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

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.