononuclear cells than in those who received specific bone marrow subfractions, Dr. Dawn added.

As with any meta-analysis, the reliability of results from a pooled group of studies is up for debate. The authors note that the heterogeneity of the studies included limits the analysis. For example, there were wide differences with regard to imaging modalities used, timing and route of cell injection, and population characteristics. Still, the strong results in favor of BMC transplantation suggest more research is now warranted to rigorously evaluate the therapy, they conclude.

Study Details

Studies ranged in size from 10 to 391 patients, with a median sample size of 39 patients. Follow-up varied from 3 to 60 months, with a median duration of 6 months. Timing of transplantation in acute MI patients ranged from 1 day to 18.4 days, with a median delay of 6.7 days. All of the cohort studies and at least 15 of the randomized controlled trials failed to blind participants or the caregivers involved.

Related Stories:

• Stem Cell Therapy Fails to Show Benefit in Chronic Ischemic Heart Failure
• Bone Marrow Stem Cells Show Positive Results in Small Chronic AMI Trial
• Bone Marrow Cell Injection Promising for Chronic Ischemia

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