By Alexander E. Merkler, MD, MS
Assistant Professor of Neurology and Neuroscience, Weill Cornell Medical College
This study proposes that autologous bone marrow mononuclear intravenous infusion for severe traumatic brain injury in children appears safe and potentially may be efficacious.
Cox CS Jr, Notrica DM, Juranek J, et al. Autologous bone marrow mononuclear cells to treat severe traumatic brain injury in children. Brain 2024;147:1914-1925.
Pediatric traumatic brain injury is a leading cause of morbidity and mortality in children. Each year more than 1 million children sustain a traumatic brain injury. Treatment consists of surgery and medical management to prevent secondary injury, but many patients remain with lifelong disability. Novel therapies are necessary to reduce secondary injury and improve functional outcomes.
In this Phase II, two-center, randomized, double-blind, placebo-sham-controlled Bayesian dose-escalation clinical trial, patients aged 5-17 years with severe traumatic brain injury (initial Glasgow Coma Scale score ≤ 8) were randomized to autologous bone marrow mononuclear cells (BMMNCs) or placebo in a 3:2 ratio. Bone marrow harvesting was performed within 48 hours of injury and then intravenously infused. The primary outcome was quantitative brain volumes using advanced magnetic resonance imaging (MRI) and microstructural integrity of the corpus callosum at six and 12 months. In addition, the authors evaluated safety and long-term functional outcomes.
The authors randomized 47 patients, of which 37 completed one-year follow-up (23 BMMNC, 14 placebo). White matter volume at one year was significantly preserved in the BMMNC group vs. the placebo group (P = 0.01), and there was a trend to preservation of corpus callosum integrity (P = 0.055). Regarding safety, one patient in the BMMNC group died before the one-month follow-up visit because of sepsis. The authors found no clear reduction of intensive care unit days, ventilator days, or intracranial pressure monitoring days.
The authors acknowledged the small sample size and potential confounders regarding the effect of resuscitation on traumatic brain injury outcomes. The authors concluded that the next step is a Phase III trial with Glasgow Coma Scale scores as a primary outcome.
COMMENTARY
This study represents a novel therapy for severe traumatic brain injury, a disease in which there have been few therapeutic advances over the last decades. BMMNC appeared generally safe and showed promise regarding mitigation of secondary brain injury via MRI. However, the number of patients enrolled was small, and one patient who received BMMNC had sepsis and died. The results should be considered thought-provoking, but further studies are necessary to evaluate the utility of BMMNC.
