A randomized study of autologous bone marrow-derived stem cells in pediatric cardiomyopathy

Bone marrow mononuclear cell fraction has been used as therapy for dilated cardiomyopathy in adults. Although case series are reported, there are no randomized controlled studies in children.

We designed a randomized, crossover, controlled pilot study to determine safety and feasibility of intracoronary stem cell therapy in children. The primary safety end-point was freedom from death and transplantation or any complication that could be considered related to bone marrow injection or anesthesia (e.g., infection, malignancy, anaphylaxis, renal deterioration). Other end-points were magnetic resonance imaging measurements and N-terminal prohormone brain natriuretic peptide. Participants included 10 children (mean age 7.2 years; range, 2.2-14.1 years; 6 boys) with cardiomyopathy (New York Heart Association/Ross Classification II-IV). Patients were crossed over at 6 months.

The original protocol was completed by 9 patients. The safety end-point was achieved in all. Ratio of the geometric means for treatment effect adjusting for baseline was assessed for end-diastolic and end-systolic volumes (EDV, ESV): 0.93 for EDV (95% confidence interval 0.88-0.99, p = 0.01), indicating EDV was on average 7% lower in patients after stem cell treatment, and 0.90 for ESV (95% confidence interval 0.82-1.00, p = 0.05), indicating ESV was on average 10% lower after stem cell treatment compared with placebo. The primary efficacy end-point ejection fraction was not met.

Bone marrow mononuclear cell therapy for cardiomyopathy is feasible and safe in children. Left ventricular volumes were significantly reduced 6 months after stem cell injection compared with placebo, which may reflect reverse remodeling.